LIBRO - Shengmai San

Shengmai San
Traditional Herbal Medicines for Modern Times
Each volume in this series provides academia, health sciences and the herbal
medicines industry with in-depth coverage of the herbal remedies for infectious
diseases, certain medical conditions or the plant medicines of a particular country.
Edited by Dr Roland Hardman
Volume 1
Shengmai San, edited by Kam-Ming Ko
Shengmai San
Kam-Ming Ko, Hong Kong University of

Science & Technology, Kowloon, Hong Kong, China
London and New York

First published 2002 by Taylor & Francis
11 New Fetter Lane, London EC4P 4EE
Simultaneously published in the USA and Canada
by Taylor & Francis Inc,
29 West 35th Street, New York, NY 10001
Taylor & Francis is an imprint of the Taylor & Francis Group
This edition published in the Taylor & Francis e-Library, 2004.
© 2002 Taylor & Francis

All rights reserved. No part of this book may be reprinted or reproduced
or utilised in any form or by any electronic, mechanical, or other means,
now known or hereafter invented, including photocopying and recording,
or in any information storage or retrieval system, without permission in
writing from the publishers.
Every effort has been made to ensure that the advice and information in
this book is true and accurate at the time of going to press. However,
neither the publisher nor the authors can accept any legal responsibility or
liability for any errors or omissions that may be made. In the case of drug
administration, any medical procedure or the use of technical equipment
mentioned within this book, you are strongly advised to consult the
manufacturer’s guidelines.
British Library Cataloguing in Publication Data
A catalogue record for this book is available
from the British Library
Library of Congress Cataloging in Publication Data
A catalog record has been requested
ISBN 0-203-21645-8 Master e-book ISBN
ISBN 0-203-27265-X (Adobe eReader Format)

ISBN 0-415-28490-2 (Print Edition)
Contents
Contributors vii
Preface to the series ix
Preface xiii
1 Shengmai San – a renowned traditional Chinese medicinal formula 1

SONG-MING LIANG, SHU-YING CHEN, SI-QIAN LIANG
2 Pharmacological studies on Shengmai San 16

KAM-MING KO, DUNCAN H.F. MAK, TZE-KIN YIM AND YONG-QING YAN
3 Clinical studies on Shengmai San 41

YE-ZHI RONG, MEI-HUA ZHAO, BAO-JING LU, XIANG-YANG ZHU,
SHANG-BIAO LU, YA-CHEN ZHANG, JIE CHEN
4 Side effects of Shengmai San 78

ZHI-MIN XU AND YE-ZHI RONG
5 Phytochemistry and pharmacology of component herbs of

Shengmai San 82
SIU-PO IP, TIMOTHY C.M. TAM AND CHUN-TAO CHE
6 Contemporary applications of a traditional formula:

manufacture of Shengmai San (SMS) preparations and
their applications 112
LIANG-YUAN ZHENG
Glossary 126
Index 132
Contributors
Bao-Jing Lu Liang-Yuan Zheng

Department of Cardiology Livzon Pharmaceutical Group, Inc.
Xin-Hua Hospital North Guihua Road, Gongbei
Shanghai Second Medical University Zhuhai, Guangdong 519020
1665 Kong-Jiang Road China
Shanghai 200092
China Mei-Hua Zhao
Department of Cardiology
Chun-Tao Che Xin-Hua Hospital
School of Chinese Medicine Shanghai Second Medical University
The Chinese University of Hong Kong 1665 Kong-Jiang Road
Shatin, N.T. Shanghai 200092
Hong Kong China
China
Shang-Biao Lu
Duncan H.F. Mak
Department of Biochemistry
Xin-Hua Hospital
Hong Kong University of Science
Shanghai Second Medical University
& Technology
1665 Kong-Jiang Road
Clear Water Bay
Shanghai 200092
Hong Kong
China
China
Jie Chen Shu-Ying Chen
Department of Cardiology School of Materia Medica
Xin-Hua Hospital Guangzhou University of Traditional
Shanghai Second Medical University Chinese Medicine
1665 Kong-Jiang Road 12 Jichang Road, Guangzhou
Shanghai 200092 519020
China China
Kam-Ming Ko Si-Qian Liang

Department of Biochemistry Department of Applied Science
Hong Kong University of Science Hong Kong Institute of Vocational
& Technology Education (CW)
Clear Water Bay Chai Wan
Hong Kong Hong Kong
China China
viii Contributors
Siu-Po Ip Ya-Chen Zhang
School of Chinese Medicine Department of Cardiology
The Chinese University of Hong Kong Xin-Hua Hospital
Shatin, N.T. Shanghai Second Medical University
Hong Kong 1665 Kong-Jiang Road
China Shanghai 200092
China
Song-Ming Liang
School of Chinese Medicine Ye-Zhi Rong
The Chinese University of Hong Kong Dept. of Medicine, Xin-Hua Hospital
Shatin, N.T. Shanghai Second Medical University
Hong Kong 1665 Kong-Jiang Road
China Shanghai 200092
China
Timothy C.M. Tam
School of Pharmacy Yong-Qing Yan
The Chinese University of Hong Kong The China Pharmaceutical University
Shatin, N.T. 24 Tong Jia Xiang, Nanjin
Hong Kong Jiangsu 210009
China China
Tze-Kin Yim Zhi-Min Xu

Department of Biochemistry Department of Cardiology
Hong Kong University of Science & Xin-Hua Hospital
Technology Shanghai Second Medical University
Clear Water Bay 1665 Kong-Jiang Road
Hong Kong Shanghai 200092
China China
Xiang-Yang Zhu
Xin-Hua Hospital
Shanghai Second Medical University
1665 Kong-Jiang Road
Shanghai 200092
China
Preface to the series
Global warming and global travel are among the factors resulting in the spread of
such infectious diseases as malaria, tuberculosis, hepatitis B and HIV. All these are not
well controlled by the present drug regimes. Antibiotics too are failing because of
bacterial resistance. Formerly less well known tropical diseases are reaching new shores.
A whole range of illnesses, for example cancer, occur worldwide. Advances in molecular
biology, including methods of in vitro testing for a required medical activity give
new opportunities to draw judiciously upon the use and research of traditional herbal
remedies from around the world. The re-examining of the herbal medicines must be
done in a multidisciplinary manner.
Since 1997 twenty volumes have been published in the Book Series Medicinal and
Aromatic Plants – Industrial Profiles. The series continues, and is characterised by a
single plant genus per volume. With the same Series Editor, this new series Traditional
Herbal Medicines for Modern Times, covers multi genera per volume. It accom-
modates for example, the Traditional Chinese Medicines (TCM), the Japanese Kampo
versions of this and the Ayurvedic formulations of India. Collections of plants are also
brought together because they have been re-evaluated for the treatment of specific
diseases, such as malaria, tuberculosis, cancer, diabetes, etc. Yet other collections are of
the most recent investigations of the endemic medicinal plants of a particular country,
e.g. of India, South Africa, Mexico, Brazil (with its vast flora), or of Malaysia with its
rainforests said to be the oldest in the world.
Each volume reports on the latest developments and discusses key topics relevant
to interdisciplinary health science research by ethnobiologists, taxonomists, conserva-
tionists, agronomists, chemists, pharmacologists, clinicians and toxicologists. The Series
is relevant to all these scientists and will enable them to guide business, government
agencies and commerce in the complexities of these matters. The background to the
subject is outlined below.
Over many centuries, the safety and limitations of herbal medicines have been
established by their empirical use by the ‘healers’ who also took a holistic approach.
The ‘healers’ are aware of the infrequent adverse affects and know how to correct these
when they occur. Consequently and ideally, the pre-clinical and clinical studies of
a herbal medicine need to be carried out with the full cooperation of the traditional
healer. The plant composition of the medicine, the stage of the development of the
plant material, when it is to be collected from the wild or when from cultivation, its
post-harvest treatment, the preparation of the medicine, the dosage and frequency
and much other essential information is required. A consideration of the intellectual
property rights and appropriate models of benefit sharing may also be necessary.
x Preface to the series
Wherever the medicine is being prepared, the first requirement is a well docu-
mented reference collection of dried plant material. Such collections are encouraged by
organisations like the World Health Organisation and the United Nations Industrial
Development Organisation. The Royal Botanic Gardens at Kew in the UK is building
up its collection of traditional Chinese dried plant material relevant to its purchase and
use by those who sell or prescribe TCM in the UK.
In any country, the control of the quality of plant raw material, of its efficacy and of
its safety in use, are essential. The work requires sophisticated laboratory equipment
and highly trained personnel. This kind of ‘control’ cannot be applied to the locally
produced herbal medicines in the rural areas of many countries, on which millions of
people depend. Local traditional knowledge of the ‘healers’ has to suffice.
Conservation and protection of plant habitats is required and breeding for bio-
logical diversity is important. Gene systems are being studied for medicinal exploita-
tion. There can never be too many seed conservation ‘banks’ to conserve genetic
diversity. Unfortunately such banks are usually dominated by agricultural and horti-
cultural crops with little space for medicinal plants. Developments such as random
amplified polymorphic DNA enable the genetic variability of a species to be checked.
This can be helpful in deciding whether specimens of close genetic similarity warrant
storage.
From ancient times, a great deal of information concerning diagnosis and the use
of traditional herbal medicines has been documented in the scripts of China, India and
elsewhere. Today, modern formulations of these medicines exist in the form of e.g.
powders, granules, capsules and tablets. They are prepared in various institutions e.g.
government hospitals in China and Korea, and by companies such as Tsumura Co. of
Japan with good quality control. Similarly, products are produced by many other com-
panies in India, the USA and elsewhere with a varying degree of quality control. In
the USA, the dietary supplement and Health Education Act of 1994 recognised the
class of physiotherapeutic agents derived from medicinal and aromatic plants. Further-
more, under public pressure, the US Congress set up an Office of Alternative Medicine
and this office in 1994 assisted the filing of several Investigational New Drug (IND)
applications, required for clinical trials of some Chinese herbal preparations. The signific-
ance of these applications was that each Chinese preparation involved several plants
and yet was handled as a single IND. A demonstration of the contribution to efficacy, of
each ingredient of each plant, was not required. This was a major step forward towards
more sensible regulations with regard to phytomedicines.
Something of the subject of western herbal medicines is now being taught again
to medical students in Germany and Canada. Throughout Europe, the USA, Australia
and other countries, pharmacy and health related schools are increasingly offering
training in phytotherapy. TCM clinics are now common outside of China, and an
Ayurvedic Hospital now exists in London and a degree course in Ayurveda is also
available here.
The term ‘integrated medicine’ is now being used which selectively combines tradi-
tional herbal medicine with ‘modern medicine’. In Germany there is now a hospital
in which TCM is integrated with western medicine. Such co-medication has become
common in China, Japan, India, and North America by those educated in both systems.
Benefits claimed include improved efficacy, reduction in toxicity and the period of
medication, as well as a reduction in the cost of the treatment. New terms such as
adjunct therapy, supportive therapy and supplementary medicine now appear as a
Preface to the series xi
consequence of such co-medication. Either medicine may be described as an adjunct to
the other depending on the communicator’s view.
Great caution is necessary when traditional herbal medicines are used by those doctors
not trained in their use and likewise when modern medicines are used by traditional
herbal doctors. Possible dangers from drug interactions need to be stressed.
Dr Roland Hardman
January 2002
Preface
The practice of traditional Chinese medicine (TCM) commonly prescribes herbal formula
for the prevention and treatment of diseases. Shengmai San (SMS), a famous Chinese
medicinal formula that has been used for more than eight hundred years in China, is
comprised of Radix Ginseng, Fructus Schisandrae and Radix Ophiopogonis. Traditionally,
SMS is used for the treatment of excessive loss of essence Qi and body fluid that threaten
heart failure, particularly in summer when heat exhaustion and profuse sweating com-
monly occur. SMS, which can restore blood volume and prevent myocardial infarction,
is also prescribed contemporarily for patients with coronary heart disease and various
cardiovascular disorders. With the support from a number of experts involved in dif-
ferent areas of TCM, particularly the experimental and clinical research on SMS, this
book was compiled to provide a comprehensive treatise on the historical, phytochemical,
pharmacological/toxicological, clinical as well as pharmaceutical aspect of SMS and its
component herbs. This monograph therefore provides a scientific rationale of using
multi-component formulation in TCM for the prevention and treatment of diseases.
Kam-Ming Ko, Ph.D.

February 2001
A renowned TCM formula 1
1 Shengmai San – a renowned

traditional Chinese medicinal
formula
Song-Ming Liang, Shu-Ying Chen, Si-Qian
Liang [Translated by Kam-Ming Ko]
THE THEORY OF TRADITIONAL CHINESE MEDICINE

IN PRESCRIPTION
I. Treatment by differentiation of signs and symptoms

The basis of disease treatment in traditional Chinese medicine (TCM) emphasizes the
principle of ‘treatment by differentiation of signs and symptoms’, which requires the
identification of the etiology (causes of the symptoms), the definition of the therapeutic
principles, the prescription of medicinal formula and the choice of herbs.
The Differentiation of Signs and Symptoms is a know-how, based on various stages of
development of the disease, to analyze and diagnose in terms of syndromes. In other
words, it is a process in which the cause, pathogenesis, nature and location of a disease
is defined and served as the basis for ‘treatment’.
II. The eight therapeutic principles

‘Treatment’ is a process of applying therapeutic principles and herbal prescriptions to
rectify the abnormal body condition, based on information derived from the ‘differ-
entiation of symptoms’. Under the theory of TCM there are Eight Therapeutic Principles,
namely; diaphoresis, inducing emesis, purgation, reconciliation, warming, heat-clearing, resolution
and invigoration, each of which targets the Eight Principal Syndromes: Yin and Yang, super-
ficies and interior, cold and heat, deficiency (asthenia) and sthenia. Diaphoresis is a treatment
for expelling superficially located evils by opening pores of the skin, regulating the
function of Ying and Wei, and inducing perspiration. Emetic therapy is a treatment for
the elimination of harmful substances from the throat, esophagus and stomach by the
application of drug or physical stimuli that can induce vomiting. Purgation is a treat-
ment for eliminating undigested food, sthenic heat-evil and fluid by the application of
purgatives. Reconciliation is a treatment for regulating the cold and heat of the superficies
and interior, as well as coordinating the functions of the viscerae and organs. Warming
is a treatment for cold syndrome with medicine of a warm and hot nature. Heat-clearing
therapy is a treatment for clearing away the heat-evil with cold-natured drugs. Dispelling
therapy is a treatment for dissipating sthenic evils, such as stagnated energy, blood stasis,
phlegm-wetness and indigestion. Invigoration is treatment for various types of deficiency-
syndrome due to insufficiency of the Yin, Yang, Qi and Blood.
The Eight Therapeutic Principles have long been documented in the Canon of Internal
Medicine. However, it is not until the Qing dynasty that Cheng (1732) provided a
systematic evaluation and summary of the principles in his ‘Summary on Medicine from
2 Song-Ming Liang et al.
Clinical Practice’, which states that ‘diagnosis of diseases can be generalized into Yin and
Yang, superficies and interior, cold and heat, deficiency (asthenia) and sthenia, while treatment
can be fully effected by diaphoresis, inducing emesis, purgation, reconciliation, warming,
heat-clearing, resolution and invigoration.’ The Eight Therapeutic Principles should therefore
be applied on the ground of the Eight Principal Syndromes.
Although the Eight Therapeutic Principles have been tailored-made for the Eight
Principal Syndromes, clinical manifestation of diseases is usually complex and not readily
tackled by a single therapeutic method. A combination of a few therapeutic interven-
tions could assure a complete remedy for the condition. In fact, the effect of treatment
could be varied further by the priority as well as the extent of applying one or more of
the Eight Therapeutic Principles. Therefore, the clinical application of these therapeutic
methods should be based on the syndromes and the course of disease development
before coming up with the appropriate prescriptions.
The theory of TCM holds that treatment of diseases should be guided by the theory
and therapeutic principles, and implemented by applying formulas and herbs (or drugs).
This bespeaks much of the importance of the theoretical basis and therapeutic principles
for choosing the right formula and herbs for treatment. In TCM, the use of multi-
component prescriptions is far more common than single herb in the prevention and
treatment of diseases. Prescriptions are formulated on the basis of Differentiation of
Signs and Symptoms, and the subsequent application of therapeutic principles and the
right choice of drugs. Through an understanding of individual drug properties and
their logical combinations, the therapeutic potential of the drugs could be maximized,
with their toxic side effects being minimized or neutralized. The synergistic action
exhibited by multi-component prescriptions is therefore effective for the management
of more complicated diseases.
III. The monarch, minister, assistant and guide of herbal formulas

Formulating a prescription requires, but is not limited to, the understanding of the
disease progress and the principle of Treatment by Differentiation of Signs and Symptoms.
A prescription is not a random mix of individual herbs nor a casual addition of ther-
apeutic effect from individual component. The formulation is governed by a rationale
under which herbs are assigned as Monarch, Minister, Assistant or Guide, representing
their principal therapeutic roles and their inter-relationships. Based on the description
by various practitioners a summary of such classification is given as follows:
The Monarch refers to the component herb(s) in a prescription that possess(es) the prin-
cipal therapeutic action against the core disease or the major symptoms. It is the most
important herb in a prescription that possesses the most potent pharmacological action
and constitutes a greater proportion than that of the Minister or Assistant.
The Minister usually constitutes a lesser proportion and is less potent than the Monarch.
It may be refered to as the component that enhances the action of the Monarch in
treating severe diseases or symptoms. Or it may be referred to as the component that
is targeted at treating complications or minor symptoms associated with a disease.
The Assistant, in turn, is less potent and constitutes a lesser proportion than the Minister.
The Assistant may serve in three roles: (1) to enhance the actions of the Monarch and
Minister or to treat minor symptoms directly; (2) to relieve or counteract the toxicity
and side effects of the Monarch and Minister; (3) under some pathological conditions,
to produce a synergistic effect with the Monarch even though it may possess opposing
nature and taste as compared with the Monarch.
The Guide is a mild drug that is used in small amounts in a prescription. It may be
used for facilitating the delivery of the various components in the formula to target
organs, or to regulate the activities of other herbs.
When composing a prescription, the number of herbs assuming the role of Monarch
should best be limited to unity, or at most two under more complicated situations, since
more Monarchs would contribute to reduced efficacy due to dispersed pharmacological
actions and undesirable pharmacological interactions. On the other hand, the number
of Ministers could be larger than that of the Monarch, while the number of Assistants
could be larger still, but that for Guides should be one or two. After all, the composition
of a prescription should be formed with reference to the progress of the disease and the
choice of therapeutic principles, as well as the pharmacological properties of the herbs.
The concept of Monarch, Minister, Assistant and Guide is further exemplified by the
Herba Ephedrae Decoction, as illustrated below.
IV. Example of a TCM prescription

The Herba Ephedrae Decoction is indicated for the treatment of cold and flu caused by
exogenous evils. These evils arise from wind-cold, with symptoms like: intolerance to
cold weather, fever, headache, body pain, shortness of breath without sweating, thin
and white fur on the tongue, floating and tense pulse. The pathogenesis of the disease
involves the invasion of pathogens that block the superficies and trigger the body’s
immune response, as manifested by fever, intolerance to cold, headache and body pain.
According to the theory of TCM, the lungs control the vital energy (Qi) of the body and
are functionally coupled with the skin. Pathogenic changes such as blockade of the
skin and obstruction of the pulmonary-Qi therefore give rise to explain the symptoms
of the shortness of breath without sweating. Therefore, treatment should be aimed at
inducing perspiration (diaphoresis), relieving superficies, clearing pulmonary obstruction
and suppressing shortness of breath. The prescription includes Herba Ephedrae 9 g,
Ramulus Cinnamomi 6 g, Semen Armeniacae 6 g and Radix Glycyrrhizae 3 g. Components
of Herba Ephedrae Decoction are:
Herba Ephedrae – the Monarch: inducing perspiration and diaphoretic to disperse wind-
cold; releasing pulmonary-Qi to suppress shortness of breath.
Ramulus Cinnamomi – the Minister: inducing perspiration, relieving muscular stiffness,
warming meridians to activate Yang; capable of enhancing the diaphoretic action of
Herba Ephedrae, as well as regulating Ying-Qi and Wei-Qi, relieving pains in the body
and appendages.
Semen Armeniacae – the Assistant: releasing and suppressing pulmonary-Qi to assist
Herba Ephedrae in suppressing shortness of breath; dispersing wind and cold to enhance
the diaphoretic actions of Herba Ephedrae and Ramulus Cinnamomi.
Radix Glycyrrhizae – the Guide: regulating and neutralizing various herbs; to neutralize
the pungent and dry properties of Ramulus Cinnamomi and prevent excessive perspiration
induced by Herba Ephedrae.
It should be noted, however, that not every prescription carries Minister, Assistant
and Guide and a single herb may not have the same role in every prescription. If the
disease or condition is simple, treatment with a single or two herbs will suffice. If
neither the Monarch nor Minister is toxic or too potent, there is no need for an Assistant.
On the other hand, a Guide would not be needed should the main drugs be able to
reach the target organs by themselves. For example, Shengmai San, which is indicated
for the deficiency of Yin and Qi, comprises three herbs: Radix Ginseng serving as the
Monarch, Radix Ophiopogonis as the Minister and Fructus Schisandrae as the Assistant.
The application of the theory encompassing Monarch, Minister, Assistant and Guide
in prescriptions was a milestone in the development of disease treatment in TCM and
a culmination of a huge amount of clinical experience over time.
THE ORIGIN OF SHENGMAI SAN – THE RATIONALE OF

FORMULATION
Shengmai San (SMS) is a well-known TCM formula that has been thought to originate
from the Neiwaishang Bianhuolun (Differentiation on Endogenous and Exogenous Diseases)
(Li 1213), but was later validated to originate from Yixue Qiyuan (Origin of Medicine)
(Anonymous 1186). It is a formula that employs the therapeutic principles of invigor-
ating the Qi and promotes body fluid production, and is indicated for symptoms of heat-
induced depletion in primordial-Qi, Qi and body fluid, or deficiencies of the Yin and Qi.
It comprises the three herbs, namely, Radix Ginseng, Radix Ophiopogonis and Fructus
Schisandrae.
SMS is indicated for impairment in the regulation of the Qi and body fluid as mani-
fested by profuse sweating, lassitude, shortness of breath, reluctance of speech, dryness
of the larynx, thirst, asthenic and rapid pulse, as well as deficiency of the lung due to
prolonged coughing. It is also indicated for deficiencies of the Yin and Qi, as manifested
by dry cough with little phlegm, shortness of breath, spontaneous sweating, dryness of
the mouth and tongue, asthenic and small pulse.
According to the theory of TCM, sweat is part of the body fluid that originates from
the heart. Profuse sweating would thus impair the heart-Yin, as manifested by dryness
of the mouth and tongue, dysphoria, thirst, weak and asthenic pulse. On the other
hand, the lung controls the Qi. Spontaneous sweating would thereby consume the Qi
and cause impairment in the lung, as manifested by shortness of breath and lassitude.
Patients with impairment of the lung by prolonged coughing usually exhibit deficiencies
of both the Yin and Qi, and therefore can be treated by invigorating the Qi, nourishing
the Yin and promoting the production of the body fluid.
Radix Ginseng assumes the role of the Monarch in the SMS prescription. It is sweet
in taste and warm in nature, capable of supplementing the lung with its actions of
invigorating the Qi and promoting body fluid production. Radix Ophiopogonis assumes
the role of the Minister by nourishing the lung and promoting body fluid production. It
is sweet in taste and cold in nature, capable of nourishing Yin and clearing away heat. The
combined use of Radix Ginseng and Radix Ophiopogonis produces a synergistic effect of
invigorating the Qi and nourishing the Yin. Fructus Schisandrae, which is sour in taste
and warm in nature, assumes dual roles of the Assistant and Guide in SMS. It is capable
of astringing the lung, stopping excessive sweating and thirst, and promoting body
fluid production. When the supplementing, nourishing and astringing functions of the
three herbs are put together, they produce the effect of invigorating the Qi, nourishing
the Yin, promoting body fluid production, quenching thirst, astringing the Yin and
stopping excessive sweating. SMS, literally means ‘decoction for restoring pulse’, and
was coined by its main action of invigorating the Qi, which is vital for sustaining a
strong pulse. In addition, SMS may also be used to treat the deficiencies the Yin and
Qi associated with deficiency of the lung induced by prolonged coughing.
With hundreds of years of practical experience, the efficacy of SMS has been con-
firmed and widely adopted in clinical situations. It has attracted much attention from
the medical field and a large amount of research and clinical trials have been initiated
since the 1970s. Clinical application of SMS in the treatment of cardiovascular diseases
has been increasing, including the treatment of heart failure, ischemic cardiomyopathy
and shock.
CHEMICAL AND PHARMACOLOGICAL STUDIES ON THE

FORMULATING PRINCIPLES OF SMS
The China Academy of Traditional Chinese Medicine have compared the effects of
individual herbs and a standard preparation of SMS injection on the coronary flow and
myocardial contractility of rat hearts, using Langendorff perfusion technique. Using
pituitrin-(4 U/L)induced global ischemia in isolated perfused rat hearts, the effects
of herbal preparations from various combinations of component herbs of SMS (7 com-
binations in total) were examined. Zhu et al. (1998a) have investigated the dynamic
changes in chemical composition in SMS preparations and found that decoction of
Radix Ophiopogonis and Fructus Schisandrae mixture could generate the antioxidant,
5-hydroxymethyl-2-furaldehyde (5-HMF), the formation of which increased as the
amount of Radix Ophiopogonis was increased. In another study by the same authors
(Zhu et al. 1998b), it was found that the saponin contents in various combinations of
the component herbs varied, and the major saponin component in SMS were Rg2, Rg3,
Rh1 and Rgf. While the content of Rg3 and Rh1 were increased in SMS, the contents
of Rb, Rc, Rd and Re were decreased beyond detection. With regard to the Rg3 and
Rh1, the optimal ratio of Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae
should be 1:3:1.5.
I. Effects of SMS and its individual herbal component in

isolated normal rat heart
A. Effects on coronary flow (Figure 1.1)

At a concentration of 1.0 g/L, Radix Ginseng and Fructus Schisandrae extracts produced
a similar effect in terms of time course and extent in enhancing coronary flow, with
the effect peaking at 5–10 minutes after drug administration and then declined
gradually. While Radix Ophiopogonis extract alone did not produce any enhancing effect
on coronary flow, SMS produced a slow-onset, sustained and potent action that peaked
at 20 minutes. The effect of SMS observable at 30 minutes was larger than that of the
combination of the three individual herbs administered at the same time.
Figure 1.1 Effect of SMS and extracts of its component herbs on coronary flow of normal
rats. (All extracts were administered at 1.0 g/l) Herbal extracts: GS – Radix
Ginseng; MD – Radix Ophiopogonis; FS – Fructus Schisandrae; SMS – Shengmai
San; CON – Control.
*, ** p < 0.05 and p < 0.01, respectively, when compared with the control.
B. Effects on myocardial contractility (Figure 1.2)

SMS and the three component herbs showed a tendency to enhance myocardial con-
tractility at low concentrations and inhibit myocardial contraction at higher concentra-
tions ( p < 0.01), except for Fructus Schisandrae extract which showed a potent inotropic
effect ( p < 0.05) at all doses.
II. Study of the protective effects of SMS, its component herbs and
combinations against myocardial ischemia in isolated rat hearts
Dosage of extracts: Radix Ginseng 0.1 g/l, Radix Ophiopogonis 0.3 g/l, Fructus Schisandrae
0.15 g/l, SMS: sum of individual herbal component.
A. Effect on coronary flow (Figure 1.3)

The three extracts of individual component herbs enhanced the coronary flow in
ischemic rat hearts to varying extents. Radix Ginseng showed a slow onset of action,
with a gradual increase in activity over time that surpassed those of Radix Ophiopogonis
and Fructus Schisandrae beyond 15 min. Radix Ophiopogonis, on the other hand, pro-
duced a rapid onset but short duration of action, while Fructus Schisandrae exhibited
only a mild effect. SMS extract produced a similar action to Radix Ginseng but with
a higher potency; it could significantly reverse coronary spasm induced by pituitrin
and increased coronary flow by 71.8 per cent at 30 minutes after drug administration
( p < 0.01).
Figure 1.2 Effects of SMS and extracts of its component herbs on myocardial contractility
in isolated normal rat hearts (30 min after drug administration). Herbal extracts:
GS – Radix Ginseng; MD – Radix Ophiopogonis; FS – Fructus Schisandrae; SMS –
Shengmai San.
*, ** p < 0.05 and p < 0.01, respectively, when compared with the control.
Figure 1.3 Effects of SMS and extracts of its component herbs on coronary flow in isolated
rat heart under ischemic condition. Herbal extracts: GS – Radix Ginseng; MD –
Radix Ophiopogonis; FS – Fructus Schisandrae; SMS – Shengmai San; CON –
Control.
*, ** p < 0.05 and p < 0.01, respectively, when compared with the control, n = 7 for all groups.
Table 1.1 Effects of the three herbal components of SMS on coronary flow – ANOVA of a
23 factorial design
Source of error Degree of freedom Sum of square Mean square F-value P-value
Total 55 30726.9
Between group 7 25775.7
GS 1 17048.3 17048.3 165.3 <0.01
MD 1 3478.6 3478.8 33.7 <0.01
FS 1 2949.8 2949.8 28.6 <0.01
GS-FS 1 280.4 280.4 2.72 <0.05
GS-MD 1 283.1 283.1 2.74 <0.05
FS-MD 1 1082.1 1082.1 10.49 <0.01
GS-MD-FS 1 653.5 653.5 6.34 <0.05
Error 48 4951.2 103.2

F0.05 = 4.04 F0.01 = 7.20
Figure 1.4 Effects of SMS and various extracts of its component herbs on coronary flow of
isolated rat hearts under ischemic conditions (30 min after drug administration).
Herbal extracts: GS – Radix Ginseng; MD – Radix Ophiopogonis; FS – Fructus
Schisandrae; SMS – Shengmai San; CON – Control.
** p < 0.01 when compared with the control, with n = 7 for all groups.
The effect of various extracts on coronary flow at 30 minutes after drug adminis-
tration was analyzed by ANOVA (Table 1.1). Table 1.1 and Figure 1.4 shows that the
three herbs have significant contribution ( p < 0.01) to the pharmacological actions of
SMS. Among them, Radix Ginseng had the most contribution, with F-value being greater
than 165.3 and greater than those of other inter-group values, suggesting the leading
role of Ginseng in the formulation. Interaction among the 3 individual herbs was
Figure 1.5 Effects of SMS and various extracts of its component herbs on myocardial
contractility of isolated rat hearts under ischemic conditions (30 min after
drug administration). Herbal extracts: GS – Radix Ginseng; MD – Radix
Ophiopogonis; FS – Fructus Schisandrae; SMS – Shengmai San; CON – Control.
** p < 0.05 when compared with the control, with n = 7 for all groups.
obvious ( p < 0.05). The fact that the effect of SMS was stronger than that of the sum
of individual herbs suggests a synergistic effect produced by the multi-component
prescription.
B. Effect on myocardial contractility

The effects produced by SMS and the three individual herbs on myocardial contractility
were shown in Figure 1.5. At 30 minutes post-dosing, the action produced by SMS
was most potent ( p < 0.05).
In summary, the enhancing effect on coronary flow produced by SMS was stronger
than the sum of those of the three individual herbs. SMS exhibited a sustained inhibitory
action against coronary spasm induced by pituitrin. The significant interaction among
the three components suggests a synergistic action produced by SMS, which provides
a scientific basis for the multi-component formulation in TCM.
In TCM, the formulation of a prescription follows the rule of Monarch, Minister,
Assistant and Guide. Experimental studies have demonstrated that the lowering of
coronary resistance and enhancement of coronary flow by SMS is mainly afforded by
Radix Ginseng, a Monarch herb in the prescription. While the effects produced by
Radix Ophiopogonis (Minister) and Fructus Schisandrae (Minister) are not prominent,
they can enhance the action of Radix Ginseng. These observations are in line with
the theory in TCM that the Minister and Assistant serve to enhance the action of the
Monarch.
TRADITIONAL AND CONTEMPORARY CLINICAL
APPLICATIONS OF SMS
According to the Standard for Diagnosis and Treatment (Wang 1602), SMS, comprising
Radix Ginseng 25 g, Radix Ophiopogonis 15 g and Fructus Schisandrae 15 g, is decocted
with water and can be consumed all year round. Contemporary use of the prescription
include (1) decoction with water; and (2) injection (s.c. or i.v.), 2– 4 ml each time,
administered every 1–2 hours. SMS is prescribed for invigorating the Qi and promoting
body fluid production, astringing the Yin and stopping sweating. SMS is indicated for
the treatment of (1) deficiencies of the Yin and Qi, as manifested by lassitude, shortness
of breath, reluctance of speech, thirst, hidrosis, dryness of the throat and tongue, and
indistinct pulse; and (2) impairment of the lung due to persistent cough, impairment
of the Yin and Qi, dry cough with little phlegm, shortness of breath, spontaneous
sweating and asthenic pulse.
Apart from the treatment of diseases associated with deficiencies of the Yin and Qi,
such as heat stroke, infantile summer fever, functional hypothermia and other acute
feverish diseases, SMS has been frequently used in dealing with clinical conditions
of heart failure, shock and cardiomyopathy. In addition, SMS, with minor alterations
of the formula, may also be applied to tachycardia, angina, arrhythmia, neurasthenia,
Keshan Disease, bronchitis associated with Yin- and Qi-deficiencies, and persistent cough
associated with tuberculosis. If it is used for treating depletion of the Yin, the amount
of Radix Ginseng in the prescription should be increased accordingly. On the other
hand, as SMS possesses astringing action, it should not be used if the exogenous evils
(pathogens) or heat syndromes (fever) prevail without accompanying impairment of the
Qi and the body fluid.
SMS-RELATED FORMULATIONS AND THEIR CLINICAL

APPLICATION
I. Modified Shengmai powder

Reference: Analysis of Epidemic Febrile Diseases, Vol. 1 (Wu 1798)
Formulation: Radix Adenophorae Stritae, Radix Ophiopogonis, Fructus Schisandrae, Cortex
Mutan Radicis and Radix Remanniae.
Functions: Cooling the blood, nourishing the Yin, promoting body fluid production.
Indications: latent summer-heat, warm mouth, hidrosis and red tongue.
II. Shengmai drink

Reference: Chinese Pharmacopoeia Vol. 1 (Ministry of Health, China 2000)
Formulation: Radix Codonopsis Pilosulae, Radix Ophiopogonis and Fructus Schisandrae
Functions: Invigorating the Qi and restoring pulse, nourishing the Yin and promoting
the production of body fluid production.
Indications: Palpitation, shortness of breath, indistinct pulse, asthenic sweat.
III. Ophiopogonis drink for clearing lung heat (Mendong Qingfeiyin)
Reference: Differentiation on Endogenous and Exogenous Diseases (Li 1213)
Formulation: Radix Astragali, Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Ginseng,
Radix Ophiopogonis, Radix Angelicae Sinensis and Fructus Schisandrae.
Functions: Supplementing the Qi, benefiting the spleen, clearing the lung heat and
nourishing the Yin.
Indications: Qi-deficiency of the spleen and lung, dry heat due to Yin-depletion,
asthmatic cough, non-traumatic hemorrhage, haematemesis, lassitude, weak and rapid
pulse.
IV. Cold decoction of Radix Ophiopogonis (Maimendong Yinzi)

Reference: Secret Record of the Chamber of Orchids Vol. II (Li 1336)
Formulation: Radix Astragali, Radix Ophiopogonis, Radix Angelicae Sinensis, Radix
Remanniae Recens, Radix Ginseng and Fructus Schisandrae.
Functions: Invigorating the Qi and nourishing the blood.
Indications: Persistent hematemesis.
V. Ginseng-Schisandrae decoction
Reference: A Collection of Pediatrics Vol. III (Chen 1750)
Formulation: Radix Ginseng, rinsed Radix Paeoniae Alba, Poria, Fructus Schisandrae,
Radix Ophiopogonis from the Province of Zhang, Radix Glycyrrhizae Praeparata, Rhizoma
Zingiberis Recens and Fructus Ziziphi Jujubae.
Functions: Invigorating the Qi and strengthening the spleen.
Indications: Persistent cough, deficiency of the spleen, visceroptosis, pale complexion
and white lips.
VI. Ginseng-Astragali powder

Reference: Main Rules in Medical and Health Service Vol. V (Luo, Yuan Dynasty)
Formulation: Radix Ginseng, Radix Gentianae Macrophyllae, Poria, Rhizoma Anmarrhenae,
Cortex Mori Radicis, Radix Platycodi, Radix Asteris, Radix Bupleuri, Radix Astragali,
Cortex Lycii Radicis, Radix Remanniae Recens, Rhizoma Pinelliae, Radix Paeoniae Rubra,
Radix Asparagi, Carapax Trionycis and Radix Glycyrrhizae Preparata.
Functions: Invigorating the Qi and nourishing the Yin, suppressing cough and resolving
phlegm.
Indications: Yin and Qi-deficiency; emaciation; lassitude; feverish sensation in the
palms, soles and heart; hectic fever and spontaneous sweating; dryness of the mouth
and throat; cough with bloody phlegm; chest and hypochondrium discomfort; red
tongue with little fur; small and rapid pulse.
VII. Radix Astragali powder
Reference: Taiping Benevolent Prescriptions Vol. 70 (Wang et al. 992)
Formulation: Radix Astragali, Cortex Lycii Radicis, Red Poria, Radix Ophiopogonis, Radix
Paeoniae Rubra, dried Radix Remanniae Recens, Radix Ginseng, Radix Bupleuri, Radix
Scutellariae, Radix Angelicae Sinensis, Radix Glycyrrhizae.
Functions: Invigorating the Qi and nourishing the blood, nourishing the Yin and
antipyretic.
Indications: Fever associated with consumptive diseases; emaciation; persistent pain in
the limbs; lassitude; dryness of the mouth and tongue; anorexia; acratia; red tongue
and small pulse.
VIII. Ginseng-Astragali powder

Reference: An Encyclopedia of Useful Prescriptions for Women (Chen 1237)
Formulation: Radix Ginseng, Radix Astragali (fried), Radix Puerariae, Radix Gentianae
Macrophyllae, Red Poria, Radix Ophiopogonis, Rhizoma Anmarrhenae and Radix Glycyrrhizae.
Functions: Invigorating the Qi, dipersing the heat and promoting the production of
body fluid.
Indications: Restlessness and dryness of the mouth associated with fever.
IX. Decoction for flaccid limbs (Wuwei Tang)

Reference: A Summary on Medicine from Clinical Practice Vol. III (Cheng 1732)
Formulation: Radix Ginseng, Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae,
Radix Angelicae Sinensis, Semen Coicis, Radix Ophiopogonis, Cortex Phellodendri and Rhizoma
Anmarrhenae.
Functions: Supplementing the spleen and invigorating the Qi; nourishing the Yin and
dispersing the heat.
Indications: Flaccid syndromes manifested as flaccid limbs and during early stages of
diseases.
X. Decocted paste of Polygonati essence (Yuhua Jian)

Reference: Yi Chun Sheng Yi
Formulation: Rhizoma Polygonati Odorati, Fructus Schisandrae, Radix Ophiopogonis, Radix
Adenophorae Strictae, Radix Codonopsis Pilosulae, Poria, Rhizoma Dioscoreae, Radix Dipsaci,
Radix Achyranthis Bidentatae and Rhizoma Atractylodis Macrocephalae.
Functions: Supplementing the lung-Qi and nourishing the lung-Yin.
Indications: Yin- and Qi-deficiency of the lung, walking incompetence.
XI. Decoction of ten herbs for nourishing primordial Qi
(Shiquan Yuzhen Tang)
Reference: Records of Traditional Chinese and Western Medicine in Combination (Zhang
1918–1934)
Formulation: Wild Radix Codonopsis, Radix Astragali Recens, Rhizoma Dioscoreae Recens,
Rhizoma Anmarrhenae, Radix Scrophulariae, fresh Os Draconis, fresh Concha Ostreae, Radix
Salviae Miltiorrhizae, Rhizoma Sparganii and Rhizoma Zedoariae.
Functions: Invigorating the Qi and nourishing the Yin, resolving blood stasis and
astringing.
Indications: Exhaustion manifested as emaciation, squamous and dry skin, hiccough,
asthma, dreaminess, spontaneous sweating, seminal emission; rapid, stringy, small and
indistinct pulse.
XII. Ginseng injection

Reference: Jilin Province Pharmaceutical Standards, 1985
Formulation: Radix Ginseng and glucose.
Functions: Invigorating the Qi to arrest depletion, promoting the production of body
fluid and tranquilizing the mind.
Indications: Exhaustion, depletion, dizziness, palpitation and diabetes associated the
insufficiency of the primordial-Qi.
Clinical Applications: Treatment of shock, neurasthenia, diabetes, cancers and
hypotension.
XIII. Ginseng-Ophiopogonis injection

Reference: Valuable Prescriptions (Sun, mid-7th century), Chui Provincial Pharmaceuti-
cal Approval Number 001552 (1981)
Formulation: Radix Ginseng and Radix Ophiopogonis.
Functions: Invigorating the Qi and promoting the production of body fluid, suppressing
thirst and preventing exhaustion.
Indications: Deficiency of the Qi and depletion of body fluid induced by various diseases,
manifested as symptoms of syncope and deficiencies, such as dizziness, spontaneous
sweating, palpitation, thirst, indistinct pulse.
Clinical Applications: Shock, hypotension, arrhythmia, coronary heart disease, epidemic
hemorrhagic fever and myocarditis.
XIV. Astragali-Shengmai drink

Reference: Differentiation on Endogenous and Exogenous Diseases, Zhe Provincial Phar-
maceutical Approval Number 050701 (1996)
Formulation: Radix Astragali, Radix Codonopsis Pilosulae, Radix Ophiopogonis and Fructus
Schisandrae.
Functions: Invigorating the Qi and tonifying the Yin, nourishing the heart and supple-
menting the lung.
Indications: Deficiency of the Yin and Qi, palpitation and shortness of breath associated
with coronary heart disease and senility.
Clinical Applications: Coronary heart disease and debility associated with old age.
XV. Treasure for preserving youth (Qingchun Bao)

Reference: Zhejiang Province Pharmaceutical Standards (1985)
Formulation: Radix Ginseng, Radix Asparagi, Radix Rehmanniae, etc.
Functions: Invigorating the Qi and nourishing the blood, tonifying the Yin and promot-
ing the production of body fluid, tranquilizing the mind and anti-aging.
Indications: Deficiency of the Qi and hemophthisis, lassitude, asthma associated with
physical exercise, anorexia; palpitation, amnesia, insomnia; general debility due to
sickness or old age.
Clinical Applications: Middle-aged people who consume the prescription regularly
could see improvement in energy, mentality, endurance and adaptability to envir-
onment. It also supports the immune system and improves the body’s resistance to
diseases.
XVI. Hypoglycemic agent (Taizi Bao) (experimental formula)

Formulation: Fructus Schisandrae, Radix Berberidis, Cuculus Poliocephalus from Xingan,
Cortex Syringae, Radix Stemonae, Rhizoma Zingiberis and Radix Ginseng.
Functions: Tonifying and nourishing the five viscerae, promoting body fluid production
and quenching thirst, suppressing abnormalities in stomach and its regulation.
Indications: Diabetes.
XVII. Tonic for benefiting the heart (Zhenqi Fuzheng Tang)

(empirical formula)
Reference: Pharmaceutical Approval Number Z-64 (1992)
Formulation: Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae and Rhizoma
Anmarrhenae, etc.
Functions: Invigorating the heart-Qi, nourishing the heart-Yin and improving circulation.
Indications: Deficiency of the heart-Qi or deficiencies of the Yin and Qi; chest pain
associated with atherosclerosis.
Clinical Applications: Coronary heart disease and angina.
REFERENCES
Anonymous (1186) Origin of Medicine.

Anonymous (Warring States) Canon of Internal Medicine.
Chen, F.Z. (1750) A Collection of Pediatrics.
Chen, Z.M. (1237) An Encyclopedia of Useful Prescriptions for Women.
Cheng, G.P. (1732) A Summary on Medicine from Clinical Practice.
Li, G. (1213 or 1247) Differentiation on Endogenous and Exogenous Diseases.
Li, G. (~1336) Secret Record of the Chamber of Orchids.
Luo, T.Y. (Yuan Dynasty) Main Rules in Medical and Health Service.
Ministry of Health, China (2000) Chinese Pharmacopoeia.
Sun, S.M. (mid-7th century) Valuable Prescriptions.
Wang, H.Y. et al. (992) Taiping Benevolent Prescriptions.
Wang, K.T. (1602) Standard for Diagnosis and Treatment.
Wu, J.T. (1798) Analysis of Epidemic Febrile Diseases.
Zhang, X.C. (1918–1934) Records of Traditional Chinese and Western Medicine in Combination.
Zhu, D.N., Li, Z.M., Yan, Y.Q., and Zhu, J.G. (1998a) Studies on the relationship between
the dynamic changes in chemical composition and the pharmacological activities of Shengmai
San: chemistry of SMS II, China Journal of Chinese Materia Medica, 23, 291–3.
Zhu, D.N., Li, Z.M., Yan, Y.Q., and Zhu, J.G. (1998b) Studies on the relationship between
the dynamic changes in chemical composition and the pharmacological activities of Shengmai
San 6: changes in the composition of ginsenoside, Academic Periodic Abstracts of China, 4,
869–71.
16 Kam-Ming Ko et al.
2 Pharmacological studies on
Shengmai San
Kam-Ming Ko, Duncan H.F. Mak, Tze-Kin
Yim and Yong-Qing Yan
INTRODUCTION
Shengmai San (SMS) is a well-known traditional Chinese medicine formula, and has been
used in China for more than eight hundred years. SMS is comprised of Radix Ginseng
(Panax ginseng C.A. Meyer), Radix Ophiopogonis (Ophiopogon japonicus Ker-Gawl ) and Fructus
Schisandrae (Schisandra chinensis (Turcz.) Baill ) and is prescribed for replenishing the Qi
(vital energy) and promoting the production of body fluid, retaining the Yin and halting
the excessive perspiration. Traditionally, SMS is used for the treatment of body dis-
orders including: (1) heat-induced damage of the Qi and the deficiency of both the
Qi and the Yin caused by the depletion of the Yin-fluid, with symptoms of profuse
sweating, thirst, throat dryness, dyspnea, tiredness, weak pulse, red and dry tongue
without saliva, and (2) heart and lung weakness and the deficiency of the Qi and the
Yin due to protracted illness, with symptoms of cough with little phlegm, shortness of
breath with spontaneous perspiration, dry mouth and hot tongue, and weak and faint
pulse. Concomitant with a huge amount of clinical research having been done since the
1970s, SMS is commonly used in clinical practices with a prudent therapeutic efficacy,
and its area of clinical application is being rapidly extended. Nowadays, SMS is clinically
used for the treatment of shock caused by cardiovascular diseases, contractile heart
failure, and myocardial ischemia etc. With regard to pharmacological studies, a lot of
experimental work has also been done on SMS. In one of the large-scale cooperative
research projects, SMS (prepared by standardized manufacturing procedures) was used
for investigating the effect on cardiovascular system. Four main categories of experi-
mental models were adopted, including those for contractile heart failure, myocardial
ischemia, arrhythmia and shock. Experimental methods of different levels and standards
were used for investigations, in which various physiological and pharmacological markers
were measured. Other pharmacological studies on SMS have demonstrated the effect on
experimentally-induced atherosclerosis and blood lipid content, the stimulatory action
on immune system, the prevention against anaphylaxis, tissue injury and mutation
induced by toxins, and the effect on the central nervous system. Recently, antioxidant
activities of SMS have been investigated, which further provide a pharmacological
rationale for preventive and therapeutic effect of SMS on cardiovascular diseases as well
as for health safeguarding.
Pharmacological studies 17
CARDIOVASCULAR SYSTEM
I. Myocardial ischemia
A. Effect on pituitrin-induced changes in coronary flow in isolated rat hearts

Isolated rat heart was perfused with pituitrin-containing perfusate (40 u/L). After 2-
min of perfusion, the coronary flow was significantly reduced, with the lowest coronary
flow being achieved after 5 min of perfusion. The coronary flow was further reduced by
35 per cent after 30 min of perfusion. The supplementation of SMS in the perfusate
(0.5 g/ml) could significantly enhance the coronary flow by 71.8 per cent, indicating
the ability of SMS to antagonize the coronary spasm caused by pituitrin (Fig. 2.1)
(Wang and Li 1990).
B. Effect on isoproterenol-induced myocardial damage in rats

Rats were treated orally or injected intraperitoneally with SMS at a daily dose of 11/12
or 2.75/5.5 g/kg, respectively, consecutively for 8 or 10 days. One hour after the last
dose, the animals were injected intraperitoneally with urethane (0.4 g/kg) for basic
anesthesia, and then completely anesthetized with diethyl ether. ECG of channel II
and five parallel channels attached to the thoracic region were recorded for comparison.
Isoproterenol was given to animals by both intraperitoneal and subcutaneous injection
at a dose of 2 mg/kg. ECG was continuously recorded for 30 min after the injection.
After 24 hours the second injection of isoproterenol was given at the same dosage, and
the ECG prior to and after the drug injection was also recorded. The animals were then
sacrificed and blood samples were drawn for measuring plasma creatine phosphokinase
Figure 2.1 Effects of SMS on coronary flow in isolated rat heart under ischemic condition.
Herbal extracts: SMS – Shengmai San; CON – Control.
* p < 0.05, ** p < 0.01 when compared with the control, with n = 7 for all groups.
(CPK) activity. Injection of rats with isoproterenol could cause myocardial damage,
as indicated by the change in ST segment of the ECG and the elevated plasma CPK
activity. Oral pretreatment with SMS at the indicated dose could significantly lower
the elevation and reduce the total shift of the ST segment, while intraperitoneal injec-
tion of SMS could significantly reduce the total shift of the ST segment as well as the
plasma CPK activity (Zhang et al. 1990).
II. Contractile heart failure
A. Effect on pentobarbital-induced contractile heart failure in dogs

In a canine model of acute contractile heart failure (Li et al. 1990a), administration of
pentobarbital (30 mg/kg, iv) could significantly change most of the hemodynamic
parameters. While LVSP, LVdp/dtmax and MAP were reduced by 70, 80 and 70 per
cent, respectively, R-LVdp/dtmax was increased by 12 per cent. Heart rate and cardiac
output were reduced by 20 and 50 per cent, respectively. After the induction of acute
contractile heart failure, intravenous infusion of SMS (0.5–2.0 g/kg; 0.08 ml/min/kg)
for 60 min could increase LVSP, LVdp/dtmax, MAP, heart-rate and cardiac output,
but did not produce any effect on R-LVdp/dtmax. When compared with SMS, ouabain
(60 µg/kg) showed a more apparent and efficacious positive inotropic effect. Recent
research indicated that the action mechanism of SMS in producing the myocardial
effect involved a multiplicity of events. These include the suppression of cardiomyocyte
membrane Na+/K+-ATPase activity (Beijing College of Traditional Chinese Medicine
1973), the enhancement on cellular anabolism for protection against ischemic and
anoxic myocardial damage and the elevation of tissue glycogen and ATP content, the
enhancement on DNA and RNA synthesis, and the maintenance of cellular membrane
integrity under conditions of toxin-induced myocardial damage (Liu et al. 1978). The
ability of SMS to produce beneficial modulatory effect on myocardial metabolism under
the condition of myocardial injury was superior to the action produced by ouabain
(Li et al. 1990a).
B. Effect on pentobarbital-induced contractile failure in isolated rat hearts

Isolated heart was given perfusate supplemented with pentobarbital at a concentration
of 0.5 g/L to induce failure and cardiac arrest. When being perfused back with physio-
logical perfusate, the heart could restore beating. SMS, when given at doses ranging
from 0.5–1.0 g/L, could delay the onset of cardiac arrest and hasten the resumption
of beating following cardiac arrest, while ouabain (0.1–1.0 µmol/L) could not produce
any effects. When given at same dosage again, SMS could significantly prolong the
duration of heart beating and significantly shorten the time elapsed between cardiac
arrest and resumption of heart beating (Li et al. 1990c).
C. Effect on pentobarbital-induced acute contractile failure in

cultured rat cardiomyocytes in vitro
The myocardial effect of SMS was examined using a cellular model of pentobarbital-
induced acute contractile failure. Ouabain (0.17 µmol/L) could significantly counteract
the pentobarbital-induced contractile failure in cultured cardiomyocytes, but the
protection was associated with arrhythmic contraction. SMS, when added at a final
concentration of 1 mg/ml, could restore the contractile function of cardiomyocytes,
with a normal frequency and rhythm of beating. Both ouabain and SMS treatment
could significantly delay the onset of cardiac arrest induced by pentobarbital (Li et al.
1990b).
III. Cardiac arrhythmia
A. Effect on cardiac arrhythmia induced by electrical stimulation on

rabbit hypothalamus
Electrical stimulation on rabbit hypothalamus caused frequent supraventricular and
ventricular arrhythmic response. Oral treatment of SMS at a dose of 4.4 g/kg could
significantly prevent the cardiac arrhythmia caused by electrical stimulation on the
hypothalamus (Hou et al. 1990).
B. Effect on ventricular fibrillation induced by chloroform in mice

After being anesthetized with chloroform, the rate of endoventricular fibrillation in mice
was observed for 30s. Intraperitoneal injection of SMS at doses ranging from 8.25–
13.75 g/kg could significantly protect against the ventricular fibrillation induced by
chloroform (Hou et al. 1990).
C. Effect on cardiac arrhythmia induced by calcium chloride in rats

Rapid intravenous perfusion of 10 per cent calcium chloride solution at a dose of
0.15 g/kg caused lethal ventricular fibrillation in rats. When given SMS by intra-
peritoneal injection at a dose of 2.75 g/kg, the rats were protected against the lethal
effect of calcium chloride, as indicated by the reduction of mortality rate from 100 to
20 per cent (Hou et al. 1990).
D. Effect on cardiac arrhythmia induced by electrical stimulus to isolated

guinea-pig hearts
Electrical stimulation (16HZ; 7–14V) could induce ventricular fibrillation in isolated
and perfused guinea-pig hearts. Perfusate supplemented with SMS (0.11 g/min) could
produce an anti-fibrillation rate of 66.7 per cent (Hou et al. 1990).
IV. Shock
A. Hemorrhagic shock
(1) Effect on hemorrhagic shock in rabbits

A rabbit model of hemorrhagic shock was established by blood letting till the blood
pressure was dropped to a level under 5.3 kPa (40 mmHg) and the lowered blood
pressure could sustain under 8 kPa (60 mmHg) for at least 20 min. Within 1 to 5 min
after the intravenous perfusion with SMS at a dose of 2.2 g/kg, the blood pressure
started to elevate. The duration of elevated blood pressure was maintained for 93.0 ±
16.4 min. When compared with the control, SMS could significantly protect against
the hemorrhagic shock, with the period of stable blood pressure being longer than that
of dextran (Chu et al. 1990).
(2) Effect on hemorrhagic shock in dogs

Intravenous injection with SMS at a dose of 2.2 g/kg could produce a significant
elevation in blood pressure at the early stage of acute hemorrhagic shock in the canine
model (Chu et al. 1990).
(3) Effect on ischemia-induced acute cardiac arrest in rats

The time taken to reach the onset of ischemia-induced cardiac arrest was observed in
blood-letting rats. SMS, given at a dose of 5.5 g/kg by either intraperitoneal or oral
administration could significantly delay the onset of cardiac arrest in ischemic hearts,
indicating the ability of SMS to protect against the hemorrhagic shock.
B. Endotoxin shock
(1) Effect on endotoxin-induced shock in rabbits

After the intravenous injection with purified E coli-derived endotoxin at a dose
equivalent to 1.5 times of LD50, the rabbit model of endotoxin shock was successfully
established when the blood pressure was dropped to less than one-third of the normal
level within 90 min. When given at a dose of 2.2 g/kg by intravenous injection, SMS
could produce significant protective effect on the endotoxin-induced shock, but failed
to reduce the mortality rate (Chu et al. 1990).
(2) Effect on endotoxin-induced shock in mice

Mice were pretreated orally with SMS at a daily dose of 5.5 g/kg for 3 days. One hour
after the last dose, the animals were given E. coli-derived endotoxin by intravenous
injection at a dose equivalent to 50 per cent of LD50. The same dosage of endotoxin was
given again 6 hr later. The mortality rate of animals in 24 hr was observed. Results
from this study indicated that SMS could significantly reduce the mortality rate caused
by the endotoxin shock in mice (Chu et al. 1990).
C. Cardiogenic shock
(1) Effect on acute heart dysfunction in rabbits

An animal model of acute heart dysfunction was established by intravenous injection
of olive oil into rabbits (Zhao et al. 1974). SMS was given by intravenous injection at
a dose of 2.2 g/kg 30 min prior to the injection of olive oil. Results from this study
indicated that SMS could significantly protect against the acute heart dysfunction
induced by olive oil-mediated lung occlusion, which was suggestive of preventive action
in cardiogenic shock (Chu et al. 1990).
(2) Effect on experimentally-induced cardiogenic shock in dogs

An open-chested canine model of cardiogenic shock was prepared by the ligation of
the anterior descending branch of coronary artery (Beijing Medical University 1974,
1975). The animal model was successfully established when the blood pressure was
decreased to a level below 9.33 kPa (70 mmHg) after the coronary ligation, with this
condition being sustained for 15 min. Intravenous dripping for 1 hr or intragastric
administration of SMS at a dose of 5.5 g/kg caused the recovery of the blood pressure
to a level exceeding that at the early phase of the shock, which was sustained above
9.33 kPa (70 mmHg) for 1 or 1.5 hr, respectively, following the drug administration.
This result indicated the significant therapeutic effect produced by SMS on cardiogenic
shock (Chu et al. 1990).
V. Atherosclerosis
Recently, it has been reported that inhibitors of blood platelet aggregation could inhibit
the formation of experimentally-induced atherosclerotic plaque (Smith and Hilker 1990).
Given the ability of SMS to suppress the aggregation and release of blood platelets, the
effect of SMS on atherosclerosis is described below.
A. Effect on experimentally-induced atherosclerosis

A rabbit model of atherosclerosis was prepared by feeding the animals daily with diet
supplemented with 1 g of cholesterol, consecutively for 6 weeks. Results obtained from
atherosclerotic (As) group, SMS-treated-As group and paeonol-treated-As group (positive
control) were compared with the control group (i.e. no cholesterol supplementation).
In the drug treatment group, animals were given SMS intragastrically or paeonol
intraperitoneally at a daily dose of 2.5 g/kg or 100 mg/kg respectively, for 6 days per
week and consecutively for 6 weeks. Microscopic examination on pathological changes
and the area of damage in aortic intima as well as histochemical analysis on pathological
tissues. This indicated that both SMS and paeonol treatment could ameliorate the
severity of pathological changes in the aorta, with reduced extents of intimal prolifera-
tion, lipid disposition, as well as lower lipase activity and extent of mucopolysaccharide
formation, when compared with the control group. These observations suggested that
SMS could significantly inhibit the formation of As plaques in aortic intima. Some
aortic smooth muscle cells in As animals was found with their nuclei perpendicular to
the intima, and the smooth muscle cells of the middle layer were found to invade the
endothelial layer at injured site of the elastic membrane. In contrast, the nuclei of
smooth muscle cells in SMS-treated animals were parallel with the elastic membrane.
These observations suggested that SMS could inhibit the movement of arterial smooth
muscle cells from the middle layer to the endothelial layer, which may be related
to the inhibitory action on As plaque formation. The ensemble of results indicated
that SMS could suppress the As-induced pathological changes in the aorta, including
intimal proliferation, connective tissue formation and lipid deposition, to varying extents
(Shi et al. 1990).
Table 2.1 Effect of SMS on serum lipids and lipoprotein cholesterol levels
Blood lipid content (mg/100ml, mean ± S.D.) HDLc/TCh AsI
TCh TG LDLc HDLc HDL2c HDL3c (ratio)
CON 757.9 105.0 702.6 2.74 11.0 16.4 0.036 0.964

±29.9 ±45.8 ±34.5 ±7.0 ±1.3 ±6.3 ±0.009 ±0.009
SMS 557.7** 85.4** 500.8** 39.8** 16.7** 23.1** 0.073** 0.925**
±137.6 ±42.0 ±127.3 ±6.3 ±4.3 ±3.2 ±0.013 ±0.010
Paeonol 749.2 161.2 683.2 29.8 10.5 19.3 0.040 0.960
±35.2 ±67.5 ±21.0 ±6.0 ±4.0 ±4.9 ±0.010 ±0.007
** p < 0.01 when compared with the control (CON)
B. Effect on the levels of serum lipids and cholesterol in lipoproteins in a

rabbit model of atherosclerosis
(1) Levels of serum lipids and cholesterol in lipoproteins

A rabbit As model was prepared by feeding cholesterol in the diet for 6 weeks. Venous
blood samples was taken from the ear ring region prior to the beginning of the first
week, on the fourth week and sixth week of cholesterol feeding. Blood samples were
measured for serum levels of total cholesterol (TCh), triglycerides (TG), low-density
lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDL C ) and its sub-
group cholesterol (HDL2C, HDL3C ). On the fourth and sixth week after the cholesterol
feeding, serum TCh and LDLC levels were significantly elevated, while HDLC and HDL2C
levels were significantly lowered when compared with the respective level prior to
cholesterol feeding. All these indicated the successful induction of hyperlipidemic status.
SMS treatment at a daily intragastric dose of 2.5 g/kg for 6 days per week, consecut-
ively for 6 weeks, could significantly lower serum TCh, and TG, as well as LDLC levels,
but increase the HDLC and HDL2C levels, when compared with the As control group.
Paeonol, when given by intraperitoneal injection at a daily dose of 100 mg/kg for
6 weeks, did not produce any detectable change in the levels of serum lipids and
lipoprotein cholesterol (Table 2.1) (Shi et al. 1990).
(2) As inducing index (AsI) and Anti-As index (HDLc /TCh)

It is widely accepted that both HDLc and HDL2c levels are the anti-As factors while
LDLc is regarded as As inducing factor. However, recent studies have demonstrated
that the As inducing index (AsI, TCh-HDLC )/HDL C ) and Anti-As index (HDLc /TCh)
would be a more sensitive parameter for the evaluation or forecast of incidence of As-
related cardiovascular diseases. Effect of SMS on these parameters in the As rabbit model
was examined. The results indicated that SMS treatment (2.5 g/kg, 6 days/week,
6 weeks) could significantly lower the AsI and elevate the Anti-As index (Table 2.1)
in the As rabbit model, when compared with the control.
According to the present experimental results, the mechanism involved in the sup-
pression of As plaque formation by SMS may be related to the following actions: (i)
inhibition of blood platelet aggregation which, in turn, suppresses the release of active
substances like platelet-derived growth factor, (ii) the modulation on the metabolism
of blood lipids, (iii) the suppression of As-inducing factor like LDLC level and (iv) the
enhancement of anti-As factors like HDLc and HDL2c levels (Shi et al. 1990).
VI. Toxin-induced myocardial injury
A. Effect on mitomycin (MMC)-induced myocardial ultrastructural

changes in mice
From three days onwards after the intraperitoneal injection with MMC at a dose of
5 mg/kg, the mice showed an abrupt decrease in body weight, reduction in physical
activities, messy body hairs, decrease in food intake and deep yellowish turbid urine.
SMS treatment at a daily dose of 10 g/kg for 3 days could slightly ameliorate the
progressive decrease in body weight of MMC-treated animals. Within 10-day period
of observation, the mortality rate in MMC-treated animals was 20 per cent, while all
SMS-treated animals survived after the MMC challenge. Electron microscopic examina-
tion showed that SMS could significantly protect against the MMC-induced damage
on the nucleus and myofibril of cardiomyocytes. In addition, SMS treatment also
produced a certain degree of protection to mitochondria and other cellular organelles
(Sun et al. 1990).
B. Effect on MMC-induced morphological and functional changes in

cultured rat cardiomyocytes
MMC did not produce any immediate effect on the beating performance of cardio-
myocytes, however, the degree of influence was increased with time. Six hours after the
addition of MMC at a final concentration of 1 mg/ml, the beating performance of
cardiomyocytes was attenuated, with the reduced amplitude of contraction being associ-
ated with a lowered frequency, but normal rhythm of beating. Twenty-four hours after
the administration of MMC, the beating performance was further attenuated, with a
further decrease in beating frequency associated with abnormal rhythm. A small number
of cardiomyocytes stopped beating, with morphological changes such as the decrease
in pseudocytoplasmic extensions that had wrinkled and shrunk into a circular shape.
Forty-eight hours after the MMC administration, most of the cardiomyocytes had
stopped beating or even detached and died. While SMS treatment did not produce any
detectable effect on the contractile function of normal cardiomyocytes, it significantly
protected against the MMC-induced deterioration on beating performance. When
added at a final concentration of 125 mg/ml, SMS increased the beating frequency by
42.2 per cent, when compared with the MMC-challenged control (Sun et al. 1990).
C. Effect on MMC-induced lactate dehydrogenase (LDH) leakage

from cultured cardiomyocytes in vitro
LDH is an intracellular enzyme present abundantly in myocardial cells. Under normal
conditions, cultured cardiomyocytes only release trace amounts of LDH into the culture
medium. However, when the cells are injured, the increase in membrane permeability
will cause a significant LDH leakage (Higgins et al. 1980). Experimental results demon-
strated that the extent of LDH leakage, indicative of cellular damage, was exaggerated
Table 2.2 Protective effect of SMS on MMC-induced myocardial injury
Dosage (µg/ml) Number of samples LDH (U, mean ± S.E.)
Control 6 32.8 ± 6.9
MMC 5 6 57.5 ± 3.2
MMC + SMS 250 6 65.0 ± 8.3
MMC + SMS 500 6 58.5 ± 4.9
MMC + SMS 100 6 38.1 ± 7.8*
* p < 0.05 when compared with the MMC group
Table 2.3 Effects of SMS on MMC-induced inhibition of DNA synthesis in cardiomyocytes

Dosage (mg/ml) No. of cell bottle CPM (mean ± S.E.) DNA synthesis (% change)
Control 7 2588.1 ± 94.4
MMC (1) 7 1290.6 ± 67.6 50.5
MMC + SMS (1) 7 1218.0 ± 130.7 47.6
MMC + SMS (125) 7 1443.3 ± 127.8 56.4
MMC + SMS (250) 7 1562.6 ± 92.0* 61.8
* p < 0.05 when compared with the MMC group
by increasing doses of MMC. SMS, when given at a concentration of 1 mg/ml, could

significantly reduce the LDH leakage from MMC-challenged (5 mg/ml) cardiomyocytes,
whereas lower doses (250 or 500 mg/ml) of SMS did not produce any significant effect
(Table 2.2) (Sun et al. 1990).
D. Effect on MMC-induced changes in DNA synthesis cultured rat

cardiomyocytes in vitro
Cardiomyocytes were isolated from neonatal rats for culture. On the third or fourth day
of culture, active cellular division and rapid DNA synthesis accompanied by maximum
3
H-TdR cellular uptake were observed (Blodel et al. 1971). Experimental results demon-
strated that the administration of MMC could decrease the 3H-TdR cellular uptake
in a dose-dependent manner, with more than 90 per cent of inhibition at doses greater
than 1 mg/ml. While SMS treatment only slightly enhanced the DNA synthesis in
the purified cardiomyocytes culture, it could produce significant protective effect on
MMC-induced inhibition on DNA synthesis. When added at final concentrations of
125 and 250 mg/ml, SMS could significantly increase the cellular uptake of 3H-TdR,
with the effect being more apparent at the high dose, when compared with the MCC-
challenged control (Table 2.3) (Sun et al. 1990).
E. Effect on adriamycin (ADR)-induced myocardial ultrastructural

changes in rats
Rats were administered intragastrically with ADR at a weekly dose of 2 mg/kg, con-
secutively for 10 weeks, pathological ultrastructural changes were found in myocardial
cells isolated from the animals. SMS treatment at an oral dose of 3 g/day for 10 weeks
could prevent the ADR-induced pathological ultrastructural changes in the rat heart
(Rong et al. 1983).
F. Effect on ADR-induced changes in cell division and

protein synthesis in cultured cardiomyocytes in vitro
Experimental results indicated that SMS, when added at a final concentration of
1 mg/ml, increased the cell division index of cardiomyocytes after the ADR-challenge.
SMS also enhanced the rate of protein synthesis in ADR-treated cardiomyocytes
(Zhang 1996).
G. Effect on ADR-induced Ca2++ overload in cultured cardiomyocytes

in vitro
Using fluorescent method for the detection of intracellular Ca2+ level, it was found
that ADR could obviously increase the intracellular Ca2+ level in cardiomyocytes. SMS
treatment could effectively suppress the ADR-induced overloading of intracellular Ca2+
(Zhang 1996). Experimental results also indicated that SMS treatment could inhibit the
alterations in sacroplasmic reticulum-mediated absorption and release of Ca2+ caused
by ADR (Zhang 1996).
VII. Viral myocarditis

Coxsackievirus B3 was used to reproduce a Balb/c mouse model of viral myocarditis.
The intraperitoneal injection of the virus to the animals was accompanied by a simult-
aneous administration of SMS at a daily dose of 11 g/kg, consecutively for 10 days.
SMS treatment significantly increased the survival rate of the viral intoxicated mice,
with a decrease in serum LDH activity, but no detectable changes in serum CPK and
aspartate aminotransferase (AST) activities. SMS treatment also produced a slight but
not significant protective effect on the pathological changes (i.e. necrosis, calcification
and infiltration) in myocardial tissue obtained from the infected animals (Table 2.4)
(Zhuang et al. in press).
Table 2.4 Effects of SMS on serum enzyme activities and survival rate in CVB3-infected mice at
day 10 of injection
CPK (U/L) LDH (U/L) AST (U/L) Survival
rate (%)
Non-infected control 315.6 ± 112.2 2334.4 ± 355.4 42.9 ± 15.8 100
CVB3 control 555.4 ± 192.4 3376.4 ± 457.5‡ 154.6 ± 31.0‡ 64†
CVB3-SMS (11 g/kg) 504.4 ± 184.3 2857.8 ± 494.4* 233.6 ± 81.4 100*
Each value is the mean ± S.D. with n = 7–10
* p < 0.05 when compared with the CVB3 control
†, ‡ p < 0.05 and p < 0.01 respectively, when compared with the non-infected control
Table 2.5 Inhibitory effects of SMS on voluntary mobility of mice
Dosage Number of experimental Mobility number Inhibitory rate
group (number of mice) (mean ± S.D.) (%)
Control 20 ml/kg 14 (28) 945.3 ± 181.0
SMS 5.5 g/kg 14 (28) 885.7 ± 178.2 6.3
11.0 g/kg 14 (28) 698.8 ± 130.6* 26.1
22.0 g/kg 14 (28) 598.8 ± 133.3* 36.6
Chlorpromazine 2.5 mg/kg 14 (28) 565.8 ± 162.3* 40.1
* p < 0.01 when compared with the control
CENTRAL NERVOUS SYSTEM (CNS)
I. Mice behavior activities
A. Effect on voluntary mobility in mice

Using a three-light path mice activities detecting machine (Yuan et al. 1985), the activ-
ity index of mice in various groups was simultaneously detected, and each experiment
was repeated 14 times. Experimental results indicated that intragastric administration
of SMS at a dose of 11 or 22 g/kg could inhibit the voluntary mobility by 26.1 or 36.6
per cent, respectively. Under the same experimental conditions, chlorpromazine
(2.5 mg/kg, ig) inhibited the voluntary mobility by 40 per cent. These indicated that
SMS could produce an inhibitory effect on the voluntary mobility in mice (Table 2.5)
(Yuan and Zhang 1990).
B. Effect on passive activities in mice

The experiment was performed using a bar rotation method. Mice were trained to
run on a rotary bar rotating at fifteen revolutions per min. Mice capable of running on
the rotary bar for more than 10 min without falling down were chosen for the experi-
ment. Fifty minutes after the intragastric administration of SMS at doses ranging from
11–33 g/kg, the number of mice falling down was recorded. Results from this study
indicated that SMS treatment did not produce a significant effect on muscle strength
or motor coordination. The ability of SMS to inhibit voluntary mobility, as mentioned
in previous section, was unlikely due to its effect on affecting the motor ability of the
animals. Similarly, chlorpromazine (4 mg/kg, ig) did not produce any detectable effect
on passive activities in mice (Yuan and Zhang 1990).
C. Effect on fighting and aggressive behaviors in mice

Male mice were maintained alone in a pottery can for more than one week. Animals
showing fighting and aggressive behaviors were chosen for the experiment. Experimental
results indicated that intragastric administration of SMS at a dose of 2.75 g/kg could
produce a suppressive effect on the fighting and aggressive behaviors in mice, but the
degree of suppression was smaller than that produced by chlorpromazine (5.0 mg/kg)
(Table 2.6).
Table 2.6 Inhibitory effects of SMS on aggressive behavior in mice
Dosage No. of mice Disappearance of aggressive
behavior (No.)
Control 25 ml/kg 10 0
SMS 13.75 g/kg 10 1
27.5 g/kg 10 6*
Chlorpromazine 5.0 mg/kg 10 10**
*, ** p < 0.05 and p < 0.01 respectively, when compared with the control
Table 2.7 Synergistic effect of SMS on the sedative-hypnotic action of pentobarbital

Dosage Number of animals Number of rats hypnotized
SMS 11 g/kg 28 6
22 g/kg 28 17*
Chlorpromazine 2.5 mg/kg 28 15*
II. Interactions with inhibitors and stimulants on CNS
A. Effect on the hypnotic action of pentobarbital in mice

One hour after the intragastrical administration of SMS or other drugs, mice were
injected intraperitoneally with pentobarbital at a hypnotic dose of 23 mg/kg. The
experimentors recorded the number of mice in different drug-pretreated groups that
became sleepy within 15 min, as indicated by the disappearance of the righting reflex
for more than 1 min. Experimental results from this study indicated that intragastric
administration of SMS at a dose of 22 or 33 g/kg or of chlorpromazine at a dose
of 2.5 mg/kg could produce a synergistic action with pentobarbital in hypnosis
(Table 2.7) (Yuan and Zhang 1990).
B. Effect on the stimulant action of chloral hydrate

One hour after the intragastric administration of SMS or other drugs, animals were
given choral hydrate by intraperitoneal injection (190 mg/kg), and the number of
mice in different groups becoming sleepy was recorded. The results indicated that
when given intragastrically, both SMS (22 or 33 g/kg) and chlorpromazine (4 mg/kg)
could produce a synergistic action with chloral hydrate in hypnosis (Table 2.8) (Yuan
and Zhang 1990).
C. Effect on the stimulant action of deoxy-ephedrine in mice

Mice given SMS or other drugs intragastrically were immediately injected intraperitone-
ally with deoxy-ephedrine (2 mg/kg). Forty-five minutes after the injection, activity
indices of animals in different groups were detected simultaneously for 10 min by using
Table 2.8 Synergistic effect of SMS on the action of chloral hydrate
Dosage Number of animals Number of rats hypnotized
SMS 11 g/kg 13 1
22 g/kg 13 7*
33 g/kg 13 8*
Chlorpromazine 4 mg/kg 13 11**
*, ** p < 0.05 and p < 0.01 respectively, when compared with the control
Table 2.9 Antagonistic effect of SMS on the action of deoxy-ephedrine

Number of experimental Mobility of mice
groups (number of animals) (mean ± S.D.)
Control Solution 25 ml/kg
+ Saline 10 ml/kg 8 (16) 861.6 ± 103.5
+ Metamfetamine 2 ml/kg 8 (16) 1512.5 ± 189.5*
SMS 16.5 g/kg
+ Metamfetamine 2 ml/kg 8 (16) 1357.0 ± 287.6
SMS 27.5 g/kg
+ Metamfetamine 2 ml/kg 8 (16) 1092.5 ± 114.7†
Chlorpromazine 5 mg/kg
+ Metamfetamine 2 ml/kg 8 (16) 787.8 ± 114.7†
† p < 0.01 when compared with the analeptic control
the photo-electrical method. Each experiment was consecutively repeated eight times.
Results from this study indicated that intragastric administration of SMS at a single
dose of 27.5 g/kg could antagonize the deoxy-ephedrine-induced stimulatory action in
mice (Table 2.9) (Yuan and Zhang 1990).
D. Effect on the stimulant action of amphetamine in mice

Mice treated intragastrically with SMS or other drugs were immediately injected intra-
peritoneally with amphetamine (4 mg/kg). One hour after the injection, the activity
index of animals was detected for 10 min. Each experiment was repeated consecutively
twelve–fourteen times. The results indicated that intragastric administration of SMS
at a single dose of 22 g/kg could antagonize the amphetamine-induced stimulatory
action in mice (Table 2.10) (Yuan and Zhang 1990).
III. Interaction with chemical inducers of convulsion in mice

Forty-five minutes after the intragastric treatment with SMS or other drugs, mice
were injected intraperitoneally with pentetrazole or strychnine at a dose of 60 or
1.2 mg/kg, respectively. The number of animals showing convulsion was recorded.
Table 2.10 Antagonistic effect of SMS on the action of amphetamine
Number of experimental Mobility of mice
groups (number of animals) (mean ± S.D.)
+ Saline 10 ml/kg 12 (24) 895.4 ± 135.7
+ Amphetamine 4 mg/kg 12 (24) 1258.0 ± 221.3*
SMS 11 g/kg
+ Amphetamine 4 mg/kg 14 (28) 1115.1 ± 145.9
SMS 22 g/kg
+ Amphetamine 4 mg/kg 14 (28) 1014.8 ± 115.1†
† p < 0.05 when compared with the analeptic control
The results indicated that SMS treatment (33 g/kg) could not prevent the incidence
of clonic and tonic convulsion caused by pentetrazole and strychnine, respectively
(Yuan and Zhang 1990).
IV. Body twisting response induced by acetic acid in mice

Forty-five minutes after the intragastric administration of SMS at a single dose of 11 or
22 g/kg, mice were intraperitoneal injected with 0.7 per cent acetic acid (10 ml/kg).
The number of body twisting responses of the animals was recorded. The results indic-
ated that SMS could not produce any analgesic action against acetic acid (Yuan and
Zhang 1990).
In summary, SMS could significantly reduce the index of voluntary mobility in
mice and suppress the fighting and aggressive behaviors of mice living in isolation.
SMS could also work synergistically with both barbital (pentobarbital) and non-barbital
(chloral hydrate) hypnotic drugs on the CNS. The ensemble of results demonstrated
the sedative effect of SMS.
V. Monoamine neurotransmitters
A. Dopaminergic system
(1) Time dependent changes in the levels of dopamine (DA) and its metabolites
(DOPAC and HVA) in rat corpus striatum
After treating rats orally with SMS at a dose of 11 g/kg, the level of DA in the corpus
striatum was elevated, with the maximum level being obtained at 4 hr after the
SMS treatment. Then the DA level declined gradually and returned to normal level at
8 hr after the treatment. Meanwhile, DOPAC and HVA (DA metabolites) levels were
increased to a maximum in the corpus striatum at 4 hr after the SMS treatment, with
DOPAC and HVA levels being increased by about 20 and 40 per cent, respectively.
Both DOPAC and HVA levels started to decline thereafter, but they did not return to
normal values at 8 hr after the treatment (Table 2.11) (Liu et al. 1990).
Table 2.11 Effects of SMS on the levels of dopamine (DA) and its metabolites in the corpus
striatum of rats
Time (hr) Corpus striatum (nµg/g)

DA DOPAC HVA
SMS (11 g/kg,ig) 0 7996.0 ± 264.4 676.9 ± 34.6 642.6 ± 38.5
1 8130.7 ± 332.1 770.4 ± 18.4 639.5 ± 52.4
2 7655.7 ± 210.7 898.1 ± 39.6* 755.4 ± 54.9
0 8140.6 ± 179.6 652.8 ± 39.2 623.0 ± 33.4
4 9011.4 ± 301.7* 809.2 ± 13.1† 914.9 ± 62.1**
8 8431.1 ± 335.1 738.8 ± 39.4 815.4 ± 61.8*
Each value is mean ± S.E. (n = 6)
* p < 0.05 when compared with t = 0
** p < 0.01 when compared with t = 0
Table 2.12 Effects of SMS on the levels of dopamine (DA) and its metabolites in the marginal
zone of rats
Time (hr) Peripheral zone (nµg/g)
DA DOPAC HVA
SMS (11 g/kg,ig) 0 1231.8 ± 97.1 404.7 ± 31.5 179.8 ± 23.9

1 1235.8 ± 88.8 402.6 ± 31.4 170.1 ± 14.3
2 951.3 ± 19.2* 478.5 ± 62.0 198.3 ± 23.4
0 1421.1 ± 72.7 420.4 ± 20.5 195.2 ± 6.1
4 1343.6 ± 80.0 522.6 ± 33.0* 229.0 ± 14.4*
8 1352.8 ± 99.4 523.4 ± 44.1* 252.9 ± 10.8**
(2) Time dependent changes in the levels of DA and its metabolites

(DOPAC and HVA) in the peripheral zone of rat proencephalon
In contrast to that in the corpus striatum, the DA level in the peripheral zone of pro-
encephalon was reduced by 20 per cent and then returned to the normal value at 2 and
4 hr respectively, after the oral SMS treatment (11 g/kg). DOPAC and HVA levels
were significantly elevated at 4 hr after the treatment, and they showed a continual
increase 8 hr thereafter (Table 2.12) (Liu et al. 1990).
B. 5-Serotoninergic system
One hour after treating rats orally with SMS at a dose of 11 g/kg, 5-HIAA (a serotonin
metabolite) level was elevated gradually in the corpus striatum, with the maximum
level being attained at 4 hr after the treatment. The level of 5-HIAA was still signific-
antly higher than the control at 8 hr after the treatment. The rate of elevation of
Table 2.13 Effects of SMS on the levels of 5-HT metabolites in the corpus striatum and
marginal zone of rats
Time (hr) 5-HIAA

Corpus striatum (nµg/g) Marginal zone (nµg/g)
SMS (11 g/kg,ig) 0 369.0 ± 15.2 410.8 ± 25.4
1 302.0 ± 29.8 442.1 ± 33.1
2 376.2 ± 34.6 479.5 ± 29.0
0 309.8 ± 19.5 405.9 ± 26.8
4 408.7 ± 41.6 528.8 ± 29.5*
8 566.8 ± 36.5** 297.6 ± 35.4*
Table 2.14 Effects of SMS on the levels of NA in the peripheral zone and heart of rats
Time (hr) NA
Peripheral zone (nµg/g) Heart (nµg/g)
SMS (11 g/kg,ig) 0 271.7 ± 16.5 868.8 ± 33.9

1 265.2 ± 6.6 1097.8 ± 77.5**
2 257.7 ± 13.3 879.6 ± 56.5
0 272.4 ± 15.5 875.2 ± 106.2
4 253.7 ± 14.7 877.5 ± 70.5
8 257.0 ± 12.0 873.3 ± 58.1
5-HIAA in the peripheral area was slower than that of the corpus striatum, with a
significant elevation of 45 per cent being at 8 hr after the SMS treatment (Table 2.13)
(Liu et al. 1990).
C. Noradrenergic system
One hour after the oral treatment with SMS at a dose of 11 g/kg, the noradrenaline
(NA) level was significantly elevated in the rat heart, but the effect only lasted for 2 hr,
with the NA level being returned to normal. The level of NA in the peripheral zone of
proencephalon did not show any significant changes (Table 2.14) (Liu et al. 1990).
In summary, oral treatment of rats with SMS (11 g/kg) could significantly decrease
the level of DA in the peripheral zone of proencephalon, while the levels of DOPAC
and HVA (DA metabolites) as well as 5-HIAA (serotonin metabolite) were signific-
antly elevated. This may be related to the emptying action produced by SMS on
monoamine neurotransmitters. Monoamine neurotransmitters were released from the
storage site and then metabolized by monoamine oxidase in neurons, both of which
were manifested as a decrease in the level of monoamine transmitters and an increase
in the levels of their metabolites. The peripheral zone of proencephalon is closely
related to human emotional and mental activities. The effect of SMS on this peripheral
zone may be related to its sedative effect as well as therapeutic effect on neurasthenia.
When compared with the peripheral zone, the effect of SMS on the corpus striatum
was different. Oral treatment of SMS could significantly increase the levels of dopamine
and its metabolites (DOPAC and HVA) in the corpus striatum. These results indi-
cated that SMS could enhance the dopamine synthesis and metabolism, as well as its
exchange rate, resulting in the enhancement of dopaminergic neuron related brain
functions. In addition, oral treatment with SMS could significantly increase the level
of serotonin metabolite (5-HIAA) in the corpus striatum and the peripheral zone of
the rat brain. This may be related to the enhanced exchange rate of serotonin, which is
involved in mental activities and endocrine functions. Plausibly, some pharmacologi-
cal actions produced by SMS may be attributed to its modulatory action in the
functioning of the CNS (Liu et al. 1990).
IMMUNE SYSTEM
I. Phagocytic function of mononuclear phagocyte system (MPS)

in mice
According to the carbon particle clearance method of Biozzi (Williams et al. 1976), mice
were given Indian Ink (tail, iv) at a dose of 0.16 mg/g. At 30 and 300 sec following
the administration, a 20 µl blood sample was taken from the orbital vein. The phagocytic
index was determined by measuring the absorbance of the blood sample at 675 nm. The
results indicated that SMS treatment at a daily intragastric dose of 5.5 or 11.0 g/kg,
consecutively for five days, could produce a dose-dependent stimulatory action in
mouse MPS, with the effect being similar to that of levamisole when given at daily
intraperitoneal dose of 0.01 g/kg (Table 2.15) (Chu et al. 1990).
II. Delayed hypersensitive response in mice

An allergic model was prepared by treating mice with dinitrochlorobenzol (DNCB), and
the intensity of delayed hypersensitive response was determined by noting the weight
difference between the right ear and the left ear. Both oral treatment (11 g/kg) and
intraperitoneal injection (5.5 g/kg) of SMS could produce a very significant stimulatory
effect on the delayed hypersensitive response in mice, with the degree of enhancement
Table 2.15 Effects of SMS on the phagocytic ability of MPS in mice
Dosage (g/kg per day) Amount of ink Number of K ± S.D.

for 5 days (mg/kg) animals
Saline 10.0 160 20 0.0266 ± 0.0012

SMS 5.5 160 20 0.0492 ± 0.0031*
11.0 160 20 0.0553 ± 0.0061**
Levamisole 0.01 160 20 0.0642 ± 0.0048***
*, **, *** p < 0.05, p < 0.01 and p < 0.001 respectively, when compared with the saline group
Table 2.16 Effects of SMS on the reaction to DNCB in mouse ear
Dosage (g/kg) and Number of Mean difference in weight
route of administration animals between the two ears (mg)
Saline 10.0; i.p. 20 32.68 ± 8.22
Levamisole 0.01; i.p. 20 61.31 ± 15.02*
SMS 5.5; i.p. 20 48.7 ± 10.71*‡
11.0; p.o. 20 82.56 ± 19.23*‡
Hydrocortisone-21-sodium
succinate 0.03; i.p. 20 11.91 ± 1.48*
Each value is mean ± S.D.
* p < 0.001 when compared with the saline group
‡ p < 0.01 when compared with the levamisole group
Table 2.17 Effects of SMS on PCA in rats
Dosage (g/kg per day) Number of Absorbance of Evans Blue exudate

and route animals from skin plague (mg)
Saline 10.0; i.p. 10 0.988 ± 0.09

SMS 5.5; p.o. 10 0.402 ± 0.05*
Disodiumcromoglycate 0.03; i.p. 10 0.384 ± 0.04*
Each value is mean ± S.D. (n = 6)
* p < 0.001 when compared with the saline group
produced by oral treatment being higher than that produced by intragastric treatment
with levamisole (10 mg/kg). However, the extent of stimulatory action produced by
the intraperitoneal injection of SMS was significantly lower than that of levamisole
(Table 2.16) (Chu et al. 1990).
III. Passive cutaneous anaphylaxis (PCA) in rats

Passive anaphylaxis was induced in rats by administering anti-IgE serum at a titer of
160. The rats were then exposed to pollen (1 per cent in Evans Blue) at a dose of 2.5
mg/ml given intravenously 48 hr later, and then killed 30 min after the injection. The
Evans Blue exudates from the skin plaque of different groups of rats were measured for
their absorbance. The results indicated that SMS pretreatment (5.5 g/kg/day) could
produce a significant inhibitory effect on PCA in rats, with the degree of inhibition
being comparable to that produced by the positive control disodiumcromoglycate
(0.01 g/kg, i.p.). This suggested that SMS treatment could produce an inhibitory
effect on the IgE antibody-mediated immune responses (Table 2.17) (Chu et al. 1990).
ANTIOXIDANT SYSTEM
The ability of SMS to protect against myocardial damage caused by free radicals in
various experimental and clinical settings suggests the presence of antioxidant activity
(Lu et al. 1994; Rong et al. 1989c; Rong et al. 1989d). An experimental rat model of
carbon tetrachloride-induced hepatic damage was used for detecting the in vivo anti-
oxidant activity of SMS, in which oral treatment of SMS at a daily dose of 24 g/kg for
3 days was found to inhibit the carbon tetrachloride-induced damage in rats (Yick et al.
1998). The protection was associated with an enhancement on hepatic antioxidant status,
particularly the glutathione related antioxidant system (Yick et al. 1998). On the other
hand, using a rat model of myocardial ischemia reperfusion injury, SMS (24 g/kg/day,
3 days, ig) was shown to be able to protect the heart from free radical-mediated damage,
possibly through enhancing the myocardial glutathione antioxidant status (Li et al.
1996). In addition, pretreating rats with SMS by direct injection into the duodenum
2 hours prior to cerebral ischemia induced by bilateral carotid artery occlusion suppressed
lipid peroxidation and prevented the inhibition of glutathione peroxidase activity
associated with ischemia reperfusion (Xuejiang et al. 1999). Interestingly, it was found
that SMS treatment could produce beneficial effects on the ischemic-reperfused brain
tissue even when it was administered 45 minutes after post-ischemic reperfusion. The
ability of SMS to non-specifically enhance tissue antioxidant status suggests its preventive
effect on aged-related diseases, particularly coronary heart disease and neurological
disorders such as Parkinson’s disease and Alzheimer’s disease, all of which involve free
radical-mediated reactions in the pathogenic process.
Using in vivo and in vitro assay systems, it has been shown that the antioxidant
activity of SMS is derived mainly from Fructus Schisandrae (FS) (Ko et al. 1995c). A
novel compound, 5-hydroxymethyl-2-furaldehyde, presumably arising from chemical
interaction among chemical constituents derived from FS and Radix Ophiopogonis dur-
ing the decoction process, was also found to possess cardioprotective and antioxidant
activity (Yan et al. 1998). In an effort to identify the active principle(s) and define
the antioxidant mechanism of SMS, the activity-directed fractionation of FS was per-
formed and subsequently obtained a lignan-enriched extract that could enhance hepatic
glutathione status in rats (Ko et al. 1995b). The beneficial effect of the lignan-enriched
FS extract on hepatic glutathione status was evidenced by a generalized protection
against hepatotoxicity induced by carbon tetrachloride (Ko et al. 1995b), cadmium
chloride and aflatoxin (Ip et al. 1996). With regard to the molecular mechanism involved
in the FS-induced enhancement of hepatic glutathione antioxidant status, experimental
results suggested the possible involvement of facilitation of reduced glutathione (GSH)
regeneration via the glutathione reductase-catalyzed and NADPH-mediated reactions
(Ko et al. 1995a). The enhanced GSH regeneration can, in turn, promote the GSH-
mediated antioxidant reactions. These findings are consistent with the observation that
SMS pretreatment could increase hepatic GSH level as well as glucose-6-phosphate
dehydrogenase activity in carbon tetrachloride intoxicated rats (Yick et al. 1998).
In addition, schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from
FS, has been found to protect against free radical-mediated hepatic (Ip et al. 1995),
myocardial (Yim and Ko 1999) as well as cerebral damage (Ko and Lam 2002). The
protective effects were associated with the enhancement in tissue glutathione antioxidant
status, particularly in the mitochondrion (Ip and Ko 1996). In addition, modulations
in tissue level of non-enzymatic antioxidants such as ascorbic acid and α-tocopherol,
which may be an effect secondary to the enhancement of tissue glutathione status,
were also observed (Ip and Ko 1996; Ko and Yiu 2001). Given the tissue non-specific
enhancing effect of Sch B on glutathione antioxidant status, a fundamental protect-
ive mechanism, such as heat shock protein (Hsp) induction, may be involved in tissue
protection. In this regard, a recent study has demonstrated that Sch B pretreatment
produced a dose-dependent increase in hepatic Hsp 70 level in mice and protection
against tissue necrosis factor-alpha induced hepatic apoptosis in D-galactosamine
sensitized mice (Ip et al. 2001). In conclusion, Sch B, a major antioxidant constituent
present in SMS, can produce tissue non-specific protective effect against oxidative damage
by virtue of a yet not clearly defined molecular mechanism. Further works are under
way in our laboratory along this line of research.
OTHERS
I. Respiration, electrocardiogram and blood pressure
A. Effect on respiration in rats

When anesthetized rats were given duodenal instillation of SMS at doses of 11 and
44 g/kg, the respiratory frequency was increased by 8 and 12 per cent respectively,
indicative of a slight stimulatory action on respiration, 30 min following the treat-
ment. This stimulatory action may be useful for enhancing the respiratory function of
the body under shock conditions or in aged people (Zai et al. 1990).
B. Effect on electrocardiogram (ECG)

After the duodenal instillation with SMS at a dose of 11 or 44 g/kg, ECG from the
treated animals indicated that there were no detectable changes in the ventricular rate
(R-R period) or the time for atrioventricular conduction (P-R period). On the other
hand, the T-wave was significantly amplified and the OTC duration was prolonged.
These observations suggested that SMS could produce negative inotropic action with
the prolongation of OTC duration, which is important to the protection against
myocardial infarction and arrhythmias (Zai et al. 1990).
C. Effect on blood pressure

Anesthetized rabbits were given SMS by an intravenous injection at doses of 1.1 and
2.2 g/kg. The blood pressure did not show any detectable changes. Rabbits given SMS
by duodenal instillation at the same dosage did not show any fluctuations in blood
pressure either (Zai et al. 1990).
II. Hemodynamics
An adult dog (8.5–15 kg) was anesthetized by intravenous injection with pentobarbital
(30 mg/kg), the chest was then opened to expose the heart. A multi-channel physio-
logical recording and electromagnetic flow meter were used for continual monitoring
of the hemodynamic parameters. Intravenous dripping (3.6 ml/min) with SMS at a
dose of 1.1 g/kg could produce a negative inotropic effect on the canine heart, which
was associated with the decrease in left ventricular internal pressure, myocardial
contractile rate and heart rate. The end pressure during left ventricular diastole was
found to increase. This may be due to the fact that under negative inotropic status, the
Table 2.18 Effects of SMS on the enhancement of micronucleus by cyclophosphamide
Dosage
Number of Cyclophospamide SMS (p.o.) Micronucleus
animals (i.p) (g/kg per day) frequency (%)
(mg/kg per day) (mean ± S.D.)
Control 17 2.06 ± 1.52
Cyclophosphamide 17 50 × 2 19.35 ± 7.75*
Cyclophosphamide + SMS 18 50 × 2 14 × 10 13.80 ± 7.51†
Control 10 2.00 ± 1.49
Cyclophosphamide 8 50 × 2 26.20 ± 5.33*
Cyclophosphamide + SMS 7 50 × 2 28 × 10 17.70 ± 10.13
† p < 0.05 when compared with the cyclophosphamide group
cardiac pumping function was impaired, causing the increase in residual blood volume
of the left ventricle during diastole, which in turn increased the end pressure during
diastole. Results from the experiment also demonstrated that SMS could enhance
the cardiac output, coronary flow and vastus arterial flow, but reduce the total peri-
pheral resistance, coronary resistance and vastus arterial resistance. These alterations,
which can facilitate the distribution and local supply of blood inside the body, sug-
gested that SMS had the ability to produce a vasodilating effect and reduce blood
vessel resistance. On the other hand, lowering of cardiac rate and enhancement of
coronary flow, together with the reduced coronary resistance can enable the sufficient
perfusion of myocardial tissue, which in turn, further improves the blood circulation
(Li et al. 1990a).
III. Tissue protection against toxic agents
A. Effect on mutagen-induced chromosomal damage in mice

Cyclophosphamide given to mice at a daily dose of 50 mg/kg for two days could cause
chromosomal damage associated with an enhanced rate of micronucleus formation in
bone marrow. Mice treated with SMS orally at a daily dose of 14 g/kg for 10 days
could inhibit the cyclophosphamide-induced chromosomal damage, with the rate of
micronucleus formation being significantly reduced (Table 2.18).
B. Effect on cigarette smoke-induced lung damage in mice

Mice were smoked by ten or twenty ignited cigarettes for 45 min twice a day (in
the morning and afternoon,) for ten consecutive days. Lung tissue of the cigarette
smoke-intoxicated mice were taken for tissue sectioning and microscopic examina-
tion. Results from microscopic examination indicated that the adhesive membrane in
pulmonary bronchioles of control mice were intact, without any upper epithelial pro-
liferation. In addition, no inflammatory cell infiltration was found in the inner and
outer wall of bronchioles, and the size of alveolar sac was normal. In contrast, smoke-
intoxicated mice had thicker bronchiolar walls, with more lymphocyte infiltration at
Table 2.19 Elevation of white blood cell count by SMS
Dosage
Number of WBC suppressant SMS (p.o.) WBC count (mm−3)
animals (mg/kg per day) (g/kg per day) (mean ± S.D.)
Control 15 8480 ± 3195
Cyclophosphamide 15 40 × 5 (i.p.) 1990 ± 850**
Cyclophosphamide + SMS 14 40 × 5 (i.p.) 14 × 7 3150 ± 1005‡
Hydrocortisone 14 40 × 5 (i.p.) 3100 ± 1760*
Hydrocortisone + SMS 14 40 × 5 (i.p.) 14 × 7 5896 ± 3287‡
** p < 0.001 when compared with the control
‡ p < 0.01 when compared with the cyclophosphamide or hydrocortisone group
the peripheral region, and the upper epithelium of the bronchiolar adhesive membrane
had proliferated into a nipple-liked shape. The lung tissue of cigarette smoke intoxic-
ated mice also showed signs of diffuse emphysema. Pulmonary bronchioles isolated
from mice treated orally with SMS at a daily dose of 14 g/kg for ten days, was found
to be basically normal, without any inflammatory cell infiltration being observed.
However, the lung tissue had diffuse emphysema. These observations indicated that
SMS could significantly inhibit the inflammation caused by cigarette smoke, but
could not improve the condition of pulmonary emphysema caused by cigarette smoke
(Hang et al. 1990).
C. Effect on cyclophosphamide and prednisone-induced leukopenia in mice

Cyclophosphamide or prednisone given at a daily dose of 40 mg/kg for five days by
intraperitoneal or intramuscular injection respectively, could significantly deplete
the white blood cell count in mice. Treating mice orally with SMS at a daily dose of
14 g/kg for a week two days prior to the administration of the toxins could signific-
antly prevent the depletion of white blood cell counts caused by cyclophosphamide
and prednisone (Table 2.19) (Hang et al. 1990).
IV. Biochemical changes of hepatic tissue in aging rats

Aging rats were treated intragastrically with SMS at a daily dose of 10 g/kg, for three
consecutive weeks. Histochemical analysis on hepatic tissue samples indicated that
SMS treatment enhanced the response of hepatic sorbitol dehydrogenase, but slightly
reduced the responses of both LDH and monoamine oxidase (MAO). The number of
glycogen staining responses with intermediate intensity was increased. RNA response
was also significantly enhanced. These observations suggested that SMS treatment could
increase the hepatic energy metabolism and hence the body vitality, and facilitate the
hepatocellular function. All these actions are no doubt beneficial for the improvement
of age-related conditions. The relative small effect produced by SMS treatment on LDH
and MAO suggested that SMS might not affect the hepatic anaerobic metabolism and
the decomposition of monoamines (Zhang et al. 1990b).
CONCLUSIONS
The prescription of multi-component (compound) formulation is a major means for

the treatment of diseases in the clinical practice of Chinese Medicine. It is widely
accepted that compound formulation, which constitutes one of the crucial components
in the wealth of Chinese Medicine, embodies the holistic theory in Chinese Medicine.
Clinical practices have long shown that compound formulation is superior to single drug
(herb) treatment in regard to its specific therapeutic efficacy. Extensive experimental
and clinical investigations on famous traditional Chinese formulations with prudent
therapeutic efficacy have important implications in defining the scientific rationale for
the theory in Chinese medicine. In addition, these works can also lead to the develop-
ment of novel Chinese formulation-based pharmaceutical preparations, which maintain
the characteristic therapeutic efficacy of compound formulation.
Pharmacological studies of SMS indicate that it can produce effects on the cardio-
vascular system, central nervous system, immune system, antioxidant system, as well
as the ability to resist toxin-induced tissue injury. Given the effect of SMS on the
metabolism of monoamine neurotransmitters in the brain and heart of experimental
animals, it is likely that the pharmacological effects produced by SMS may, at least in
part, be attributed to its integrative action in the CNS and the peripheral effector
organs. When taken together, SMS treatment results in the modulation of body func-
tions for the prevention and treatment of diseases.
REFERENCES
Beijing College of Traditional Chinese Medicine (1973) Effect of SMS on the myocardial
ATPase activities in rats and guinea pig, Xin Yiyaoxue Zazhi, 10, 387.
Blodel, B., et al. (1971) Heart cells in culture: a simple method for increasing the proportion
of myoblasts, Experientia, 15, 356.
Chu, Y., Cai, S.H., Zhang, L., et al. (1990) Shock-arresting and immuno-modulatory effects of
SMS. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.146–60.
Hang, B.Q., Wu, G.Z., Wu, Y., et al. (1990) Effect of SMS on lung damage. In Y.Q. Yan
(ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.198–206.
Higgins, T.T.C., et al. (1980) The effect of extracellular calcium concentration and Ca antago-
nist drugs on enzyme release and lactate production by anoxic heart cell cultures, J. Mol.
Cell. Cardiol., 12, 909.
Hou, D.H., Li, L., Wang, Q.J., et al. (1990) Effects of SMS on experimentally-induced arrhy-
thmia. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.140–5.
Ip. S.P., Wu, S.S., Poon, M.K.T., et al. (1995) Effect of Schisandrin B on hepatic glutathione
antioxidant system in mice: Protection against carbon tetrachloride toxicity, Planta Med.,
61, 398–401.
Ip, S.P., Ko, K.M. (1996) The crucial antioxidant action of schisandrin B in protecting against
carbon tetrachloride hepatotoxicity in mice. A comparative study with butylated hydro-
xytoluene, Biochem. Pharmacol., 52, 1687–93.
Ip, S.P., Mak, D.H.F., Li, P.C., Poon, M.K.T., et al. (1996) Effect of Schisandra Chinensis on
aflatoxin B1 and cadmium chloride induced hepatotoxicity in rats, Pharmacol. Toxicol., 78,
413–6.
Ip, S.P., Che, C.T., Kong, Y.C., et al. (2001) Effects of schisandrin B pretreatment on tumor
necrosis factor-α induced apoptosis and Hsp70 expression in mouse liver, Cell Stress &
Chaperones, 6, 44–8.
Ko, K.M., Mak, D.H.F., Li, P.C., et al. (1995a) Enhancement of hepatic glutathione regenera-
tion capacity by a lignan-enriched extract of Fructus Schisandrae in rats, Jpn. J. Pharmacol.,
69, 439–42.
Ko, K.M., Ip., S.P., Poon, M.K.T., et al. (1995b) Effect of a lignan-enriched Fructus Schisandrae
extract on hepatic glutathione status in rats: Protection against carbon tetrachloride toxicity,
Planta Med., 61, 134–7.
Ko, K.M., Yick, P.K., Poon, M.K.T., et al. (1995c) Schisandra chinensis-derived antioxidant
activities in Sheng Mai San, a compound formulation, in vivo and in vitro, Phytotherapy Res.,
9, 203–6.
Ko, K.M., Lam, B.Y.H. (2002) Schisandrin B protects against tert-butylhydroperoxide induced
cerebral toxicity by enhancing glutathione antioxidant status in mouse brain Mol. Cell.
Biochem. (in press).
Ko, K.M., Yiu, H.Y. (2001) Schisandrin B modulates the ischemia-reperfusion induced changes
in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Mol. Cell. Biochem., 220,
141–7.
Li, H., Hong, S.W., and Peng, Q (1990) Effect of SMS on the hemodynamics of dogs under
opened-chest study. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.166–8.
Li, L.D, Liu, J.X., Wang, R.X., et al. (1990a) Effects of SMS on experimentally-induced heart
failure in dogs. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.100–5.
Li, L.D., Sun, H., Gao, F.H., et al. (1990b) Effects of SMS on cardiomyocytes under acute heart
failure in vitro. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.128–33.
Li, L.D., Sun, W., Wang, R.X., et al. (1990c) Effects of SMS on cardiac ischemia and heart
failure in rats. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.116–27.
Li, P.C., Mak, D.H.F., Poon, M.K.T., et al. (1996) Myocardial protective effect of Sheng Mai
San (SMS) and lignan-enriched extract of Fructus Schisandrae, in vivo and ex vivo,
Phytomedicine, III, 217–21.
Liu, G.Q., Xie, L., and Liu, X.Q. (1990) Effect of SMS on the monoamine neurotransmitters.
In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.235– 42.
Liu, Y.G. et al. (1978) Effect of Shengmai San (SMS) on the DNA metabolism of cardiac
muscle, Shanxi Xin Yiyao, 4, 6.
Lu, B.J., Rong, Y.Z., and Zhao, M.H. (1994) Antioxidation effect of SMS on patient with
acute myocardial infarction, Chinese Journal of Integrated Traditional and Western Medicine, 14,
712– 4.
Rong, Y.Z., et al. (1983) Ultrastructural changes in adriamycin-induced cardiotoxicosis,
J. Mol. Cell Cardiology, 15(Supp. 14), 30.
Rong, Y.Z., et al. (1989) Protection against adriamycin-induced cardiotoxicity by Shengmai
San, Chinese Journal of Cardiology, 17, 371.
Rong, Y.Z., Wen, W., and Fu, L. (1989) Protective effect of Shengmai San on adriamycin-
induced cardiotoxicity – an experimental study, J. Shanghai Second Medical School, 3, 39– 43.
Rong, Y.Z., Wen, W., and Fu, L. (1989) Protective effect of Shengmai San on adriamycin-
induced cardiotoxicity – an experimental study, J. Shanghai Second Medical School, 3, 39– 43.
Rong, Y.Z., Wen, W., and Yao, M. (1989) Role of oxygen radical in myocardial reoxygenation
injury and the protective effect of Shengmai San, J. Shanghai Second Medical School, 3, 11–5.
Shi, L., Fan, P.S., Fang, J.X., et al. (1990) Effects of SMS on serum lipid and lipoprotein levels
in experimentally-induced atherosclerosis. In Y.Q. Yan (ed.), Integrated Study of Shengmai San
Tonic, CMPSP, China, p.168–79.
Smith, R.L. and Hilker, D.M. (1973) Experimental dietary production of aortic atherosclerosis
in Japanese quail, Atherosclerosis, 17, 63.
Sun, H., Liu, Z.Y., Gao, F.H., et al. (1990) Protective effect of SMS on toxin-induced myocardial
injury. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.180–5.
The Pathophysiology and Anatomy Research Groups of The school of Basic Medical Sciences of
Beijing Medical University (1974) A reproducible model of cardiogenic shock in rabbits,
Journal of Beijing Medical University, 6(4), 241.
The Pathophysiology Research Group of The school of Basic Medical Sciences of Beijing
Medical University (1975) Effect of the treatment of cardiogenic shock with SMS in rabbits,
Journal of Beijing Medical University, 7(2), 118.
Wang, R.X. and Li, L.D. (1990) Scientific bases for the formulation of SMS. In Y.Q. Yan (ed.),
Integrated Study of Shengmai San Tonic, CMPSP, China, p.12–25.
Williams, C.A., et al. (1976) Blood stream clearance of carbon. In Methods in Immunology and
Immunochemistry, V, Academic Press, New York, p.294.
Xuejiang, W., Magara, T., and Konishi, T. (1999) Prevention and repair of cerebral ischemia-
reperfusion injury by Chinese herbal medicine, Shengmai San, in rats, Free Radical Research,
31, 449–55.
Yan, Y., Zhu, D., Li, Z., et al. (1998) Relationship between component changes and efficacy of
Sheng mei san: V. Isolation, identification and content changes of 5-HMF, Academic Periodic
Abstracts of China, 4, 865–8.
Yick, P.K., Poon, M.K.T., Ip, S.P., et al. (1998) In vivo antioxidant mechanism of ‘Sheng Mai
San’, a compound formulation, Pharmaceutical Biology, 36, 189–93.
Yim, T.K., Ko, K.M. (1999) Schisandrin B protects against myocardial ischemia-reperfusion
injury by enhancing myocardial glutathione antioxidant status. Mol. Cell. Biochem., 196,
151–6.
Yuan, H.N., et al. (1985) Introduction to the GJ-series 3-channel mouse activity recorder, Acta
Pharmacologica Sinica, 1, 49.
Yuan, H.N. and Zhang, Q. (1990) Effect of SMS on the central nervous system. In Y.Q. Yan
(ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.212–8.
Zai, D.Z., Song, P., and Wang, L.Y. (1990) Effects of SMS on the respiratory system, cardiogram
and blood pressure. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.160–5.
Zhang, B.H., Yao, J.A., Zong, Q., et al. (1990) Effects of SMS on ischemic heart diseases. In
Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China, p.133–9.
Zhang, G.X., Liu, Z.Y., Li, C.X., et al. (1990) Effect on the chemical composition of the liver
in aged rats. In Y.Q. Yan (ed.), Integrated Study of Shengmai San Tonic, CMPSP, China,
p.206–12.
Zhang, Y.C. (1996), Mechanism of adriamycin-induced cardiomyopathy and its protection,
Ph.D Thesis, Shanghai Second Medical University.
Zhao, L.G., et al. (1974) Prevention of acute heart dysfunction by SMS injection, Tianjin
Medical Journal, 2, 449.
Zhuang, S.F., Yan, Y.Q., Zhu, D.N., et al. (in press) Effect of SMS and its active ingredients on
viral myocaditis.
Clinical studies 41
3 Clinical studies on Shengmai San

Ye-Zhi Rong, Mei-Hua Zhao, Bao-Jing Lu,
Xiang-Yang Zhu, Shang-Biao Lu, Ya-Chen
Zhang, Jie Chen [Translated by Kam-Ming Ko]
CORONARY HEART DISEASE
Shengmai San (SMS), a well-known traditional Chinese medicine (TCM) formula,

has been prescribed for replenishing the Qi (vital energy), recuperating the pulse,
rescuing patients from emergency and relieving from collapse. The Ancient Chinese
also used SMS for the treatment of ‘chest bi-syndrome’ and ‘cardialgia’. With the recent
advances in medical sciences and technology, particularly in the area of integration
of Chinese and modern medicine, the complement of TCM with modern medicine,
and vice versa, in terms of theory and practice has allowed the exploration into the
wealth of TCM. The clinical applications of SMS have been expanded not only by
the introduction of new dosage form, but also by the increased understanding of the
mechanisms involved in the prevention and treatment of diseases afforded by SMS
treatment (Cong 1980). Nowadays, SMS is widely accepted as one of the effective drugs
for the prevention and treatment of coronary heart disease (CHD) in China, particu-
larly for patients with myocardial malfunction (Qiu and Luo 1989). Nevertheless,
fundamental differences in the theory between TCM and modern medicine have led
to discrepancies in diagnosis and treatment for the same or basically similar diseases.
These differences produce inconsistencies between TCM and modern medicine in the
definition and nomenclature for certain diseases, like ‘chest bi-syndrome’ and ‘cardialgia’
versus CHD. Hence, the complementary benefits derived from the integration of TCM
and modern medicine can definitely facilitate the upgrading of scientific research and
therapeutic efficacy of TCM. The investigation of mechanisms involved in the preven-
tion and treatment of CHD by SMS and its clinical applications will be described in
the following sections.
I. Definition and clinical classification of CHD

Coronary heart disease is defined as coronary atherosclerotic heart disease. It is the
heart disease induced by myocardial ischemia originating from the blockage of blood
vessels due to coronary atherosclerosis. Together with the functional changes of the
coronary arteries such as coronary spasm, they are collectively named as CHD.
In general CHD can be diagnosed by electrocardiogram, coronary arteriography,
radioactive isotopes and ultrasonic cardiography, laboratory blood tests and clinical
manifestations. The World Health Organization has classified CHD into five clinical
types: (1) latent; (2) angina pectoris; (3) myocardial infarction; (4) heart failure and
arrhythmia and (5) sudden death.
42 Ye-Zhi Rong et al.
II. Pathogenesis of CHD
According to modern medicine, the mechanism involved in the pathogenesis of CHD
is multifactorial and has not yet been completely defined. Some important pathogenic
processes are described as follows.
A. Fatty infiltration
Research studies have demonstrated that the lipid content of atherosclerotic plaque
residing in the coronary arterial wall is mainly derived from plasma. Plasma cholesterol,
triglycerides and phospholipids are incorporated with apoproteins to form lipoproteins
for their dissolution and transportation in blood. The low-density lipoprotein (LDL)
mainly consists of cholesterol and cholesterol esters, whereas the very low-density
lipoprotein (VLDL) is mainly composed of triglycerides. The increase in plasma lipids
arising from the disorder in lipid metabolism can lead to the infiltration of lipids,
through the endothelial cells, into the arterial wall. The entry of lipoproteins into the
middle layer of the arterial wall will cause the proliferation of smooth muscle cells and
their migration towards the arterial intima. The smooth muscle cells and monocytes
will then engulf a huge amount of lipids and be converted to foam cells, which, in
turn, lead to the formation of a fatty streak, the earliest detectable clinical sign of
atherosclerosis. The events, including proliferation of smooth muscle cells, accumulation
of connective tissues, disposition of lipids and proliferation of fibrous tissue, finally
culminate in the formation of atherosclerotic plaque.
B. Aggregation of blood platelets and thrombosis

Recently, it has been reported that injuries to the arterial intima will cause the
adhesion and aggregation of blood platelets at the injured site. The blood platelets
then release active agents that can stimulate the proliferation of smooth muscle cells
and endothelial cells, as well as the disposition of fibrous proteins. All these eventu-
ally lead to the formation of a micro-thrombus at the injured site. The thrombus will
then be covered by the newly proliferated endothelial cells and becomes part of the
arterial wall. The blood platelets and white blood cells inside the thrombus will be
disrupted, with the lipid content being released. These lipids, together with those being
deposited from the plasma, eventually lead to the formation of atherosclerotic plaque.
Thrombosis without the deposition of plasma lipids will not lead to the formation of
atherosclerotic plaque.
C. Response to injury
Hypertension and erratic blood flow created by arterial branching and localized narrow-
ing of blood vessels can produce hemodynamic changes associated with turbulence and
shear stress. These hemodynamic disturbances, together with other factors such as the
protracted and recurrent noxious effects caused by bacterial and viral infection, toxins,
immunogenic factors, vasoactive substances, vasoconstrictive substances and lipid oxidat-
ive damage, can produce injuries to the arterial intima as well as functional changes to
blood vessels. These, in turn, facilitate the lipid deposition, adhesion and aggregation
of blood platelets and finally result in the formation of atherosclerotic plaque.
Clinical studies 43
D. Clone theory
The pathogenesis of atheroclerosis involves the proliferation of smooth muscle cells and
their engulfment of lipids. Some growth factors, such as blood platelet-derived growth
factor and endothelium derived growth factor, can accelerate both the proliferative
process and migration of smooth muscle cells, finally leading to the formation of
atherosclerotic plaque.
E. Others
Other mechanisms involved in the pathogenesis of CHD include the changes in neural
factors, sex hormones and endothelial function and a decrease in the activity of enzymes
located in the arterial wall. Polygenetic inheritance and environmental factors may be
also involved.
III. Historical aspects in the clinical applications of SMS

According to the medical reports from Ming and Ching Dynasty in China, SMS is capable
of benefiting the Qi (vital energy) and expelling the heat in summer. It was therefore
prescribed for heat-induced damage of the Qi and the deficiency of both the Qi and
the Yin caused by the depletion of the Yin-fluid (body fluid ), with symptoms of pro-
fuse sweating, thirst, tiredness, shortness of breath, palpitation, weak pulse, and red
and dry tongue without saliva. SMS was later used for treating some severe and life-
threatening syndromes, like deficiency of primordial-Qi, profuse perspiration associated
with Yang deficiency, coughing and dyspnea due to lung-asthenia, and weak and faint
pulse conditions. With the rapid advance in the integration of TCM and modern
medicine for the prevention and treatment of cardiovascular diseases since the beginning
of the 1970s in China, extensive experimental and clinical investigations have been
done for SMS. In 1973, Tianjin Nankai Hospital (1973) reported that SMS, when
given orally or by intravenous infusion, could significantly elevate the blood pressure
and hence protected against the shock state in patients suffering from myocardial
infarction. The treatment regimen could also produce positive inotropic action in
patients with heart failure. Starting in the late 1970s, some hospitals, particularly
those in Beijing and Shanghai, began to use SMS for the treatment of ‘chest bi-syndrome’
and ‘cardialgia’, which is equivalent to angina pectoris and myocardial infarction,
respectively. Some hospitals and pharmaceutical manufacturers in Chengdu adopted
modern pharmaceutical technologies to prepare dosage form such as intravenous injec-
tion liquid or oral liquid for SMS. These preparations were used in animal experiments
and clinical studies for investigating the efficacy of SMS. In the mid 1980s, the State
Science and Technology Commission (now known as the Ministry of Science and
Technology) and the State Drug Administration of China established a nationwide
strategic cooperative team for the research and development of SMS. A diverse range
of animal studies have been done using SMS oral liquid, and the clinical efficacy on
angina pectoris and cardiomyopathy as well as on retarding the aging process have
also been examined. In 1992, the State Chinese Medicine Authority regarded SMS
injection liquid as the first batch of essential medication in the emergency room of
TCM hospitals. In 1994, the State Administration of Traditional Chinese Medicine,
China, established a cooperative team for emergent ‘chest bi-syndrome,’ which coordinated
all clinical studies from six hospitals in Beijing, Shanghai and Chengdu on evaluation
of clinical efficacy of SMS on angina pectoris as well as the related animal studies. In
1995, a comprehensive report was made for 219 case studies on angina pectoris and
other related studies on SMS, and the overall result was encouraging (SATCM, China,
1995).
Nowadays, the scope of indications for SMS has been widened. SMS can be used not
only for the treatment of cardiovascular diseases, such as CHD (angina pectoris and
myocardial infarction), heart malfunction, cardiogenic shock, arrhythmia, sick sinus
syndrome, myocarditis and cardiomyopathy, but also for improving conditions of the
Qi and Yin deficiency caused by heart surgery, cardiopulmonary diseases, septic shock,
epidemic hemorrhagic fever and cancer chemotherapy. In addition, SMS can also pro-
duce anti-aging effects.
IV. Experimental studies and clinical applications of SMS

In the past three decades, a huge amount of experimental evidence concerning SMS has
been accumulated. Currently, SMS is clinically used for the treatment of both Qi and
Yin deficiency associated with various cardiovascular diseases. The better understand-
ing of the mechanisms involved in the pharmacological actions of SMS has enabled a
more favorable clinical outcome of SMS treatment in CHD to be achieved. Some of the
important findings are described as follows.
A. Free radical scavenging and anti-lipid peroxidation effects: prevention

and treatment of myocardial ischemia-reperfusion injury
Recently, free radical-mediated reactions and lipid peroxidative damage have been
implicated in the pathogenesis and development of CHD (Yao et al. 1988; Huang
et al. 1993). Free radicals are involved in the formation of atherosclerotic plaque
through oxidatively modifying the LDL. The abrupt increase in lipid peroxidative pro-
ducts during the atherosclerotic process can damage the arterial endothelial cells, which
will, in turn, accelerate the progress of atherosclerosis. Meanwhile, the lipid peroxidat-
ive reactions can alter the lipid components of membrane bound enzymes, receptors
and ion channels, leading to functional impairment of these proteins. Transmembrane
lipid peroxidation can produce new ion channels, which are highly permeable to calcium
ions, resulting in intracellular calcium overload. Superoxide radical (O2•− ) and hydroxyl
radical (•OH) are reactive oxidants that can indirectly or directly cause oxidative chain
reactions in membrane lipids, resulting in the formation of malondialdehyde (MDA),
one of the end-products of lipid peroxidation. Under normal conditions, the cellular
antioxidant defense system can protect against free radical-mediated oxidative damage.
Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the important
enzymatic components of the antioxidant defense system, can prevent the formation
of •OH by removing O2•− and H2O2 as well as terminate the propagation of lipid
peroxidation reactions by converting the oxidized lipid molecules into non-oxidative
hydroxyl compounds.
A comparative study between 98 cases of CHD and 110 healthy individuals, as
described by Lu et al. (1994), has demonstrated that SOD and GSH-Px activities were
significantly lower and MDA level was significantly higher in the blood of CHD
patients. The decrease in GSH-Px activity and the increase in MDA level were more
Clinical studies 45
apparent in patients with myocardial infarction (68 cases), when compared with those
with angina pectoris (30 cases). These observations suggested that under conditions of
myocardial infarction, the increased extent of myocardial ischemia could enhance the
free radical production and hence the lipid peroxidation reactions. The free radical-
mediated lipid peroxidation reaction is an important factor involved in the pathogenesis
and development of CHD (Lu et al. 1994). In the same study, patients with myocardial
infarction were randomly divided into groups: (1) standard treatment and (2) standard
treatment plus SMS treatment. SMS was given orally in the form of granules, with
3 packs per day (one pack contains Radix Ginseng (1 g), Radix Ophiopogonis (3 g) and
Fructus Schisandrae (1.5 g)), consecutively for 28 days. The results indicated that after
2 weeks of standard treatment plus SMS, the patients were found to have higher blood
SOD and GSH-Px activities than those of patients receiving only the standard treat-
ment per se, with significant increase in enzyme activities being observed four weeks
after the SMS treatment (Lu et al. 1994). These findings indicated that SMS treatment
could enhance antioxidant defense and inhibit lipid peroxidation in patients suffering
from myocardial infarction. However, the mechanism involved in the beneficial effect
produced by SMS treatment remains unclear. Research studies on individual herbs
indicated that saponin isolated from Ginseng could suppress the free radical production
from activated polymorphonuclear leukocytes and neutrophils, while lignans isolated
from Schisandrae could reduce the extent of lipid peroxidation.
During the procedure of open-heart surgery, a myocardial tissue sample was taken
from the post-ischemic heart after 30-min of reperfusion for microscopic examination.
It was found that myocardial tissue obtained from patients treated with SMS prior
to surgery were found to have a smaller degree of ultrastructural damage when com-
pared with the control. Plasma creatine phosphokinase isozyme (CPK-MB) activity in
SMS-treated patients was also lower than that of the control 12 and 24 hours after the
surgery (Li et al. 1994).
B. Effects on myocardial energy metabolism, intolerance to ischemia

and infarct size
A huge volume of clinical data indicated that the decrease in exercise-tolerance is
not only directly correlated with the occurrence of cardiogenic shock in patients suffer-
ing from CHD, but also predictive to an impaired quality of life during the course
of the disease (Deng and Luo 1992; Pathophysiological Research Group, Beijing
Medical University 1977). Exercise-tolerance or exercise capacity is a factor independ-
ent of changes in the ST segment of the electrocardiogram or the extent of patho-
logical changes in the coronary artery that affects the survival of a patient with CHD.
It is usually expressed as maximal oxygen consumption (VO2max). VO2max indicates
the largest capacity of the body in the delivery and hence utilization of oxygen under
exercise conditions. A study conducted in Xin-Hua Hospital has examined the short-
term effect of SMS injection liquid on the exercise-tolerance of patients suffering from
angina pectoris. Twenty-seven patients with angina pectoris, capable of doing flat-
board exercise, were randomly divided into the SMS pretreated group and Danseng
(Radix Salviae Miltiorrhizae) pretreated group. SMS or Danseng pretreatment was done
by intravenous infusion at a daily dose of 80 and 16 ml, respectively, consecutively for
fourteen days. After the drug pretreatment, both groups were assessed for the ability
to perform flat-board exercise and the maximal oxygen consumption was computed
as metabolic capacity. The results indicated that patients given SMS injection liquid
were found to have significantly increased VO2max when compared with the Danseng
group. The electrocardiogram of patients given with SMS injection liquid was also
significantly improved, as indicated by the prolongation in the consecutive exercise
period and the time delay for the suppression of the ST segment by 1 mm. The recovery
time for the ST segment and the absolute value at maximum suppression of the ST
segment were also decreased. These observations indicated that SMS injection liquid
was superior to that of Danseng, as assessed by exercise-tolerance and the extent of
myocardial ischemia in patients with angina pectoris. As described in Li et al. (1999),
patients suffering from angina pectoris, as diagnosed by coronary arteriography, were
subjected to a flat-board exercise test, before and after the treatment with SMS injec-
tion liquid. The results indicated that pretreatment with SMS was able to improve
heart function, enhance exercise-tolerance, reduce the total sum of ST segment sup-
pression measured at various leads, and ameliorate the extent of myocardial ischemia
in patients suffering from angina pectoris under exercise conditions (Li et al. 1999).
Numerous clinical studies on the therapeutic effect of SMS preparations on acute
myocardial infarction have been reported. Regardless of the presence or absence of
shock symptom, the therapeutic application of SMS could significantly reduce mortal-
ity caused by the acute myocardial infarction (Zhang et al. 1984). A study from the
No.1 Affiliated Hospital of Zhongshan Medical University showed that when SMS
was used for treating 35 cases of myocardial infarction, only one patient died and two
patients had recurrent infarction in a three-year post-treatment surveillance. It has been
reported that when treating elder patients suffering from acute myocardial infarction
with SMS in concomitant with a western drug, the effective rate was 93.8 per cent,
which was significantly higher than that afforded by the western drug alone per se
(82.0 per cent) (Hua and Qi 1996). While the mortality rate of SMS-treated patients
was 6.2 per cent, it was 18.0 per cent in patients given the western drug per se (Hua
and Qi 1996). By using the Swan-Ganz catheter, the hemodynamic effect produced
by SMS injection liquid on patients with acute myocardial infarction was examined
in Xiyuan Hospital (Dong et al. 1984). The result indicated that the infusion of
15–30 ml of SMS (10 ml/min) into the right atrium could increase the stroke volume
5 min after infusion, with the peak value being attained after 10–15 min and main-
tained for another 35 min. On average the stroke volume was increased by 19.5 per
cent. Patients given SMS showed a flushed complexion, reduced sweating and warm-
ness of limbs (Dong et al. 1984). A study from Tianjin Nankai Hospital (1973) has
shown that when patients suffering from acute myocardial infarction associated with
shock were given a western drug treatment, 7 out of 13 patients died. When the
western medication was supplemented with SMS injection liquid or Si Ni Tang (a
decoction for treating Yang exhaustion), none of the 10 patients died. As reported by
Mo et al. (1997), SMS, Astragali, and urokinase were administered for thrombolytic
treatment of acute myocardial infarction. While there was no observable difference
in the incidence of coronary reopening, when compared with the urokinase treatment
group, SMS, when administered together with urokinase, could reduce the incidence
of post-thrombolysis chest pain, complications of myocardial infarction, and the level
of plasma angiotensin II, with the state of hypoxemia being improved (Mo et al. 1997).
It has also been reported that SMS injection liquid produced significant therapeutic
efficacy on the atrioventricular block associated with acute myocardial infarction (Zhu
and Qiao 1998).
Clinical studies 47
C. Effects on heart contractility, cardiac output, coronary flow and
heart function
Clinical manifestations of CHD like shortness of breath, lassitude and palpitation
are directly related with the heart function. The treatment with SMS injection liquid
could significantly ameliorate these symptoms (Fang et al. 1987). Experimental results
indicated that SMS could enhance heart contractility and left ventricular function.
In this regard, the component herbs in SMS, namely Ginseng and Schisandrae, were
found to produce positive inotropic action (Shi et al. 1981). Various Ginseng-related
preparations could increase the contractility of isolated frog hearts and intact hearts in
rabbits, cats, and dogs, with the effect being independent of atropine and the influence
of vagus nerves (Shi et al. 1981).
It is now believed that the mechanism involved in the positive inotropic actions of
SMS is related to its ability to suppress the Na+/K+ ATPase activity of cardiomyocytes,
with the mode of action being similar to that of inotropic saponins. As observed by
Qin et al. (1983), SMS injection liquid inhibited the Na+/K+ ATPase activity of rat
cardiomyocytes by 25.0 per cent, whereas an ionic fluid, containing equivalent amounts
of Na+, K+, Ca2+, and Mg2+ present in SMS, inhibited Na+/K+ ATPase activity by only
6.5 per cent. While the enhancement in cardiac output afforded by positive inotropic
drugs is usually associated with an increase in peripheral resistance, the positive inotropic
effect produced by SMS is accompanied by the reduction in peripheral vascular resistance
to a varying degree. Therefore, SMS can increase the flow-output, but not the pressure-
output, with a reduction in oxygen consumption. An electromagnetic flow-meter was
catheterized to the ascending branch of the left circumflex coronary artery in anesthetized
dogs, the coronary blood flow was found to increase following the intravenous infusion
of SMS injection liquid at a dose of 1 ml/kg (Zhang and Yang 1986). The increased
coronary flow was also associated with a concomitant enhancement in the peripheral
arterial flow (Zhang and Yang 1986). Zhou et al. (1997) used a doppler ultrasonic
detection technique and reported that in the absence of β-receptor blocker and calcium
antagonist, SMS injection liquid was able to improve the left ventricular diastolic
function. The result suggested that SMS injection fluid could be used for the treatment
of uncomplicated left ventricular diastolic dysfunction or both diastolic and systolic
dysfunction. The therapeutic action of SMS is therefore different from that of conven-
tional positive inotropic drugs (Zhou et al. 1997).
Clinical studies have demonstrated that SMS treatment could reduce the incidence
of angina pectoris and the extent of myocardial damage caused by acute myocardial
infarction, and facilitate the repair of damaged myocardial tissue (Wang et al. 1997).
SMS treatment could also reduce the incidence of complications and mortality
caused by acute myocardial infarction. Because of the faster onset of therapeutic action
with an injection of SMS when compared to an oral treatment, patients under crit-
ical conditions with life-threatening symptoms are usually administered with SMS
injection liquid (every 10 ml of SMS injection liquid is comprised of Radix Ginseng
(1 g), Radix Ophiopogonis (3 g) and Fructus Schisandrae (1.5 g)). The Shanghai City
Clinical Cooperative team for SMS Injection Liquid, as led by the Department of
Cardiology in Xinhua Hospital (1999), has reported the clinical effect of SMS injec-
tion liquid on 248 patients suffering angina pectoris. All patients selected for the
study fulfilled the diagnostic criteria of the World Health Organization (WHO)
for coronary heart disease-derived angina pectoris published in 1979. SMS injection
liquid was given by intravenous infusion at a daily dose of 80 ml, consecutively for
fourteen days, while the control group was given Danseng (Radix Salviae Miltiorrhizae)
injection liquid at a daily dosage of 16 ml. With reference to the evaluation criteria
established by the National Conference on the Integration of Chinese and Western
Medicine for the Prevention and Treatment of Coronary Heart Disease, Angina
Pectoris and Arrhythmia in 1979, the respective treatment would be regarded as
effective if the symptom of angina pectoris was reduced by more than one grade
and the use of nitroglycerin was not required or reduced by more than 50 per cent
in dosage (Department of Cardiology, Xinhua Hospital 1999). In addition, if the
ST segment was increased by more than 0.05mV after the drug treatment under rest-
ing conditions, the electrocardiogram would be regarded as being improved. The
treatment would be regarded as ineffective if the symptomatic improvement was not
obvious or stable. Results indicated that SMS injection liquid was superior to Danseng
injection liquid in therapeutic efficacy on relieving the shortness of breath, myocardial
ischemia-induced chest pain (chest distress) and palpitation (cardiac terror), with the
improvement in symptoms being observed on the third to fifth day after the drug
treatment. As assessed by doppler ultrasonic measurement, the cardiac output was
found to be increased, and the peripheral vascular resistance decreased, both were
indicative of improved heart function. The effective rate, as assessed by electro-
cardiogram, was 71.2 per cent for the SMS group, which was better than that of the
Danseng group (60.0 per cent). Meanwhile, SMS treatment could produce a similar
action to Danseng in decreasing the blood viscosity. The Cooperative Team for
Emergent Treatment of Chest bi-syndrome Under the State Administration of Tradi-
tional Chinese Medicine, China (SATCM 1995) conducted a clinical investigation
in which 219 patients suffering from angina pectoris associated with deficiency of
both Qi and Yin were treated with SMS injection liquid by intravenous infusion at
a daily dose of 40 ml. Results indicated that the effective rate in relieving pain was
95.0 per cent, and the effective rate in ameliorating other symptoms was 93.6 per
cent. The effective rate in stopping and reducing the use of nitroglyceride drugs
was 61.5 per cent, and that in improving the electrocardiogram under ischemia was
68.5 per cent. The myocardial oxygen consumption was also significantly reduced. SMS
injection liquid tended to produce a better therapeutic efficacy on unstable angina
pectoris (Sun and Wang 1998). By differentiation of signs and symptoms, the therapeutic
efficacy afforded by SMS injection liquid on angina pectoris of deficiency of both Qi
and Yin type was superior to that of the heart-blood stasis type. It has been reported
that the total effective rate of SMS injection liquid was 92.5 and 78 per cent, respec-
tively, for unstable angina pectoris (Sun and Wang 1998) and angina pectoris (Wang
et al. 1997) unresponsive to diltiazem and nitroglycerin treatment. The effective
rate in improving the electrocardiogram for asymptomatic myocardial ischemia was
93.8 per cent (Su 1998).
D. Effect on thrombosis and blood clotting function

CHD is usually associated with an enhancement in a series of blood adhesive factors.
On the incidence of angina pectoris or at the early stage of myocardial infarction,
a variety of cells like vascular endothelial cells, blood platelets, and leukocytes will
release a large amount of vasoactive substances including angiotensin II, thromboxane,
and platelet activating factors (PAF). Up until now, PAF is the strongest known
Clinical studies 49
stimulant for the platelet activation and aggregation, which can facilitate thrombosis
by increasing the blood viscosity and reducing the blood flow.
Experimental studies from the Shanxi Provincial Academy of Traditional Chinese
Medicine demonstrated that SMS injection liquid could inhibit the process of throm-
bosis in rabbits, with the time of thrombus formation being prolonged and the mass
of the thrombus being reduced (Xu et al. 1986). SMS injection liquid also significantly
prolonged the prothrombin time and time of plasma prothrombin consumption, as
well as reducing the fibrinogen content of the thrombus. The results suggest that SMS
injection liquid could ameliorate the high tendency for blood coagulation. Lu et al.
(1998) have examined the changes in blood viscosity in 53 cases of CHD before and
after the SMS injection liquid treatment (80 ml/day). The results indicated that SMS
treatment significantly reduced the blood viscosity (including the upper and lower
shear limit of the whole blood, plasma viscosity and red blood cell sedimentation),
which was associated with a reduction in the adhesion, as well as the 1-min, 5-min,
and maximal aggregation of blood platelets. The action mechanism may be related to
the ability of Shengmai injections to enhance the synthesis of prostacyclin, inhibit the
production of thromboxane, and selectively antagonize the PAF.
E. Modulatory effect on blood pressure and improvement in microcirculation

SMS can produce a biphasic modulatory action on blood pressure, with the systolic
blood pressure being slowly increased under the condition of hypotension and being
slightly decreased under the condition of hypertension, while the normal blood pres-
sure is not affected (Pathophysiology Research Group, Beijing Medical University
1978). It has been reported by Li (1978) that SMS injection liquid was used for
treating six patients of acute myocardial infarction accompanied by cardiogenic shock.
Four of the patients, who failed in the treatment with vasopressive amine, were switched
to the treatment with SMS injection liquid, while the other 2 patients were only given
the SMS treatment throughout the study. SMS treatment was found to be efficacious,
with blood pressure of all treated patients being increased by 20 mmHg on average.
The onset of pressive effect being observed 15–20 min after intravenous infusion,
which was different from instantaneous action produced by vasopressive amine. In
addition, the elevated blood pressure in SMS-treated patients could be sustained for at
least 7 hours, indicating that the SMS has a modulatory effect produced by SMS treat-
ment on vascular tone. However, the mechanism involved remains to be elucidated
(Li 1978).
F. Others
It has been reported that SMS could increase the cholesterol level of high-density
lipoprotein, but did not affect the level of total cholesterol and triglyceride in pati-
ents suffering from CHD. In addition, SMS could modulate the level of endogenous
glucocorticoid hormone. It has also been reported that SMS was capable of signific-
antly reducing the level of ß-receptor-induced cAMP level in the patients with CHD.
Plasma levels of anti-coagulase and PGF1α were increased, while the concentration
of thromboxane ß2 was decreased in CHD patients treated with SMS (Wang et al.
1999). SMS treatment could also increase the rate of myocardial DNA synthesis
(Liu et al. 1978).
V. Conclusions
From experimental studies to clinical applications for the prevention and therapy of
CHD, the results of SMS treatment have been encouraging. Given the absence of or
little side effect produced by naturally-occurring herbal formula, the clinical application
of SMS for the treatment of cardiovascular diseases, particularly the prevention and treat-
ment of CHD, is very promising. As TCM is gaining attention worldwide, experimental
and clinical investigations on SMS and its related preparations will proceed further
in the future. The future trend in research and development of SMS should be focused
on the following aspects: 1) the further elucidation of dose-dependent relationship;
2) the extraction and the subsequent recombination of major active components from
the herbs and 3) in-depth investigation on the action mechanism of SMS in cardiovascu-
lar system from cellular and biochemical level to molecular and gene level.
CARDIAC ARRHYTHMIA
Cardiac arrhythmia (also called arrhythmia), an abnormal rhythm of heart activities,

can occur in patients suffering from various kinds of organic heart diseases and other
diseases. The clinical significance of arrhythmia is determined by the etiology, dura-
tion and hemodynamic changes associated with the arrhythmia. Severe arrhythmia
can cause the decrease in cardiac output, insufficient organ perfusion and even death.
Clinical manifestations include palpitation, chest-pain, chest distress (the feeling of
oppression over the chest), shortness of breath, syncope and sudden death.
Arrhythmia is classified into two main types, namely tachycardia and bradycardia. The
more commonly occurring tachycardia is associated with incidences of atrial fibrillation,
atrial flutter, supraventricular paroxysmal tachycardia, and ventricular tachycardia, while
sick sinus syndrome and interruption could be found in the cases of bradycardia.
The earliest clinical record of arrhythmia in traditional Chinese medicine can be dated
back to the period of the Han Dynasty. Dr. Zhang Zhong-jing had described the
symptoms of and therapy for the conditions of irregular pulse in ‘Treatise on Exogenous
Febrile Diseases’. He also reported that the slow and irregular pulse and palpitation
could be treated with Glycyrrhizae decoction. After the Tsui and Tang Dynasty, reports
on pulse studies gradually emerged. The ‘Pinhu’s Sphygmology’ by Li Shi-zhen had
described the pulse conditions of arrhythmia in further detail, like slow pulse, irregular
pulse, and abrupt pulse. Studies from ancient physicians in TCM have accumulated a
huge volume of information for the understanding and clinical treatment of arrhythmia.
SMS is a TCM formula prescribed for benefiting the vital energy and recuperating
the pulse. Nearly one thousand years ago, SMS had already been used for the treatment
of arrhythmia. Not until the recent decades, the therapeutic action of SMS has further
been confirmed by clinical investigations. The therapeutic effect of SMS on tachycardia
and bradycardia will be described in the following sections.
I. Treatment of tachycardia with SMS
A. Atrial fibrillation
Atrial fibrillation is a manifestation of irregular contraction of atrial cardiac muscles,
with the frequency being 400–600 beats/min. Atrial fibrillation is usually associated
Clinical studies 51
with common organic heart diseases like coronary heart disease and rheumatic heart
disease. In addition, it can also be found in patients suffering from hyperthyroidism.
Idiopathic atrial fibrillation can be found in 5–6 per cent of patients who have no
history of any heart diseases.
Symptoms of atrial fibrillation, including palpitation, shortness of breath and con-
tractile failure, are related to the change in heart function and ventricular rate. The
detachment of a thrombus from the wall of the vessel lumen can lead to myocardial
infarction.
B. Treatment of atrial fibrillation with SMS

According to the theory of TCM, the pathogenesis of atrial fibrillation caused by
rheumatic heart diseases usually involves the deficiency of both heart-Qi (vital energy)
and heart-Yin, and the inability to disperse of water and dampness. The respective therapy
should therefore be aimed at replenishing the vital energy and nourishing the Yin for
rectifying the abnormal body function (i.e. cause of the disease) as well as inducing
diuresis for symptomatic relief. As such, SMS injection liquid (80 ml, supplemented
with 500 ml of physiological liquid adjuvant) was given by an intravenous drip once
a day for 2 weeks (Zhu et al. 1997). Meanwhile, digitalis and diuretics were pre-
scribed for reducing cardiac workload and improving heart contractile function. The
pathogenesis of atrial fibrillation caused by coronary heart disease usually involves the
deficiency of heart-Qi and the blockage of vessels and channels (meridian). The correspond-
ing treatment should also be aimed at replenishing the Qi (for removing the cause of
the disease) and opening the vessels and channels (for relieving the symptoms). SMS
could be used for benefiting the Qi and at the same time, vasodilators and anticoagulants
were prescribed.
The therapeutic strategy for atrial fibrillation should integrate the Differentiation
of Signs and Symptoms (TCM) and clinical diagnosis (modern medicine). The kind of
treatment would primarily be determined by the course of the disease and the cardiac
rate. Therapeutic interventions from modern medicine should be adopted for the
rapid control of over-driven atrial fibrillation associated with serious hemodynamic
disorders. When treating atrial fibrillation without obvious hemodynamic disorders,
the adoption of digitalis based treatment together with SMS usually produced good
therapeutic outcome.
C. Premature beat
Premature beat is advanced heart beating caused by the earlier impulse generated from
ectopic focus. This focus can be of atrial, junctional, and ventricular types according to
its location. Atrial ectopic focus is second to the more commonly occurring ventricular
focus. Premature beat, which can be found in normal individuals, is associated with
psychasthenia, tiredness, cigarette smoking, and alcoholic intake. It can also be caused by
pathological changes in the mitral valve, myocarditis, cardiomyopathy, cardiopulmonary
diseases and congenital heart diseases. Ventricular premature beat can also be found in
normal individuals; however, it is more likely associated with organic heart diseases
like coronary heart disease, myocarditis, cardiomyopathy, and mitral valve prolapse.
TCM regards premature beat as a result of emotional upset, stagnation of liver-Qi,
deficiency of heart-Qi and exhaustion of heart-Yin. The insufficient heart-Yang results
in water retention and the heart-blood stasis associated with severe palpitation.
While single or occasional incidences of premature beat would not produce any
symptoms, some of the affected individuals may have discontinuous pacing or inter-
mittent feeling of strong and forceful beating. Frequent or persistent premature beat
can reduce cardiac output and the blood perfusion of major organs, causing palpitation,
lassitude, angina pectoris or breathlessness.
D. Treatment of premature beat with SMS

Given that the integration of TCM and modern medical treatment can produce a more
effective preventive and therapeutic outcome, the therapeutic strategy for premature
beat should be based on both the Differentiation of Signs and Symptoms (TCM) and clin-
ical diagnosis (modern medicine). As described by Wang et al. (1997), SMS injection
liquid was used for treating 46 cases of coronary heart disease and hypertension
associated with positive ventricular late potential (VLP) by intravenous infusion at a
single daily dose of 40 ml, for 15 consecutive days. The results indicated that the rate
of negative VLP was 82.6 per cent, with the ventricular and atrial premature beat
disappearing in all VLP negative individuals. As reported by Chen and Wu (1996),
the integration of TCM and modern medicine was adopted in treating twenty-two
cases of refractory ventricular arrhythmia. It was found that 82 per cent of the treated
cases were effective, particularly in arrhythmia caused by early coronary heart disease,
viral myocarditis, and other unknown causes. The blood pressure and cardiac rate did
not show any significant change before and after the drug treatment. The effect of a
supplemented SMS preparation on patients suffering from coronary heart disease and
showing positive VLP has been reported by Zeng (1996). Thirty-two cases of positive
VLP were randomly divided into two groups, which were given supplemented SMS
preparation and ‘heart painkiller’, respectively. The patients of the two groups did
not have any significant differences in ages, sex, and the course of sickness. Results
from the study indicated that the rate of negative VLP afforded by the supplemented
SMS preparation treatment was 75.0 per cent, while that afforded by the ‘heart
painkiller’ was 9.38 per cent, with the group difference being statistically significant
( p < 0.01). The author believed that the supplemented SMS preparation could signific-
antly protect against myocardial ischemia/reperfusion-induced injury and improve the
metabolism of cardiomyocytes. It can also nullify the unsynchronized depolarization
and delay the conduction of bioelectricity in cardiomyocytes. All of these actions
produced by the treatment of supplemented SMS preparation could eventually lead
to the conversion of coronary heart disease-associated VLP from positive to negative
sign. The use of a supplemented SMS preparation is also effective for the prevention
of lethal arrhythmia. By the Differentiation of Signs and Symptoms in TCM, arrhythmia
can be classified into three types, namely deficiency of Qi and Yin, stagnation of
Qi and blood stasis, and stagnation of phlegm-dampness. Patients of these three types
of arrhythmia were treated with corresponding herbal decoction including SMS and
performed Qigong-respiratory exercise. Significant therapeutic efficacy of these treat-
ment regimens was found, with total effective rate being 86 per cent. The result
indicated that the present treatment regimen comprising herbal decoction and Qigong
exercise was an effective method for treating arrhythmia. As reported by Zhou (1996),
twelve cases of frequent premature beat, with the course of the disease being longer
than three months and failed in anti-arrhythmic drug treatments, were treated with
amiodarone together with a high dose of oryzanol and Astragali supplemented SMS
Clinical studies 53
oral liquid. Results indicated that the effective rate was 83.3 per cent, with ten and
two cases being cured and failed, respectively. The author suggested that these drugs
may exert their therapeutic effect indirectly through metabolic regulation or pro-
tection against ischemia. Through the intermediacy of the central nervous system or
peripheral nervous system, the favorable changes in hemodynamics and/or metabolism
can produce the therapeutic effect. In this case, the three drugs, namely amiodarone,
Astragali and SMS, may act synergistically in producing the therapeutic effect,
which cannot be afforded by the individual use of the drugs. Du et al. (1998) have
investigated the effect of SMS injection liquid on the arrhythmia caused by the com-
plication of hyperthyroidism. Forty-three cases of hyperthyroidism with frequent atrial
premature beat and ventricular premature beat were divided into treatment group and
control group. Treatment group (22 cases) was given 10 mg of methimazole orally,
three times per day, together with SMS injection liquid (20 ml) (in 500 ml physiological
liquid adjuvant containing 5 per cent of glucose) via intravenous infusion, once per
day. The control group (21 cases) was only given methimazole at the same dosage
regimen used in the treatment group. Results indicated that after two weeks of drug
treatment, the effective rate in protecting against arrhythmia was 72.7 and 47.8 per
cent in treatment group and control group, respectively, with the difference between
the two groups being statistically significant ( p < 0.05). The results suggested that
SMS injection liquid could be used for treating arrhythmia in patients suffering from
hyperthyroidism.
II. Treatment of bradycardia with SMS

Bradycardia, a heart rate slower than 60 beats per minute, is usually associated with
sinus bradycardia, sick sinus syndrome, sinus arrest, sinoatrial block, and atrioventricu-
lar block. Its incidence is likely related to pathological changes in the myocardium,
increased vagal influence on a normal pacemaker, hyperkalemia, and side effects of
certain drugs.
The descriptions of bradycardia in TCM include palpitation, severe palpitation, chest
bi-syndrome (pain), dizziness, Jue-syndrome and the slow and irregular pulse conditions.
The disorder was believed to be caused by the deficiency of Yang-Qi and the stasis of
heart-blood.
A. Clinical manifestations
Mild cases of bradycardia produce no symptoms, or only the feeling of oppression over
the chest and palpitation. But severe cases are associated with symptoms such as
dizziness, shortness of breath, lassitude, syncope, and Adams-Stokes syndrome.
B. SMS treatment
When the installation of an artificial pacemaker in patients suffering from sick
sinus syndrome is not feasible, the treatment with SMS plays a significant role in the
clinical management of bradycardia. The administration of a combination of SMS (for
replenishing the Qi and nourishing the Yin) and a herbal formula (Bao Yuan Tang,
for preserving the primordial-Qi) was found to be more effective than SMS alone, in
enhancing cardiac rate and improving heart function.
As described by Zhu et al. (1995), the clinical efficacy of SMS (when administered
together with nicotinamide) for treating senile bradycardia was examined. One hundred
and sixty eight cases were given SMS orally and nicotinamide by intravenous infusion.
Results indicated that the total effective rate was 99.0, 93.8 and 87.5 per cent, in
treating sinus bradycardia, sick sinus syndrome and heart block respectively, indicat-
ing that the combined use of SMS with nicotinamide could produce synergistic action
in shortening the course of disease and enhancing the therapeutic efficacy.
PRIMARY CARDIOMYOPATHY
Primary cardiomyopathy, a disease state originated from the myocardium, is clinically

classified into idiopathic cardiomyopathy and specific cardiomyopathy. Idiopathic cardio-
myopathy is the cardiomyopathy associated with impaired heart functions, and can be
further classified into dilated cardiomyopathy, hypertrophic cardiomyopathy, restrict-
ive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Specific
cardiomyopathy is associated with specific heart diseases or other systemic diseases,
which include ischemic cardiomyopathy, valvular cardiomyopathy and hypertensive
cardiomyopathy, etc.
I. Treatment of dilated cardiomyopathy-derived heart failure

by Shengmai San
Since there is no curative treatment for dilated cardiomyopathy, symptomatic treatment
is mainly used at the present time. While the majority of cases of dilated cardiomyopathy
were not diagnosed until the initial strike of heart failure, the treatment regimen is
generally similar to that of treating heart failure, with the aims being to 1) relieve
symptoms and thereby improve the quality of living; and 2) to protect the myocardium
in order to prolong the survival time. For mild cases of heart failure, the treatment is
mainly focused on protecting the myocardium, while the amelioration of symptoms
and protection of the myocardium are more critically needed in severe cases of heart
failure. If all these treatments remain ineffective, cardiac transplantation would be
required.
A. Improvement in left ventricular functions and exercise-endurance

Dilated cardiomyopathy is the chronic deterioration of pump functions caused by
diffused myocardial damage associated with systolic or diastolic disorder of the left
ventricle or bilateral ventricles. Its causes could be idiopathic, familial or hereditary,
viral and/or immunological, due to alcoholic or toxic factors, as well as secondary to
known cardiovascular conditions. In clinical situations, there has not been a single
ideal drug for the disease.
Patients with myocardiopathy given SMS treatment showed significant improvement
in left ventricular systolic functions, as assessed by M-type echocardiogram and systolic
time intervals. Jiang et al. (1988) have reported that oral SMS treatment could reduce
the internal circumference of the left ventricle and significantly increase the ejection
volume indices (EF and CO), suggesting that SMS could improve the deteriorated left
ventricular systolic functions. Since the improvement in ventricular functions was not
Clinical studies 55
associated with changes in cardiac rate and blood pressure, it was postulated that the
effect was mediated by an enhancement in myocardial contractility. In this connection,
SMS treatment was shown to improve the circumferential fiber-shortening rate, which
could more directly reflect the myocardial contractile function. This observation further
indicated that SMS could enhance the myocardial contractility under conditions of
cardiomyopathy.
B. Effect of SMS on exercise-eudurance and its implications

It is well accepted that the efficacy of drugs used for treating chronic heart malfunction
can be most sensitively assessed by an endurance study using physical exercise. While
one of the targets in the management of cardiomyopathy is to enhance the ‘quality of
living’ of the patients, an endurance study provides a convenient and reproducible means
of assessing the effectiveness of treatments. Studies by Jiang et al. (1988) demonstrated
that cardiomyopathic patients receiving SMS treatment showed enhanced endurance to
physical exercise, without an accompanying increase in oxygen consumption (indicated
indirectly by multiplying the heart rate with the systolic pressure). These observations
suggested that SMS treatment could improve cardiac mobility without increasing the
myocardial oxygen consumption in the patients of cardiomyopathy. A huge amount of
reports have indicated that SMS and its herbal component, Ginseng, could enhance the
tolerance of the myocardium towards anoxic conditions and protect the myocardial
ultrastructure from damage, thereby enhancing the endurance to physical exercise. All
in all, SMS may produce multiple effects for the improvement of endurance under
conditions of cardiomyopathy.
C. Improvement in the hemodynamic markers by SMS injection liquid under

conditions of heart failure induced by dilated cardiomyopathy
Dilated cardiomyopathy is a common form of cardiomyopathy manifested by bilateral
ventricular expansion, reduction in ventricular contractility and cardiac output, and
increased ventricular end-diastolic pressure. Patients usually die of heart failure,
arrhythmia or sudden death. No effective drug is available for the treatment of dilated
cardiomyopathy. Even with the use of inotropic saponin (cardiac glycosides), diuretics,
and vasodilator, their prognosis is still unfavorable. Recent studies have indicated that
SMS, which can improve the left ventricular function, has been prescribed for coronary
heart disease, acute myocardial infarction and toxic shock.
Zhang et al. (1990) have studied the hemodynamic effect of Shengmai injection
liquid on the patients of dilated cardiomyopathy with heart failure (22 cases) by
recording their bifunctional echocardiograms. Results showed that after the intravenous
injection of SMS, the stroke volume (SV), cardiac output (CO), cardiac index (CI),
ejection fraction (EF), endocardial fractional shortening (∆D per cent), and thicken-
ing rate of the ventricular wall (∆T per cent) were significantly increased, while the
systemic vascular resistance (SVR) was significantly decreased. The heart rate, average
arterial pressure, E-point septal separation (EPSS), and the end-systolic stress (ESS)
did not show any significant changes. The effects of SMS on the pathophysiology of
the dilated cardiomyopathy were manifested by the expansion of bilateral ventricle,
attenuation of ventricular contractility, reduction in cardiac output, and the enhance-
ment in ventricular end-diastolic pressure (Zhang et al. 1990).
Patients exhibited a declined pump function even in the asymptomatic compensation
period, but the deterioration of pump functional markers becomes significant as symp-
toms appear. Clinical observation indicated that the stroke volume, cardiac output,
cardiac index, ejection fraction, endocardial fractional shortening, and thickening rate
of ventricular wall were significantly lowered in patients of dilated cardiomyopathy.
After intravenous infusion of SMS preparation, various parameters that reflect ventricu-
lar contractility were significantly elevated, suggesting the improvement in cardiac
pump function. Among these, elevations in the shortening rate of the left ventricular
axis (∆D per cent) and thickening rate of the ventricular wall (∆T per cent) were
particularly significant. The myocardial fiber during contraction of left ventricle was
shortened by 60 per cent, the shortening percentage change was closely correlated
with ejection fraction, and is usually greater than 30 per cent. Ventricular wall thick-
ening during the diastolic period is an important manifestation of myocardial con-
tractile functions. Echocardiography examinations demonstrated that the ventricular
wall mobility of the patients was generally lowered, with the thickening rate of the
ventricular wall (∆T per cent) being significantly decreased. After the drug treatment,
contractility of the left posterior ventricular wall and the intraventricular septum
was enhanced, as indicated by the significant increases in shortening rate of the right
ventricular axis (∆D per cent) and thickening rate of the ventricular wall (∆T per cent)
(Zhang et al. 1990). These observations have suggested that SMS injection liquid may
enhance myocardial contractility and cardiac output, which are consistent with its
known pharmacological actions.
E-point septal separation (EPSS) is a sensitive marker for assessing right ventricular
function. When heart function is impaired, early diastolic bicuspid blood flow and the
extent of opening of bicuspid anterior lobe would be reduced. On the other hand, the
EPSS value would increase, usually not more than 5–8 mm, and show a negative and
positive correlation with the ejection fraction and end-diastolic pressure, respectively.
Patients of dilated cardiomyopathy were found to have significantly elevated EPSS
values. After SMS injection, the cardiac output was significantly enhanced while the
EPSS did not show any significant changes. The failure of SMS to change EPSS may be
due to the relatively weak heart function in the patients, leading to the small expansion
in left ventricular internal circumference.
D. Effect of SMS injection on the after-load of dilated cardiomyopathy

During the course of heart failure in dilated cardiomyopathy, the left ventricular after-
load would increase as a result of decreased cardiac output and autonomic vasoconstric-
tion of the systemic circulation, resulting in a further decrease in cardiac output. The
increase in after-load would usually cause myocardial hypertrophy. However, under
the condition of dilated cardiomyopathy, the increase in myocardial weight was not
accompanied with thickening of the ventricular wall, despite an overloading of the
ventricle. The ratio of ventricular wall thickness and internal circumference of the
heart chambers tends to be normal or decreased, without causing compensatory cardiac
hypertrophy.
Studies indicated that during the compensatory stage of heart function, patients with
dilated cardiomyopathy were found to have reduced myocardial contractility, lowered
ejection fractions, but a normal peripheral resistance in the systemic circulation. When
the heart functions further deteriorated with incidence of apparent heart failure, EF
Clinical studies 57
would reduce to less than 40 per cent, with a concomitant increase in peripheral
vascular resistance. This abnormal increase in the after-load, termed ‘after-load dismatch’,
can significantly impair the contractile function of the heart, and it is one of the import-
ant factors for the induction of heart failure, in which the use of vasodilators can
improve the heart functions.
Studies with dogs indicated that injection of Ginseng saponins could reduce the
vascular resistance in vertebral and vastus arteries. In patients, treatment with Shengmai
injection liquid could lower the PVR and the left ventricular after-load, thereby elevat-
ing the CO, CI, and EF. These findings point to a direct vasodilating action of SMS on
resistant vessels. Given its ability in enhancing myocardial contractility and dilating
blood vessels, SMS injection liquid may be a candidate for the effective treatment of
heart failure in dilated cardiomyopathy.
II. Combination of Chinese medicine and western medicine treatment

for the intractable heart failure of the dilated cardiomyopathy
A. Combined use of SMS and diuretics

Dilated cardiomyopathy is usually associated with intractable heart failure, particularly
an uncontrollable heart rate. While digitalis treatment can easily produce poisoning
effects, treatment with high dosages of β-receptor blockers may have the side effects
of inducing or exaggerating heart failure, so these drugs cannot effectively improve
the heart functions. The use of SMS in adjunct with western drug treatments can
avoid these shortcomings of using a western drug alone, and result in good therapeutic
efficacy (Yuan and Zheng 1997).
By the Differentiation of Signs and Symptoms in traditional Chinese medicine, dilated
cardiomyopathy belongs to mild or severe ‘palpitation’, manifested by deficiencies of
the Qi (vital energy) and Yin, and retention of dampness and anxiety (Zhang H. 1997).
These symptoms should therefore be treated by invigorating the Qi and nourishing
the Yin, eliminating dampness and diuresis, as well as tranquilizing the mind. Modern
pharmacological studies have shown that SMS could improve heart function and enhance
the myocardial contractility, with its positive ionotropic action being similar to that
of lanatoside. SMS can also enhance the oxygen inhaling and carrying capacity of the
body, thereby invigorating the Qi.
The combined use of SMS and diuretics can reduce cardiac workload, enhance the
myocardial contractility, relieve heart failure, and improve heart functions. Yuan and
Zheng (1997) reported the study in 100 cases of intractable heart failure of dilated
cardiomyopathy with a co-treatment of SMS and diuretics. Apparent therapeutic efficacy
was found, as indicated by the significant improvement in various heart functional
markers, including cardiac output (CO), stroke volume (SV), cardiac index (CI), ejection
fraction (EF), and total peripheral resistance (TPR). These observations indicated that
the combined use of SMS and diuretics was superior to the conventional single drug
treatment for treating the intractable heart failure of dilated cardiomyopathy.
B. Combined use of SMS and dopamine

Lu et al. (1997) described the use of SMS injection liquid in combination with dopamine
in 34 cases of heart failure associated with dilated cardiomyopathy. SMS treatment had
a significant effect in 15 cases, and was effective in another 16 cases, with an overall
effective rate of 91.2 per cent.
In addition to its anti-arrhythmic effects, SMS injection could improve the heart
functions by fundamental means, such as enhancing the myocardial tissue metabolism
and facilitating the restoration of deteriorated myocardial functions, indicating that
SMS is an effective drug for heart failure.
Dopamine is a non-glycoside inotropic drug, and is the precursor for the biosynthesis
of noradrenaline and adrenaline. It can activate the α- and β-adrenergic receptors, as
well as the dopamine receptors. It has been reported that the use of an intravenous
infusion of dopamine in treating level IV heart dysfunction of different pathogenic
origins, except in the case of wind epigastralgia, produced a satisfactory therapeutic
effect. At a normal dosage, dopamine could enhance myocardial contractility and
cardiac output, induce arterial/venous vasodilation, and improve microcirculation. It
could also enhance renal blood flow and glomerular filtration rate as well as facilitate
urination and sodium excretion, thereby reducing the workload of the heart. Dopamine
could also reduce the vascular resistance of pulmonary circulation, and increase
the blood supply to the myocardium by stimulating coronary vasorelaxation, thereby
producing beneficial hemodynamic changes. At higher dosages, it could significantly
increase both systolic pressure and arterial pressure. While the short-term use of
dopamine is highly effective, drug tolerance develops as the body becomes desensitized
after prolonged use, and as a result the efficacy of the drug declines. On the other
hand, SMS injection liquid produces the actions of invigorating the Qi, nourishing
the Yin, strengthening the pulse, replenishing exhaustion, inducing vasodilation, and
enhancing coronary flow. The co-administration of SMS and dopamine may suggest
an effective treatment for heart failure in dilated cardiomyopathy by virtue of their
synergistic action that can shorten the course of treatment and minimize the incidence
of drug tolerance.
C. Combined use of SMS and dobutamine

Tan (1997) reported the use of SMS injection in combination with dobutamine for
treating heart failure in dilated cardiomyopathy (35 cases) and observed good therapeutic
efficacy. The significantly effective rate for clinical symptoms/signs and the total effective
rate were found to be 60 and 90 per cent, respectively. The heart-chest ratio, the left
ventricular end-diastolic internal circumference and the incidence of arrhythmia were
significantly reduced.
The theory of traditional Chinese medicine holds that somatic asthenia is critical
in the pathogenesis of dilated cardiomyopathy, particularly under the condition of
Qi-deficiency. The Qi is the vital energy for the body. Deficiency in primordial-Qi could
impair visceral functions, causing metabolic inadequacy associated with Qi- and Yin-
deficiencies, and malnourishment of the heart. Deficiency of the Qi could impair blood
circulation, manifested as a weak pulse, blood stasis and palpitations. Cardiomyopathy
is usually asymptomatic, incurable and recursive in nature, causing damage to the spleen
and stomach eventually. While the deficiency of the spleen would hinder the transforma-
tion of body fluid, deficiency of the kidney would lead to the accumulation of dampness,
causing edema and retention of fluid in the lung, shortness of breath with coughing,
and disturbance in renal reabsorption and dyspnea when prostrate.
Clinical studies 59
Ginseng is the ‘Monarch’ herb (the principal herb) in the formulation of SMS. It
produces actions of invigorating the lung, benefiting the Qi through the channels to
the lung, spleen and heart, invigorating the primordial-Qi, invigorating the spleen and
nourishing the lung, promoting body fluid production and tranquilizing the mind.
Ophiopogoniae, being the ‘Minister’ herb in SMS, exerts its actions through the channels
to the lung, stomach and heart, nourishes the Yin, benefits the stomach, moistens the
lung, and dissipates heat in the heart. Schisandrae serves as the ‘Assistant’ herb that acts
through the channels to the lung, heart, and kidney in benefiting the Qi and promot-
ing body fluid production, invigorating the kidney and nourishing the heart, restoring
the astringent functions, retaining the lung-Qi, and preventing excessive perspira-
tion. The invigorating, astringent and dissipating actions of Ginseng, Schisandrae
and Ophiopogoniae, respectively, act synergistically in SMS to supplement the Qi and
nourish the Yin, to promote body fluid production and prevent thirst, to retain the
Yin and restore the astringent functions, to prevent collapse by enriching the Qi,
and recuperating normal pulse and body fluid content. For the treatment of dilated
cardiomyopathy, SMS can restore organ functions and strengthen the healthy Qi.
Pharmacological studies indicate that SMS is capable of 1) producing positive inotropic
actions; 2) enhancing the coronary flow; 3) improving myocardial metabolism; 4)
modulating the blood pressure; 5) improving the microcirculation; 6) inhibiting the
process of thrombosis; 7) reducing oxygen consumption of myocardium; and 8) modu-
lating the level of endogenous glucocorticoid hormone. Therefore, SMS treatment could
enhance the myocardial contractility and improve the heart functions of patients with
cardiomyopathy.
Dobutamine can activate the ß1-, ß2- and α-adrenergic receptors. Since its stimu-
latory action on the ß1-receptors is much stronger than that on the ß2-receptors, it
can increase the myocardial contractility and cardiac output. Meanwhile, its stimulation
on the ß2-receptors results in the dilation of the peripheral vessels, thereby lowering
the peripheral vascular resistance and the pulmonary wedge pressure. Therefore, dobuta-
mine can produce definite therapeutic effects on intractable heart failure, provided that
it is not administered at high dosages. Worsening of heart functions, such as elev-
ated heart rate and increased peripheral vascular resistance, has been reported when
dobutamine was given at doses exceeding 10 µg/kg/min. For the treatment of dilated
cardiomyopathy, the dosage of dobutamine should be carefully controlled. A low dose
of dobutamine (5 µg/kg/min) co-administered with SMS injection liquid has been
reported to produce apparent efficacy.
On the other hand, dobutamine has been reported to lower the levels of potassium
and magnesium in blood, thereby disturbing the electrolyte balance and exaggerat-
ing ventricular arrhythmia. In contrast, when dobutamine was co-administered with
SMS injection liquid, the occurrence of these side effects has been significantly
reduced. It is obvious that anti-arrhythmic action of SMS is favorable to the treatment
of dilated cardiomyopathy, which is usually associated with arrhythmia. In fact, the
co-administration of SMS and dobutamine could significantly reduce the occurrence of
ventricular arrhythmia and reverse cardiac enlargement, as assessed by the heart-chest
ratio and the end-diastolic internal circumference of the left ventricle. The restora-
tion of heart functions by co-administering SMS and dobutamine may implicate their
synergistic action in reducing heart workload, improving myocardial metabolism, and
reducing left ventricular end-diastolic pressure.
III. Treatment of arrhythmia of dilated cardiomyopathy by SMS
injection liquid
The incidence of frequent ventricular premature beat and discontinuous ventricular
tachycardia associated with dilated cardiomyopathy are 70–95 and 40–80 per cent,
respectively. The relationship of tachycardia with sudden death has yet to be deter-
mined. Although asymptomatic discontinuous ventricular tachycardia is usually observed
in the ambulatory electrocardiogram, the use of anti-arrhythmic drugs for the treatment
of dilated cadiomyopathy remains questionable.
Dilated cardiomyopathy is usually associated with various types of arrhythmia, and
its treatment regimen is usually subjected to different limitations. Zhang et al. (1997)
studied the effect of SMS injection liquid in 40 cases of dilated cardiomyopathy com-
plicated with arrhythmia. After one week of SMS treatment, gastrointestinal symptoms
like nausea and vomiting disappeared in 38 cases, while symptoms like palpitation
and shortness of breath disappeared or were significantly relieved after one course of
treatment. Among 23 cases with ventricular premature beat, 16 of these had symptoms
that disappeared after one course of treatment without using any anti-arrhythmic drugs;
4 cases with atrial fibrillation did not recover, but in these the heart rate was reduced;
and 24 cases of ventricular blockade did not show any significant change. Among
36 cases that had lowered ST segment, inverted or flattened T-wave, 18 cases had their
ST-T restored to normal after one course of treatment.
IV. Treatment of anemic cardiomyopathy

Severe anemia, with a hemoglobin level lower than 50 g/L, can induce myocardial
anoxia and myocardial fatty degeneration. The resultant myocardial hypertrophy and
cardiac dilatation in association with an ultimate decrease in myocardial reserve func-
tion, as manifested by a high cardiac output cardiomyopathy or even congestive heart
failure, is refractory for treatment. Congestive heart failure is frequently present in
clinical situations and accounts for the major cause of death in macro-erythroblastic
anemia. Chen and Chen (1996) reported the use of SMS and dopamine in resuscitating
an anemic cardiomyopathic patient from acute heart failure induced by ventricular
overload during blood transfusion.
Manifestation of cardiogenic shock induced by congestive heart failure resembles
that of the depletion syndrome in traditional Chinese medicine. Depletion can be divided
into Yin- and Yang-depletion. Yang depletion is manifested as coma, unconsciousness, cold
sweat, pale complexion, cyanotic lips, clammy limbs, incontinence, pale tongue with
thin fur, and weak or irregular pulse. The Ginseng-Aconiti Decoction is commonly pre-
scribed for the treatment of Yang depletion that should be tackled by restoring the Yang,
tonifying the Qi and preventing collapse. On the other hand, Yin depletion is mani-
fested as reddish and dry skin with slight sweating, general fever and dryness of the
mouth, weak and rapid pulse, reddish tongue with yellow fur. Treatment should focus
on benefiting the Qi, nourishing the Yin, and strengthening the pulse by astringent,
in which SMS is commonly used.
The manifestation of heart failure induced by anemia generally resembles that of
Yin depletion, with signs of Yang-deficiency of the heart. With regard to its treatment,
SMS can be used as the ‘Monarch’, and Radix Aconiti Preparata as the ‘Minister’, to
Clinical studies 61
facilitate resuscitation and prevention of collapse. According to the theory of traditional
Chinese medicine, the herbal components of SMS, namely Ginseng, Ophiopogoniae and
Schisandrae have Qi-invigorating, Yin-nourishing and tranquilizing effect, respectively,
while Aconiti Preparata has resuscitating effect. Results from recent studies indicated
that SMS was capable of 1) improving left ventricular function, enhancing myocardial
contractility and endurance in physical exercise; 2) increasing the ejection fraction of
the left ventricle and blood pressure, reversing mild and moderate shock, reducing the
dosage requirement of hypertensive drugs for treating severe shock, and reducing the
dependence on dopaminergic drugs; 3) decreasing the plasma content of β-globulin,
platelet Factor IV and TXB2, inhibiting the response of platelet activation and release;
4) reducing the permeability of blood capillaries; 5) enhancing systemic tolerance to
anoxia; and 6) reducing the area of myocardial infarction, prolonging the beating time
of ischemic heart and improving the microcirculation under conditions of cardiogenic
shock. After all, effective management of refractory heart failure induced by anemic
cardiomyopathy requires early diagnosis and prompt treatment.
V. Treatment of apical hypertrophic cardiomyopathy by SMS

Apical hypertrophic cardiomyopathy, a subtype of hypertrophic cardiomyopathy, is
a genetic disease usually found in males, with clinical manifestations being similar
to that of other types of hypertrophic cardiomyopathy. Two main diagnostic pro-
perties are described: 1) amplified inverted T-wave (>10 mm) and QRS-complex with
high voltage (Rv5 > 26 mm or Rv5 + Sv1 > 35 mm) on the electrocardiogram; and
2) concentric hypertrophy of cardiac apex observable in the left ventricular cardiograph
and 2-dimensional echocardiogram, with the apical thickness (24.8 ± 6.6 mm) being
far larger than normal (9.4 ± 3.1 mm). Ratio of apical thickness and the thickness
in mid-region of left ventricular anterior wall is significantly enhanced (1.86 ± 0.53)
when compared with normal (1.05 ± 0.24). There are only a few studies on the treat-
ment of apical hypertrophic cardiomyopathy. Some reported that nifedipine and
propranolol treatment could produce a certain degree of efficacy, with the relief of
chest pain and enhancement of endurance in physical exercise. While some studies
reported that verapamil treatment could reduce the occurrence of amplified T-wave,
others reported that such treatment could not produce significant improvement in the
electrocardiogram.
Qiu and Luo (1989) described a case of apical hypertrophic cardiomyopathy given
nifedipine and diuretics treatment. Although the symptoms of chest distress and
palpitation were relieved, this treatment regimen could not prevent the occurrence
of arrhythmia, leaving the patient at risk of sudden death. Since the case was com-
plicated with the presence of sinus bradycardia, the use of anti-arrhythmic drugs
was limited. In addition, the patient showed intensive response to the side effects
of many drugs, thereby rendering pharmaceutical intervention ineffective. In con-
trast, satisfactory therapeutic effects have been observed with SMS treatment. With
slightly more than a year of management after discharge from the hospital, the health
status of the patient has returned to normal: heart functions have been improved,
incidence of arrhythmia basically disappeared, and general mobility was enhanced.
All these findings suggested the therapeutic effect of SMS towards hypertrophic
cardiomyopathy.
VIRAL MYOCARDITIS
Myocarditis, inflammatory pathological changes of the myocardium, is mainly caused

by an infection of bacteria, viruses, fungi, and protozoa. A small number of cases are
related to toxic response or intoxification, radiation exposure, and systemic diseases
like dermatomyositis and sarcoidosis. In recent years, the incidence of rheumatic fever
or bacteria (e.g. diphtheria)-induced myocarditis has progressively decreased, whereas
viral myocarditis has become more prevalent. The latter is mostly found in young
patients, but the occurrence in children, middle-aged and elder people is not rare.
Viral myocarditis has posed a big threat to community health that can hamper the
productivity of the society. While there is still no specific treatment available for viral
myocarditis, the treatment based on the integration of Chinese and modern medicine
has obtained some successes. The following describes the use of SMS in the prevention
and treatment of viral myocarditis.
I. Pathogenesis
According to modern medicine, the pathogenesis of viral myocarditis involves (1) the
direct effect of viral invasion on the myocardium, causing damage on the microvascu-
lature and (2) indirect damage to the myocardium caused by the immune responses
associated with the disease. According to the theory of TCM, viral myocarditis belongs
to the clinical aspects of terrified palpitation, severe palpitation, cardiac obstruction,
and consumptive diseases. The pathogenesis of the disease involves the deficiency
of the primordial-Qi and pathogen invasion, while emotional status, tiredness, and
exogenous infection are factors leading to the induction of the disease. The disease can
damage the Qi, blood, Yang and Yin not only to the heart, but also to the whole body
(Sun 1995).
II. Clinical diagnosis

There is still some controversy about the diagnostic criteria for viral myocarditis. Under
clinical conditions, there are no rapid and highly specific diagnostic means available
for viral myocarditis. According to the National Forum on Myocarditis and Myocardial
Diseases held in 1987 (Editorial 1987), the diagnostic criteria for viral myocarditis
include: (1) clinical symptoms and signs (upper respiratory tract or digestive tract)
of viral infection; (2) heart performance at the acute stage or within 1–3 weeks after
viral infection, persistent and frequent pulses unrelated to feverish condition, edema,
coughing, non-productive asthma, chest distress, heart malfunctions with unknown
causes, and other signs such as cardiomegaly, cardiac murmur, the third and fourth
heart sound and arrhythmia; and (3) various arrhythmias found in the electrocardiogram:
(a) atrioventricular block or sinoatrial block, bundle branch block, (b) more than two
channels with its ST segment being lowered or elevated, or abnormal Q concentration,
(c) frequent, multiform, polyfocal or paired/parallel premature beat, burst or paroxysmal
supraventricular tachycardia and ventricular tachycardia, beating and fibrillation,
(d) frequent atrial or ventricular premature beat, (e) inverted T-wave (either bipolar or
flattened). In addition, other indications of viral myocarditis include positive response
of PCR EVS-RNA test and a four-fold increase in antibodies against Coxsackie B virus
(Zhao et al. 1996), positive response of serum creatine phosphokinase (CK) and its
Clinical studies 63
isozyme (CK-MB), and positive response of serum myocardial troponin T (cTnT) and
troponin I (cTnI). With regard to sensitivity and specificity, serum cTnI is superior to
cTnT as a diagnostic for acute viral myocarditis. In addition, cTnI also provides a
wider time window for diagnosis. Hence, serum cTnI is a highly recommended diag-
nostic marker for viral myocarditis in clinical situations. Finally, the diagnosis of viral
myocarditis should be carefully distinguished from other pathological conditions, such
as hyperthyroidism, β-adrenoreceptors hyperfunction syndrome, coronary heart disease,
rheumatic myocarditis, toxic myocarditis, and primary/secondary cardiomyopathy, that
can also affect the myocardium.
III. Clinical treatment: effect of SMS

There is no specific drug treatment available for acute viral myocarditis. The patients
of viral myocarditis should have plenty of bed rest and a sufficient nutrient intake.
With the adoption of the therapeutic method integrating modern medicine and TCM,
the recovery time for the patients is about three months (Editorial 1987). Patients
with unstable pathogenic conditions should have a longer resting time. In general, the
treatment regimen for viral myocarditis consists of the following.
A. Anti-infection treatment
For western drug treatment, ribavirin is usually used. Other anti-bacterial drugs are
given simultaneously if necessary. Regarding TCM, Double Coptidic decoction, Jade
Screen powder, Radix Sophorae Flavescentis, and Lonicerae-Forsythiae powder are the
drugs of choice (Chen et al. 1990; Sun 1998; Wang 1998). Experimental studies have
demonstrated that Radix Sophorae Flavescentis was effective against Coxsackie virus,
while Radix Astragali, SMS, and Calcui Bovis acid can enhance the immune functions
in patients suffering from viral myocarditis ( Jia 1998; Xiong et al. 1997). SMS can
benefit the vital energy (Qi) and nourish the Yin, and also produces a modulatory effect
on the cell-mediated immune function. SMS treatment can enhance the immune func-
tion of cardiomyocytes and the peripheral vascular sub-populations of T-lymphocytes,
thus improving the immune status of cardiomyocytes under the condition of viral
myocarditis.
B. Myocardial nutrients
Co-enzyme A (Co-A), co-enzyme Q10 (Co-Q10), adenosine-triphosphate (ATP), fructose-
1,6-diphosphate (FDP), and vitamins can be used. In acute treatment, ATP (40 mg)
and Co-A (200 U) supplemented to glucose (5 per cent) solutions (250 ml) with or
without FDP (10 g) are given by intravenous infusion once a day, with the course of
treatment lasting for 10–14 days, while Co-Q10 and vitamins are given orally.
C. Symptoms-oriented treatment
Patients with heart failure or arrhythmia are given standard drug treatment. If necessary,
the restoration of cardiac rhythm by direct current is given in case of severe intractable
tachycardia (supraventricular tachycardia and ventricular tachycardia). Specific treat-
ment is not required for patients with I°/II° atrioventricular block or if the ventricular
Table 3.1 Comparison between the SMS treatment group and the placebo control group in
heart function
Stroke volume (ml/beat) Cardiac output (ml/min) Cardiac index

SMS Before (n = 20) 60.6 ± 14.9 4.4 ± 1.0 2.5 ± 0.5
After (n = 20) 72.6 ± 16.2* 5.3 ± 0.9 3.1 ± 0.6*
Control Before (n = 20) 66.1 ± 8.9 4.7 ± 0.6 2.9 ± 3.8
After (n = 20) 62.3 ± 10.5 4.0 ± 1.2 2.8 ± 0.5
Values given are mean ± SD, with the number of cases indicated in parentheses.
* significantly different from that prior to the SMS treatment ( p < 0.001)
rate is more than 50 per minute. If the symptoms are obvious and the cardiac rate
is less than 50/min, the patients are given either atropine or isoproterenol orally, at
a dosage of 0.3 and 10 mg respectively, 3 times a day. And if necessary, isoproterenol
(0.5–1.0 mg) supplemented with glucose (5 per cent) solution can be given by intraven-
ous infusion. Under conditions of IIº and IIIº of Mobitz type II atrioventricular block,
a broad QRS complex being observed on the electrocardiogram or the recurrent incid-
ence of Adams-Stokes syndrome, the patients should be temporarily installed with an
artificial pacemaker.
D. Corticosteroid treatment
Whether corticosteroid hormones can be used to treat viral myocarditis is still a
controversial area. They are not used as a routine or standard treatment regimen, but
in severe cases it will be used as early as possible, for protecting the cardiomyocytes
and reducing the edema. In contrast, it should not be used at the early stage (within
10 days) of the course of general viral myocarditis.
Based on the findings from our previous studies on the effect of SMS on cardio-
myopathy and the aforementioned treatment approaches, clinical investigation of the
effect of SMS treatment on viral myocarditis has been done in the early 1990s. In this
clinical study, 35 patients with viral myocarditis were given SMS preparation (1
package is comprised of Radix Ginseng Destillata (1 g), Radix Ophiopogonis (3 g) and
Fructus Schisandrae (1.5 g); provided by The First Chinese Pharmaceuticals Factory of
Shanghai) at a dose of 3 packages (mixed with water and administered orally) per day.
In the control group, 27 patients were given the placebo preparation (caramel and
white dextrin in a ratio of 1:10; provided by the same factory) which had the same
packaging and weight as the SMS preparation. Both the control and treatment group
were given a single course of treatment, lasting for four weeks. Prior to, on the third
week, and fourth week of the drug treatment, the activities of superoxide dismutase
(SOD) and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA)
in patients’ blood were measured. Using a Doppler device for assessing heart function,
heart functional parameters such as stroke volume (SV), cardiac output (CO), and
cardiac index (CI) were measured before and after the drug treatment (Table 3.1).
Patients in both the placebo control and the SMS-treated groups were given myocardial
nutrients and other symptom-oriented medication as usual, but avoided using drugs
that could affect the lipid peroxidation. Thirty healthy people were also studied for
Clinical studies 65
Table 3.2 Activities of blood superoxide dismutase and glutathione peroxidase and level of
MDA in patients with viral myocarditis and healthy individuals
Superoxide dismutase Glutathione peroxidase Malondialdehyde

(SOD, U/g/Hb) (GSH-Px, U/g/Hb) (MDA, nmol/ml)
Viral myocarditis (n = 62) 55.94 ± 16.65* 11.69 ± 5.78* 9.40 ± 3.08*

Healthy people (n = 30) 71.94 ± 12.45 18.56 ± 2.59 5.33 ± 0.97
Values given are mean ± SD, with the number of subjects indicated in parentheses.
* significantly different from the healthy group ( p < 0.01)
Table 3.3 Effect of SMS treatment on blood superoxide dismutase, glutathione peroxidase
activities and malondialdehyde level
SOD (U/g/Hb) GSH-Px (U/g/Hb) MDA (nmol/ml)

SMS Before (n = 35) 54.61 ± 16.56 11.28 ± 26.09 9.41 ± 2.97
2 weeks (n = 18) 63.15 ± 14.90 15.02 ± 8.06 8.24 ± 2.36*
4 weeks (n = 35) 70.59 ± 18.07* 16.79 ± 6.41* 8.30 ± 2.53*
CONTROL Before (n = 27) 57.59 ± 16.91 12.20 ± 5.21 9.29 ± 3.26
2 weeks (n = 16) 56.37 ± 13.58 13.39 ± 4.59 8.08 ± 3.05
4 weeks (n = 27) 63.29 ± 20.37 14.40 ± 6.40 8.89 ± 1.95
Prior to, and on the third and fourth week of SMS treatment, the activities of superoxide dismutase
(SOD) and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) in patients’ blood
were measured. Values given are mean ± SD, with the number of subjects indicated in parentheses.
* significantly different from that prior to the SMS treatment ( p < 0.01)
comparison. The results indicated that patients with viral myocarditis were found to
have significantly lower blood GSH-Px and SOD activities than those of healthy
people ( p < 0.01), but MDA levels were significantly higher ( p < 0.01) (Table 3.2). In
the SMS treatment group, blood GSH-Px and SOD activities were significantly increased
( p < 0.01) while MDA level was significantly decreased ( p < 0.01) (Table 3.3). In the
placebo control group, SOD and GSH-Px activities and MDA level did not show any
detectable changes before and after the treatment (Table 3.3). The ensemble of results
suggested that the myocardial damage caused by viral myocarditis may be related to
the lipid peroxidative reactions, in that SMS can scavenge free radicals and inhibit
lipid peroxidation, thereby preventing the myocardial damage.
Our hospital has also participated in a clinical project, entitled ‘Treatment and
Diagnosis of Viral Myocarditis and Dilated Cardiomyopathy’, which was a strategic
topic in the ‘National Nine-Five Research Project’ started in 1996. It was a cross-
institutional project led by The Shanghai Medical University, Shanghai Second Medical
University and The Nanjing Medical University. In this study, patients suffering from
viral myocarditis (52 cases) were assigned to the SMS treatment group and treated
with a regimen comprising Radix Astragali, SMS, and Calculi Bovis acid. First of all,
40 ml of SMS injection liquid (every 10 ml was comprised of Radix Ginseng Destillata
(1 g), Radix Ophiopogonis (3 g) and Fructus Schisandrae (1.5 g), manufactured by The
First Chinese Pharmaceuticals Factory of Shanghai) was supplemented to a 5 per cent
glucose solution (250 ml), and was given to the patient by intravenous infusion once
Table 3.4 Comparison of changes in clinical symptoms and EKG/Holter results between the
SMS treatment group and control group
Chest distress Palpitation Chest pain EKG/Holter

(Number of cases)
SMS treatment Before 49 45 23 52

(n = 52) Effective 34 30 14 19
Dominant effect 4 7 4 20
Ineffective 11 8 5 13
Total number of
effective cases 38 37 18 39
Total effective rate 78% 87% 78% 75%
Control Before 50 42 21 50
(n = 50) Effective 22 25 7 13
Dominant effect 2 1 3 34
Ineffective 26 16 11 23
Total number of
effective cases 24 26 10 27
Total effective rate 48% 62% 48% 54%
p < 0.01 p < 0.05 p < 0.05 p < 0.05
a day. Radix Astragali (20–40 g) was added to a 5 per cent glucose solution and was
also given once a day by intravenous infusion. Both drug treatments were given for
14 days. Then one package of SMS oral preparation (manufactured by The First
Chinese Pharmaceuticals Factory of Shanghai) was given three times a day. ‘Healthy-
Heart’ granule preparation (manufactured by Zhongshan Hospital of Shanghai, 5 g per
package, equivalent to Radix Astragali (15 g) and Radix Sophorae Flavescentis (15 g))
was given orally, twice a day. Calculi Bovis acid was also given orally at a dose of 2 g,
three times per day, consecutively for three months. The conditions of the patients
were monitored for half a month or every month; clinical symptoms and signs, blood
biochemistry and electrocardiogram, and if necessary, a Holter examination, chest
X-ray and echo-cardiogram would be carried out. The control group (50 cases) was
given myocardial nutrients: Co-A (200U) and ATP (40 mg) added to 5 per cent
glucose solution (250 ml) for intravenous infusion; two weeks later, Co-Q10 was given
orally at a dose of 20 mg, three times per day. Both the SMS treatment and control
group were given symptom-orientated drug treatment, and all data were analyzed
by t-test to detect the inter-group differences. Results from this study indicated that
after one month of treatment the effective rate on chest distress in the SMS treatment
group was significantly higher than that of the control group, with the group differ-
ence being statistically significant ( p < 0.01). Improvements in symptoms such as
palpitation, chest distress and EKG/Holter results in the SMS treatment group were
also significantly different from those of the control group ( p < 0.05) (Table 3.4). The
effective rate on serum cTnT and cTnI in the SMS treatment group was 72 per cent
and 59 per cent respectively, while that in the control group was 43 per cent and
32 per cent respectively, with the group differences being p < 0.05 (Table 3.5). The
ensemble of results from this clinical study indicated that SMS injection liquid and
SMS oral preparation could produce good therapeutic efficacy on the treatment of
acute viral myocarditis.
Clinical studies 67
Table 3.5 Comparison of neutralized antibodies, CTnT and CTnI between the SMS treatment
group and control group
Neutralized CTnT CTnI

antibodies
SMS treatment (n = 52) No. of abnormal cases 21 29 32

before the treatment
No. of effective cases 14 21 19
Effective rate 67% 72% 59%
Control (n = 50) No. of abnormal cases 26 23 28
before the treatment
No. of effective cases 11 10 9
Effective rate 42% 43% 32%
p > 0.05 p < 0.05 p < 0.05
IV. Other reports on the efficacy of SMS treatment

As reported by Huang et al. (1999), when given ‘Erzhi pills’ (Fructus Ligustri Lucidum
and Fructus Mori Albae) and supplemented SMS in company with Co-Q10 injection,
patients with viral myocarditis were found to have a total effective rate of 91.5 per
cent, which was significantly different from the control group ( p < 0.01). Other
studies have reported that various supplemented SMS preparations were used for treat-
ing viral myocarditis and the total effective rate ranged from 81.0 per cent to 93.3 per
cent (Bu et al. 1999; Li 1995; Ying 1999; Zhu et al. 1995). As reported by Zhang H.
(1997), SMS and Radix Astragali injection liquid were used for treating viral myocarditis.
The SMS-treated group had an effective rate of 96.8 per cent (Zhang H. 1997). As
reported by Yin and Lu (1997), the total effective rate of SMS injection liquid ranged
from 92.5 per cent to 96.0 per cent (Peng et al. 1995; Tan et al. 1995; Yang 1997;
Yin and Lu 1997), whereas the use of SMS together with Lonicerae-Forsythiae powder
could produce an effective rate of 97.3 per cent, as described in Sun (1998). Zhang
P.Y. (1997) has reported that Qingkailing together with SMS injection could pro-
duce an effective rate of 92 per cent. It has also been reported that by adopting
the heart-clearing and detoxification method for expelling the toxins and SMS injec-
tion liquid for treating viral myocarditis, the effective rate was found to be 96.8 per
cent. Although these studies have reported different effective rates, all indicated
the effectiveness afforded by SMS treatment when compared with the control. The
patients given SMS oral preparation or SMS injection liquid could be relieved from
clinical symptoms and showed better recovery in heart function, electrocardiogram
marker, and biochemical indices. The effective rates of SMS treatment obtained from
these studies were generally higher than that reported by our studies (Table 3.1–3.5),
which may be due to the difference in observation period for clinical efficacy. Results
from all of these studies supported the idea that SMS oral preparation or SMS injection
liquid can produce significant therapeutic effect on treating viral myocarditis. SMS
treatment can therefore provide a therapeutic means of TCM characteristic for viral
myocarditis.
V. Mechanism of SMS treatment on viral myocarditis
Clinical studies from our laboratory have demonstrated that the protection afforded by
SMS treatment against viral myocarditis-induced myocardial damage may be attributed
to its inhibitory effect on free radicals and lipid peroxidation.
In the view of the theory of TCM, the treatment for viral myocarditis should be
primarily focused on supporting the healthy energy, which is supplemented by sedatives
and tranquilizing agents, as well as agents that can eliminate the invading pathogens.
The invigoration of healthy energy (Qi) can modulate the visceral function and re-
inforce the immune capacity. SMS can be prescribed for benefiting the vital energy
and recuperating the normal pulse condition. Ginseng, one of the component herbs,
can invigorate the primordial-Qi and vital energy, and produce a tranquilizing effect. It
can directly activate the myocardium to increase cardiac output and to improve the
microcirculation. Recent studies have demonstrated that under conditions of myocardial
ischemia-reperfusion, Ginseng could enhance the creatine phosphokinase (CPK) and pro-
stacyclin (PGI2) levels, but suppress the thromboxane A2 (TXA2) level, thereby maintain-
ing the beneficial balance between PGI2 and TXA2 (Chen et al. 1989; Xu and Liu 1991;
Yao et al. 1988). In addition, the Ginseng-derived saponins could enhance the PGI2
synthesis, but inhibit the thromboxane synthesis (Deng and Luo 1992). The saponins
could also inhibit the free radical production from activated polymorpholeukocytes
and neutrophils (Deng and Luo 1992). Furthermore, Ginseng could increase the level of
endogenous glucocorticoid and activate the reticuloendothelial system. Fructus Schisandrae,
another component herb, can produce an astringent action on the lungs, nourish the
kidney, promote body fluid production, prevent excessive perspiration and produce a
stimulatory effect on the central nervous system and respiratory system (Yang and Xie
1998). It can also act synergistically with Ginseng to activate the adrenocortical func-
tions. Radix Ophiopogonis, also a component herb, can produce bacteriostatic effect and
hyperglycemic effect, and resist the ischemic damage. Some studies have reported that
SMS injection liquid did not produce bacteriostatic effect (Chu et al. 1984); instead, it
could inhibit the histamine or 60CO-exposure induced enhancement in capillary per-
meability, indicating the ability of SMS to produce non-specific anti-inflammatory
actions. Glucocorticoid is one of the important endogenous anti-inflammatory agents,
and prostaglandin E is an active agent for vascular endothelium relaxation, sensation
of pain and inflammation. While SMS injection liquid can significantly increase the
level of endogenous glucocorticoid in experimental animals and healthy individuals,
this action is particularly important under the condition of adrenocortical insufficiency
caused by infectious stress stimulation. On the other hand, SMS injection liquid can
reduce the level of plasma prostaglandin E in experimental animals, which is import-
ant for the maintenance of tension of vascular endothelial muscle and the suppression
of inflammatory responses. These two pharmacological actions produced by SMS
injection liquid form the pharmacological basis of therapeutic actions in the treatment
of septic shock. The immune system is an important component of the endogenous
defensive system against infection, the decline in immune function can increase the
chance of infection. While infection can induce specific immune responses, it can
also simultaneously inhibit the non-specific immune responses. Research studies have
indicated that SMS injection liquid could significantly activate the phagocytic function
of the macrophage system and suppress the IgE-mediated humoral immunity, resulting
in the priming of immune function to a relatively activated status.
Clinical studies 69
In summary, as judged both on the basis of TCM and results obtained from experi-
mental and clinical studies, SMS oral preparation/SMS injection liquid was found to
produce anti-inflammatory and immunomodulatory. It also protects myocardial tissue
against ischemic damage, thereby producing beneficial effect on the prevention of dis-
ease progression and treatment of viral myocarditis. In addition, the immunomodu-
latory effect produced by SMS treatment can prevent the occurrence of recurrent viral
myocarditis. Experimental and clinical findings from our laboratory suggested that in
addition to the use of western medications like anti-infection drugs and myocardial
nutrients, SMS injection liquid could be given during the acute phase of viral
myocarditis, and SMS oral preparation could be administered later on. The combined
treatment could enhance the recovery, reduce the course of disease, and strengthen the
health condition of patients suffering viral myocarditis. SMS is therefore regarded as a
good example of an old drug for new use.
HEART FAILURE
Heart failure is a commonly occurring clinical syndrome with a high mortality rate.
The incidence of heart failure increases with age, and appears to be higher in males.
Pathological changes associated with heart failure, including valvular disease, hyper-
tension, atherosclerosis-related ischemic heart disease, myocardial infarction, cardiac
hypertrophy, and pulmonary heart diseases, can eventually lead to the development of
heart failure. Clinical manifestations of heart failure include symptoms of insufficient
pulmonary circulation such as dyspnea, coughing, expectoration and hemoptysis, as
well as symptoms of reduced cardiac output such as hypodynamia, cyanosis, tachycardia,
and hypotension. Clinical signs and symptoms of insufficient systemic circulation such
as sustained insufficient blood perfusion of organs, edema, jugular filling, swelling and
tenderness of the liver, and pleuroperitoneal edema could also be found.
Digitalis, which has been used clinically for two hundred years, is still an effective
drug available for the treatment of heart failure nowadays. Digitalis preparations can
enhance the cardiac efficiency under conditions of heart failure through increasing
myocardial contractility, reducing and prolonging the systolic and diastolic period,
respectively, reducing the heart volume, inducing peripheral vasodilatation, increasing
the cardiac output, and reducing the myocardial oxygen consumption. In addition to
digitalis, diuretics, which are able to decrease the water and sodium retention in the
body and thereby reduce the cardiac workload, play an important role in the treat-
ment of heart failure. However, it is found that standard treatment using digitalis and
diuretics sometimes cannot manage refractory heart failure. Under such conditions,
only multiple drug treatment can work efficaciously. In this regard, SMS injection
liquid has been effectively used for the treatment of heart failure in clinical situations.
The clinical efficacy of SMS injection liquid was corroborated by experimental studies
which suggested the mechanism involved in the cardio-enhancing effect of SMS.
A huge volume of clinical evidence has shown that SMS injection could produce
good therapeutic efficacy on heart failure and cardiogenic shock caused by coronary heart
disease, myocardial infarction, myocarditis, dilated cardiomyopathy, and pulmonary
heart diseases (Wang et al. 1994). Prior to the drug treatment, the patients selected for
the clinical investigation were assessed for blood viscosity, platelet adhesion and aggrega-
tion, and heart function including stroke volume, cardiac output, cardiac index, ejection
index, peripheral vascular resistance, left ventricular systolic and diastolic internal radii,
and shortening rate of left ventricular axis. In addition, three of the main standard
cardiac parameters such as cardiac rate, electrocardiogram, and thoracic X-ray were also
examined. In addition to the standard medication, the treatment group was given SMS
injection liquid (80 ml) in a 5 per cent glucose adjuvant (500 ml) by intravenous infu-
sion, consecutively for 2 weeks. After the SMS treatment, the aforementioned measure-
ments were repeated for comparison. The results indicated that there were significant
(P < 0.01) differences in terms of blood viscosity, blood platelet adhesion and aggrega-
tion, as well as heart function in patients before and after the SMS treatment, with
the mortality rate being also significantly reduced (Wang et al. 1994). It was found
that the whole blood viscosity, plasma viscosity, and hematocrit were significantly
increased in patients with heart dysfunctions. Results obtained from experimental and
clinical studies suggested that the reduction of blood viscosity by SMS treatment in
patients with heart dysfunctions may be related to a number of actions. SMS treatment
can suppress platelet aggregation and release, promote blood circulation by activating
the blood flow, and increase both the cardiac output and the velocity of blood flow by
enhancing the myocardial contractility. The resultant improvement in anoxic condition
could enhance the morphological changes of erythrocytes, which, in turn, reduce the
blood viscosity and improve the heart function. After SMS treatment, the majority of
the patients were found to have a relief in symptoms such as coughing, expectoration,
palpitation, short breath, and dyspnea, to a varying extent. In addition, paroxysmal
dyspnea occurring at night was relieved, with the cardiac rate being reduced, the noise
from the lungs being decreased/disappeared and the heart sound being strong. Urinary
volume of edematous patients was increased, with the extent of edema being decreased
to varying degrees. After the SMS treatment, parameters from regular blood and urine
analysis, measurements of blood platelet activities, and hepatic and renal functions
remained normal. There were no derangements in blood sugar level, blood lipids level,
and electrolyte balance. Except for a few individual cases of fever and skin eruption, no
severe side effect was observed (Wang et al. 1994). The hemodynamic effects produced
by SMS in patients suffering from heart failure are described as follows.
I. Enhancement of heart pumping function

After the intravenous infusion of SMS injection liquid, both cardiac output and stroke
volume were increased to varying degrees. Noting that SMS could enhance the stroke
volume and concomitantly decrease the peripheral vascular resistance in patients with
abnormal left ventricular filling pressure, the pharmacological action produced by
SMS seemed to be different from that of vasodilators. Vasodilators can only increase
the stroke volume under conditions of higher left ventricular filling pressure than the
normal upper limit, flat heart functional curve, and reduced after-load. In contrast
to vasodilators, SMS can enhance the cardiac output under different cardiac loading
conditions, and improve the pump function under the condition of heart failure.
On one hand, these effects could be attributed to the ability of SMS to decrease the
resistance against both systemic circulation and left ventricular ejection, so as to
increase the stroke volume. On the other hand, the observation that SMS could increase
the stroke volume under the condition of low left ventricular filling pressure suggests
the ability of SMS to enhance myocardial contractility. The positive ionotropic action
of SMS is similar to that of lanatoside, but, without the toxic effect associated with
Clinical studies 71
digitalis. Furthermore, SMS could enhance the prostacyclin synthesis and inhibit the
thromboxane synthesis, as well as selectively antagonize the blood platelet-activating
factors. As a consequence, the blood viscosity and the extent of platelet adhesion and
aggregation are significantly reduced, leading to a condition favorable to the removal
of blood stasis in small blood vessels and hence reduction in the resistance of micro-
circulation and improvement in both myocardial blood flow and metabolism. As SMS
injection liquid can improve the heart function through fundamental means, it serves
as an effective drug for the treatment of heart failure, with its effective period being
longer than that of the conventional drug, dopamine.
II. Enhancement of heart function without the increase in

myocardial oxygen consumption
Clinical studies have shown that one hour after the administration of SMS injection
liquid, patients suffering from myocardial infarction were found to have LVET being
significantly prolonged, PEP, ICP being reduced, PEP/LVET ratio being decreased,
LVET/ICT ratio being increased, and cardiac rate and peripheral vascular resistance
being reduced. All these significant changes indicated that SMS injection liquid could
enhance the left ventricular contractility, stroke volume and cardiac output, without
causing any increase in the myocardial oxygen consumption but maintaining the
balance between oxygen demand and supply to the myocardium.
III. Invigoration of the heart-Qi

According to the theory of TCM, the heart controls the blood circulation, and the
continuous movement of blood inside the vessels is driven by the heart-Qi which can
be regarded as the pumping function of the heart. The pathogenesis of heart failure
involves both asthenia in the body constitution (visceral ) and sthenia in superficiality
(surface). Diagnosis based on asthenia syndrome indicates that heart failure is likely
to be associated with Qi-deficiency and deficiency of both the Qi and the Yin. Qi is
the driving force for the functionality of organs; primordial-Qi deficiency can cause the
decline in visceral functions and the insufficiency in energy transformation (hence
the Qi and the Yin deficiency), which, in turn, affect the nourishment of the heart
(Cao 1997). Deficiency of the Qi is found to be associated with an impediment in
blood circulation, as clinically manifested by the weak pulse condition and blood stasis,
as well as palpitation. The spleen asthenia can cause the inability to transform the
dampness, whereas kidney asthenia can lead to edema arising from the retention of body
fluid. The accumulated dampness can attack the lung and cause the shortness of breath,
with coughing and dyspnea on lying posture (Cao 1997).
Radix Ginseng, which serves as the ‘Monarch’ (the chief drug) in the SMS formula,
can supplement the lung function and invigorate the Qi in the channels connecting
to the lung, spleen and heart. It is therefore capable of invigorating the primordial-Qi,
supplementing the spleen and lung function, promoting production of body fluid and
tranquilization. Radix Ophiopogonis, which serves as the ‘Minister’ (assistant drug),
can act through the channels to the lung, heart and kidney, so as to benefit the Qi and
promote the production of body fluid, supplement the kidney function, and nourish the
heart. Fructus Schisandrae can produce the astringent function, retain the lung-Qi and
stop excessive perspiration for promoting production of body fluid. The combined use
of these three herbs, which produce a supplementing, clearance and astringent action,
respectively, can benefit the Qi, nourish the Yin, promote the production of body fluid
production to quench thirst and preserve the Yin to prevent collapse. These effects can
result in the replenishment of the Qi, restoration of the normal pulse, and preservation
of the Yin by reducing perspiration, eventually leading to the restoration of visceral
functions and the strengthening of the body constitution. Modern pharmacological
studies have indicated that the principal ingredients of SMS injection liquid include
ginsenosides, organic acid, schisandrins, various trace elements, and other saponins.
These active components of SMS can enhance the organ function and modulate the
body metabolism, thereby relieving the symptoms of chest distress, palpitation, hypo-
dynamia and excessive perspiration. These actions are analogous to the replenishment
of the Yin, the Yang, the Qi, and the blood for relieving various asthenia symptoms in
TCM. Hence, the fundamental principle underlying the treatment of heart failure should
be focused on invigorating the Qi, while the enhancement of cardiac pump function
and cardiac output are equivalent to the Qi-invigorating as described in TCM.
In summary, SMS injection liquid can effectively treat heart failure caused by
cardiac hypertrophy, rheumatic and pulmonary heart diseases. It can also be used for
treating heart failure patients who are non-responsive to digitalis treatment.
CARDIOGENIC SHOCK
Shock is a sudden decrease in tissue perfusion and oxygen supply induced by an acute
circulatory disturbance, with clinical manifestations of a series of metabolic and func-
tional disorders. While the incidence of shock can be originated from various diseases,
cardiogenic shock is more prevalent. Despite the recent advance in the therapy and
prevention of shock, the mortality rate of shock still remains at a high level. Hence,
further investigation on the treatment of shock is necessary.
According to our clinical experience and reports from other hospitals in China,
SMS has been widely used as a supplementary regimen for the treatment of shock (Li
1997; Wang and Zhou 1995). While being used together with standard therapeutic
intervention for shock symptoms, SMS injection liquid could enhance the cardiac
output, with blood pressure being progressively increased, limb temperature being
restored, urine volume being increased, perspiration being reduced, and mental
status being tranquilized. The clinical efficacy afforded by SMS injection liquid was
significantly higher than that of the control group (i.e. without supplementary SMS
treatment). After the termination of vasoactive drug administration, the blood pressure
was maintained to a better extent than that of the control group. In general, early after
the onset of myocardial infarction, the peripheral vascular resistance is increased by
the endogenously secreted catecholamines. Under such conditions, the use of sym-
pathomimetic drugs for elevating blood pressure can further jeopardize the peripheral
circulation, leading to symptoms such as clammy limbs and reduction of urine volume.
Through resolving the contradictory action of hypertensive drugs in the increase of
both coronary blood flow and peripheral resistance, SMS injection liquid can enhance
the cardiac output, with the arterial pressure being increased, and peripheral resist-
ance being decreased. The blood pressure modulatory effect of SMS injection liquid
is relatively mild, without producing abrupt changes in blood pressure as in the
case of hypertensive drug treatment. Being endowed with the Qi invigorating, pulse
Clinical studies 73
recuperating and collapse preventing actions, SMS injection liquid is a reliable treatment
for cardiogenic shock. However, the relatively slow blood pressure elevating effect of
SMS warrants the application of other anti-shock therapeutic interventions, particularly
on the primary cause of the disorder.
RESPIRATORY FUNCTION IN CHRONIC OBSTRUCTIVE

PULMONARY DISEASE
Patients suffering from chronic obstructive pulmonary disease (COPD) are often
complicated by the decline in lung and respiratory function, which is related to the
contractile dysfunction of the diaphragm. SMS has been shown to enhance the con-
tractile strength of the diaphragm in rats (Zhao and Niu 1995). Fang et al. (1998)
reported that patients suffering from COPD were treated with SMS (100 ml/day, i.v.)
for 14 days and parameters, including lung vital capacity (VC), forced vital capacity
(FVC), forced vital capacity of the first second (FEV1), FEV1/FVC, maximum voluntary
ventilation (MVV), maximum inspiratory pressure (MIP), load respiratory time (LT),
6 minute walk distance (6MWD), arterial blood gas and Borg dyspnea scale, were
examined before and after the treatment. It was found that all parameters except for
FVC and FEV1/FVC were improved by the SMS treatment, and they were significantly
better than the control group. The results suggested that SMS treatment could
improve respiratory function in COPD.
REFERENCES
Bu, C.D., Zhao, Y.J., and Sun, F.J. (1999) The application of modified Shengmai San for the
treatment of 13 cases of viral myocarditis, Chinese Journal of Integrated Traditional and Western
Medicine in Intensive and Critical Care, 6(2), 92.
Cao, G.M. (1997) The traditional Chinese medicine perspective and its therapeutic approach of
heart failure, Journal of Shanxi College of Traditional Chinese Medicine, 20(3), 6.
Chen, B. and Chen, Y.F. (1996) Treatment of 2 cases of heart failure associated with anemic
cardiomyopathy, Xiandai Zhongyi, 30(1), 48–50.
Chen, G.Z. and Wu, X.R. (1996) Treatment of refractory ventricular arrhythmia with the com-
bined use of FDP, berberine, XinBaoWan and modified SMS, Journal of Shantou University
Medical College, 2, 90–1.
Chen, L., Rong, Y.Z., and Han, Y.S. (1989) Cardioprotective effect of diltiazem against ischemia/
reperfusion injury, Shanghai Journal of Medicine, 12(12), 697–700.
Chen, S.X., Chang, P.L., Zheng, X.J., et al. (1990) Effects of the treatment of Coxsackie virus-
induced myocarditis with Yupingfeng San and Shengmai San, Chinese Journal of Integrated
Traditional and Western Medicine, 10(1), 20–1.
Chen, Y.N. (1997) Clinical study on the combined use of Shengmai Tonic and Astragali Tonic
in the treatment of arrhythmia associated with chronic hepatitis, Liaoning Journal of Traditional
Chinese Medicine, 24(9), 408.
Chu, Y., Pan, D.B., and Yang, Y.Q. (1984) Anti-inflammatory action of Shengmai injection
and its effect on the immune system, Yixue Tongbao, 19(7), 23–6.
Cong, Y.Z. (1980) Studies on Shengmai injection, Chinese Patent Medicine Research, 2, 41–3.
Deng, X.W. and Luo, D.C. (1992) Effects of SMS on the left ventricular functions, exercise
tolerance and oxygen-derived free radicals in angina patients, Chinese Journal of Internal
Medicine, 31(4), 113–6.
Department of Cardiology, Xinhua Hospital (1999) Clinical studies on the treatment of angina
pectoris with SMS injection, Proceedings of the 5th National Conference on Integration of Traditional
and Western Medicine for the Prevention and Treatment of Coronary Heart Disease, Angina Pectoris
and Arrhythmia, p.32–5.
Dong, Q.Z., Chen, K.J., Tu, X.H., et al. (1984) Effects of Shengmai San treatment on the hemo-
dynamics of patients of acute myocardial infarction, Chinese Journal of Cardiology, 12(1), 5–8.
Du, D.S., Song, Y., Xu, Q., and Meng, X. (1998) Clinical effects of SMS injection on arrhythmia
associated with hyperthyroidism, Journal of Practical Integrated Traditional and Western Medi-
cine, 11(8), 702–3.
Editorial of the Chinese Journal of Internal Medicine (1987) Proceedings of the National Forum
on Myocarditis and Myocardial Diseases, Chinese Journal of Internal Medicine, 26, 597–601.
Fang, J., Jiang, J., and Luo, D.C. (1987) Effects of SMS tonic in the heart functions of patients
with coronary heart disease, Chinese Journal of Internal Medicine, 26(7), 403–6.
Fang, Z.J., Jiang, H.M., and Wang, L.H. (1998) Therapeutic effect of Shengmai injection on
respiratory function in chronic obstructive pulmonary disease, Chinese Journal of Integrated
Traditional and Western Medicine, 9, 520–2.
Guo, S.K. (1981) Clinical study on the use of dl-demethylcolarine and SMS infusion in the
treatment of bradycardia, Beijing Medical Journal, 1, 46–7.
Hua, M.Z. and Qi, H. (1996) Treatment of 65 cases of acute myocardial infarction in senile
patients with a modified formulation of Shengmai San, Chinese Journal of Integrated Traditional
and Western Medicine in Intensive and Critical Care, 3(6), 259–60.
Huang, J.X., Han, Z.X., Su, X.Y., et al. (1999) Effects of the combined use of Shengmai
San, modified Erzhi Wan and coenzyme-Q10 injection for the treatment of viral myocarditis,
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care, 6(3),
129–31.
Huang, N., Chen, Y., and Zhou, M. (1993) Protection of the myocardium against ischemia-
reperfusion injury by Shengmai San, Journal of the First Military Medical University, 13(1),
43–6.
Jia, W.H. (1998) Clinical effects of Astragli-supplemented Shengmai San on the treatment
viral myocarditis, Chinese Journal of Experimental Traditional Medical Formulae, 4(2), 35–7.
Jiang, J., Fang, J., and Luo, D.C. (1988) Effects of SMS on the left ventricular functions and
exercise endurance of patients with dilated cardiomyopathy, Chinese Journal of Cardiology,
16(2), 65–7.
Li, C.Q. (1997) Clinical observations of the treatment of 32 cases of shock associated with early
phase of infection, Dangdai Yishi Zazhi, 2(6), 50.
Li, G.H., Xuan, M.D., Zhou, H.C., et al. (1994) Protection of the myocardium by Shengmai
tonic in open-heart surgery, Journal of Hunan Medical University, 19(5), 413–6.
Li, H.L. (1978) Treatment of cardiogenic shock associated with acute myocardial infarction,
Heilongjiang Medical Journal, 6(3), 7–8.
Li, M.J., Yang, J.X., Wang, X.L., et al. (1999) Effects of SMS injection on the exercise endur-
ance, cardiogram and blood viscocity of patients with angina pectoris, Journal of Emergency
Syndromes in Traditional Chinese Medicine, 14(2), 138.
Li, S.P. (1995) Treatment of 42 cases of viral myocarditis with a modified formulation of
Shengmai San, Shanxi Zhongyao, 16(9), 411.
Liu, X.G., Zhao, Q., Zhou, Z.P., et al. (1978) Effects of SMS on DNA metabolism in the
myocardium, Shanxi Xin Yiyao, 4, 6–9.
Lu, B.J., Rong, Y.Z., Zhao, M.H., Huang, G.F., Zhu, X.Y., and Yang, J.W. (1994) Protection
against lipid peroxidation by SMS in acute myocardial infarct patients, Chinese Journal of
Integrated Traditional and Western Medicine, 14(12), 712– 4.
Lu, H.X., Zhang, G.L., and Liu, H.Y. (1997) Treatment of heart failure in dilated cardiomyo-
pathy with the combined use of SMS and dopamine, Chinese Journal of Integrated Traditional
and Western Medicine in Intensive and Critical Care, 4(5), 112–3.
Clinical studies 75
Lu, S.B., Lu, B.J., Li, J.X., et al. (1998) Effects of SMS injection on the blood viscosity, platelet
aggregation and left ventricular function in patients with coronary heart disease, Tianjin
Yiyao, 26(4), 226–8.
Mo, Z.Z., Zhuang, R.X., Li, R.J. et al. (1997) Combined use of SMS and atherosclerotic plague
solubilizing agent – urokinase, in the treatment of acute myocardial infarction, Chinese Journal
of Integrated Traditional and Western Medicine in Intensive and Critical Care, 4(11), 487–9.
Pathophysiology Research Group, Beijing Medical University (1977) Study of cardiogenic
shock IV, Journal of Beijing Medical University, 2, 101– 4.
Pathophysiology Research Group, Beijing Medical University (1978), Experimental studies on
cardiogenic shock VII, Journal of Beijing Medical University, 4, 222–5.
Peng, W.H., Zhang, Z.G., Wang, Z.R., et al. (1995) Treatment of 40 cases of viral myocarditis
with Shengmai injection, Medical Recapitulation, 1(10), 463– 4.
Qin, L.M., Yang, J.D., and Liao J.Z. (1983) Effects of SMS on the ATPase activities of cardio-
myocytes in rats, Chinese Journal of Critical Care Medicine, 3(2), 6–8.
Qiu, R.X. and Luo, Z.Q. (1989) Clinical application of SMS for the treatment of coronary heart
disease, New Journal of Traditional Chinese Medicine, 7, 14–6.
SATCM, P.R.China (1995) Experimental and 219 cases of clinical studies of SMS injection in
the treatment of coronary heart disease, Journal of Emergency Syndromes in Traditional Chinese
Medicine, 4(4), 152–5.
Shi, Z.X., Liao, J.Z., Wu, Z.M., et al. (1981) Experimental and clinical studies of Shengmai
San, Journal of Traditional Chinese Medicine, 12, 947–51.
Su, H.H. (1998) Clinical study of the treatment of asymptomatic myocardial ischemia with
Shengmai injection, Chinese Journal of Integrated Traditional and Western Medicine, 11(10), 897.
Sun, C.X., Zhang, H.M., and Li, Y.H. (1995) Study on the treatment of 20 cases of arrhythmia
with SMS, Hebei Journal of Traditional Chinese Medicine, 17(2), 52–6.
Sun, D.X. (1998) The combined use of Shengman San and Yinqiao for the treatment of 37 cases
of viral myocarditis, Forum on Traditional Chinese Medicine, 13(2), 26.
Sun, L. and Wang, M. (1998) Clinical studies on the treatment of unstable angina with SMS
injection, Journal of Chinese Medicine and Pharmacology, 6, 23– 4.
Sun, Y. (1995) Study on the treatment of viral myocarditis: application of Shengmai San-
related formulations, Zhejiang Journal of Traditional Chinese Medicine, 30(9), 423– 4.
Tan, J.C., Xie, H.F., and Zhang, C.Y. (1995) Treatment of 30 cases of viral myocarditis with
Shengmai injection, Hebei Journal of Traditional Chinese Medicine, 17(4), 47–8.
Tan, S.J. (1997) Clinical effects of Shengmai injection and dobutamine on the treatment of
severe heart failure, Journal of Practical Integrated Traditional and Western Medicine, 10(21),
2135–6.
Tianjin Nankai Hospital (1973) Clinical studies in 105 cases of acute myocardial infarction
with an integrated approach of traditional Chinese and modern medicine, Tianjin Yiyao, 1,
10–18.
Wang, J., Sheng, J., Xu, Z.J., et al. (1999) Effects of SMS treatment on the symptoms and the
levels of antithrombin III, thromboxane B2 and prostaglandin F1α in patients with coronary
heart disease, Chinese Journal of Integrated Traditional and Western Medicine, 19(4), 256.
Wang, J.H. and Yu, C. (1997) Effects of SMS injection on the treatment of positive ventricular
late potential associated with coronary heart disease and hypertension, West China Journal of
Pharmaceutical Sciences, 12(3), 201–2.
Wang, W.X., Yan, Q.H., Hu Q.K., et al. (1997) Treatment of angina pectoris with SMS
injection, Chinese Journal of New Drugs and Clinical Remedies, 16(4), 249–50.
Wang, Y.M. and Zhou, L.Y. (1995) Treatment of cardiogenic shock by high doses of Shengmai
injection, Journal of Changchun College of Traditional Chinese Medicine, 11(49).
Wang, Z.C. (1998) The combined use of Shuanghuanglin injection and Shengmai injection for
the treatment of 40 cases of acute viral myocarditis, Journal of Changchun College of Traditional
Chinese Medicine, 14(1), 13.
Wang, Z.H., Zhang, J.Z., and Tu, Y.S. (1994) Effects of Shengmai injection treatment on the
clinical manifestations and hemodynamics of patients with impaired heart functions, Journal
of Clinical Cardiology, 9(3), 190.
Xiong, D.D., Su, Y.G., Yang, Y.Z., and Chen, H.Z. (1997) Combined use of taurine from
Astragali and Co-Q10 for the treatment of viral mycarditis, Chinese Journal of Cardiology,
25(5), 329.
Xu, Q.Y., Wang, H.C, and Liu, W.X. (1986) Effects of SMS injection on the formation of
blood-stasis in vitro and the blood clotting system in rabbits, Chinese Journal of Integrated
Xu, X.S. and Liu, C.X. (1991) Mechanism of ischemia/reperfusion injury in the myocardium
and its prevention and treatment with traditional Chinese medicine, Chinese Journal of Integrated
Yang, F.Q. and Xie, W.H. (1998) Effects of Shengmai injection and the method of heat-evil
clearing on the treatment of juvenile viral myocarditis, Inner Mongolia Journal of Traditional
Chinese Medicine, 17(3), 8–9.
Yang, H.B. (1997) Clinical study on the treatment of viral myocarditis with Shengmai injection,
Journal of Chinese Medicine and Pharmacology, 25(3), 11.
Yao, M., Rong, Y.Z., Wen, W.H., et al. (1988) Prevention of ischemia-reperfusion injury
in cardiomyocytes by Shengmai San treatment, National Medical Journal of China, 68(6),
313–5.
Yin, Y.C. and Lu, Z.F. (1997) Treatment of viral myocarditis with Shengmai injection, Journal
of Practical Integrated Traditional and Western Medicine, 10(15), 1477–8.
Ying, A.L. (1999) Treatment of 30 cases of viral myocarditis with a modified formulation of
Shengmai San, Journal of Practical Traditional Chinese Medicine, 15(3), 8.
Yuan, Y.X. and Zheng, B.D. (1997) Integration of traditional Chinese medicine and western
medicine for the treatment of intractable heart failure associated with dilated cardiomyopathy,
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care, 4(5),
202–3.
Zeng, J.S. (1996) Treatment of coronary heart disease with a modified formulation of Shengmai
San: effects on the ventricular late potential, Chinese Journal of Integrated Traditional and
Western Medicine in Intensive and Critical Care, 3(10), 448–9.
Zhang, D.N., Ni, J.X., Zhang, L.R., et al. (1984) Treatment of myocardial infarction with
Shengmai injection, Journal of Sichuan Medical University, 15(2), 131–5.
Zhang, G.Z., Zhu, K.R., and Yan, P.Q. (1997) Effects of Shengmai injection on 40 cases of
dilated cardiomyopathy, Clinical Focus, 12(7), 316–8.
Zhang, H. (1997) The application of ‘Treatment by the differentiation of signs and symptoms’
in different stages of dilated cardiomyopathy, Anhui Zhongyi Linchuang Zazhi, 9(3), 135.
Zhang, J., Wang, Z.H., and Yu, S.M. (1990) Effects of SMS on the hemodynamics of patients
with dilated cardiomyopathy-associated heart failure, Journal of Hunan Medical University,
15(2), 153–5.
Zhang, P.Y. (1997) Treatment of acute viral myocarditis with the combined use of Qingkailing
and Shengmai injection, Journal of Emergency Syndromes in Traditional Chinese Medicine, 6(6),
265–6.
Zhang, X. (1998) Study on the use of Astragali injection for the treatment of viral myocarditis,
Chongqing Medical Journal, 27(2), 124–5.
Zhang, Z.Y. and Yang, Z.W. (1986) Effect of SMS injection in the hemodynamics and oxygen
consumption of the cardiomyocytes in anesthetized animals, West China Journal of Phar-
maceutical Sciences, 1(2), 86–90.
Zhao, J.P. and Niu, R.J (1995) Effects of Shengmai injection on the contractility of the dia-
phragm under chronic hypoxic conditions in rats, Chinese Journal of Tuberculosis and Respiratory
Diseases, 18(1), 53.
Clinical studies 77
Zhao, M.H, Rong, Y.Z., Lu, B.J., et al. (1996) Effects of Shengmai San on the serum lipid
peroxides levels in patients with acute myocarditis, Chinese Journal of Integrated Traditional
and Western Medicine, 16(3), 142–5.
Zhou, H.Y. (1996) Treatment of frequent premature beat with the combined use of Astragali-
supplemented SMS, amiodarone and high doses of oryzanol, Chinese Journal of Integrated
Traditional and Western Medicine in Intensive and Critical Care, 3(7), 296.
Zhou, Y., Deng, S.Y., Shu, S., et al. (1997) Effect of SMS on the dilating function of the left
ventricle, Gui Zhou Yi Yao, 21(2), 83–5.
Zhu, Q.L. and Qiao, L.X. (1998) Combined use of Shengmai San and fructose-1,-6-bisphosphate
in the treatment of acute myocardial infarction with atrioventricular blockade, Chinese Journal
of Integrated Traditional and Western Medicine in Intensive and Critical Care, 5(3), 108.
Zhu, Q.R., Wang, Q., and Wan, Y.E. (1997) Combined use of SMS and western medicine in
the treatment of arrhythmia, Chinese Journal of Integrated Traditional and Western Medicine in
Intensive and Critical Care, 4(5), 233–5.
Zhu, Q.R., Wang, Y.E., and Wang Q. (1995) Effects of the combined use of SMS and nicot-
inamide on the treatment of senile bradycardia in 168 patients, Chinese Journal of Integrated
Traditional and Western Medicine in Intensive and Critical Care, 2(6), 246–8.
Zhu, R.F., Liu, Z.J., and Sun, Y. (1995) Treatment of 63 cases of viral myocarditis with a
modified formulation of Shengmai San, Shandong Journal of Traditional Chinese Medicine,
14(5), 207–8.
78 Zhi-Min Xu and Ye-Zhi Rong
4 Side effects of Shengmai San

Zhi-Min Xu and Ye-Zhi Rong
[Translated by Kam-Ming Ko]
Shengmai San (SMS), a traditional Chinese medicine (TCM) formula now existing in
various pharmaceutical preparations, is comprised of Radix Ginseng, Radix Ophiopogonis
and Fructus Schisandrae (1:3:1.5, w/w). Radix Salviae Miltiorrhizae is usually selected as
a substitute for the Ginseng component in SMS because of its similar Qi-invigorating
property. Radix Ginseng/Radix Salviae Miltiorrhizae is the principal pharmacological
component in the formulation of SMS that can produce positive inotropic, peripheral
vasodilating, and blood viscosity-lowering effects. However, because of its warm-heat
nature and bi-directional pharmacological properties, administration of Radix Ginseng/
Radix Salviae Miltiorrhizae may exaggerate the symptoms of Yang hyperactivity in the
already Yang-hyperactive patients. On the other hand, Radix Ophiopogonis and Fructus
Schisandrae are effective Yin-nourishing herbs, the combined use of these herbs with
Radix Ginseng/Radix Salviae Miltiorrhizae can offset the side effects of Radix Ginseng/
Radix Salviae Miltiorrhizae, thereby preventing the incidence of imbalance between
Yin and Yang in the patients given SMS treatment. Nevertheless, patients with appar-
ent hyperactive Yang should avoid using SMS to prevent the exaggeration of Yin-Yang
imbalance. Yang hyperactivity is clinically manifested as distention of head, headache,
dizziness and restlessness, and is usually associated with strong pulses, tongue redness
with little fur and yellowish urine. Furthermore, SMS should not be prescribed for
patients with pyretic and sthenia syndromes, such as uncontrolled acute inflammatory
responses (fever, infection, icterus, etc.). Hence, SMS treatment should only be applied
on the basis of Differentiation of Signs and Symptoms so as to avoid the incidence of
unfavorable side effects.
Clinical observations on the long-term use of SMS have indicated that SMS did
not produce any unfavorable effects on the hepatic/renal functions, hemopoietic system
or endocrine system. However, some scarce incidences of unfavorable side effects have
been observed in the clinical use of SMS-related preparations. In the present review,
we classified the side effects into two main categories: 1) extrinsic, those related to
the nature of the pharmaceutical preparation per se, and 2) intrinsic, unrelated to the
pharmaceutical preparation. We also tried to define the underlying mechanisms of
these side effects from the TCM perspective. It was found that most of the side effects
observed under clinical situations were related extrinsically to the nature of pharma-
ceutical preparation rather than intrinsically to SMS itself.
Side effects 79
EXTRINSIC SIDE EFFECTS
I. Anaphylaxis and drug rash

Almost all drug-induced anaphylactic responses/rash associated with injection of phar-
maceutical preparations were observed during or after the injection process. These side
effects include scarlet fever-like rash or multiple typhus (Hao et al. 1997), which are
characterized by their irregular and crowded distribution, bright red color (colorless
upon pressing), and usually, itchy sensation. Rash usually appears around the trunk,
neck, face, and upper limbs, possibly associated with light to mild fever (<38.5°C), and
occurring within one to two weeks after the drug treatment or without any apparent
latent period. Under normal circumstances, the rash would disappear 3 to 4 days
after discontinuation of drug treatment, without leaving any scar on the skin. Yet, in
case of generalized severe rash, hormonal or anti-allergic treatment would be needed.
Xu (1998) has reported a case of exfoliative dermatitis associated with the use of SMS
injection. Medical personnel should be aware of the importance of such reports. A
minority of patients may develop the dangerous side effect of anaphylactic shock (Ren
and Xia 1997; Xin 1999). Because of their life-threatening potential, prompt medical
attention should be taken should symptoms of anaphylactic shock appear during SMS
infusion. Such symptoms include idiopathic chest distress, shortness of breath, pale
complexion or blood pressure decline.
The development of drug rash may be related to the action of individual constituents
or attributed to the presence of impurities in the injection preparations. Due to the
complicated and diverse chemical composition of Chinese herbs, non-optimized manu-
facturing processes and differences in quality standards among manufacturers, the
presence of micro-particles represents a common problem in TCM-derived injection
preparations.
In China only a small number of injection preparations, like Danseng Injection, are
free from the problems of micro-particles. SMS injection is the fine-processed extracts
of Radix Ginseng Destillata, Radix Ophiopogonis and Fructus Schisandrae, with a complex
array of active ingredients, and possibly contains some macro-biomolecules like pro-
tein and polysaccharides. These varied sized micro-particles may act as hapten that can
conjugate with plasma proteins, induce allergic reactions, and hence contribute to the
development of anaphylaxis and drug-induced rash. Clinical observations also showed
that SMS injections from different manufacturers, or different batches from the same
manufacturer, may cause different rates of anaphylactic response. Therefore, upgrading
the manufacturing process and the quality standards of SMS injection preparations are
the key factors in minimizing the occurrence of side effects (Liu et al. 1999).
INTRINSIC SIDE EFFECTS
I. Dizziness, headache and insomnia

During the course of SMS treatment, a few patients have reported to have mild symp-
toms of headache, dizziness, distention of the head and insomnia. While the symptoms
usually disappeared after discontinuation of use, the side effects were not related to the
80 Zhi-Min Xu and Ye-Zhi Rong
dosage form being administered. Instead, they may be attributed to the stimulation of
the central nervous system by ginseng saponins.
II. Abdominal distension, and lumbar and back myalgia

Patients given high doses of SMS may have abdominal distension and anorexia (Zhou
and Yang 1996). According to the TCM theory of Treatment by Differentiation of Signs
and Symptoms, Ginseng is a potent Qi-invigorating herb, and its use at high doses may
cause over-invigoration of the Qi. Such over-invigoration would cause an overflow of
the liver-Qi to the stomach and an elevation of the stomach-Qi, manifested as abdominal
distension. The symptom reflects a temporary state of imbalance during the course
of treatment, and is usually relieved upon discontinuation of drug use. Furthermore,
the cause of abdominal distension may also be attributed to the cold nature of Radix
Ophiopogonis and the acidic nature of Fructus Schisandrae. Fructus Schisandrae contains
a large amount of acidic components such as malic acid, citric acid, tartaric acid
and ascorbic acid, which may cause gastric irritation. Chen (1999) reported that some
patients developed the side effects of lumbar and back myalgia, of which the cause
cannot readily be explained by modern medicine from the pathological and physio-
logical standpoints. However, the side effects may be explained by the theory of TCM
in that the over-invigoration of the Qi would cause the excessive accumulation of Qi
inside the body, resulting in muscular spasm. No particular treatment is required, and
the side effects tend to be alleviated upon discontinuation of SMS treatment or a
reduction in dosage.
III. Blood pressure elevating effects on some hypertensive patients

Clinically, SMS treatment was found to cause an elevation in the blood pressure, par-
ticularly the systolic pressure, in a small number of hypertensive patients. Given that
Radix Ginseng Destillata is able to increase myocardial contractility and the stroke
volume, failure to attenuate these effects by peripheral vasodilation may partly explain
the effect of elevated blood pressure by SMS. Furthermore, the astringent/antihidrotic
effects of Fructus Schisandrae and the Yin-nourishing effect of Radix Ophiopogonis, which
can maintain the normal vascular permeability of blood vessel and increase the
effective blood volume, may contribute to the elevation of blood pressure. These
pharmacological effects produced by Fructus Schisandrae and Radix Ophiopogonis are, in
fact, ascribable to one of the action mechanisms of SMS in treating circulatory shock.
However, such a blood pressure-elevating effect is unfavorable for patients with severe
hypertension. Hence, SMS treatment should be accompanied by antihypertensive treat-
ment when used in hypertensive patients, and should be used with caution in cases of
severe hypertension.
REFERENCES
Chen, Y.P. (1999) Report on 2 cases of back myalgia associated with SMS injection, Chinese
Journal of Hospital Pharmacy, 19(2), 127.
Hao, J., Wang, Z.A., and Dan, S.J. (1997) Report on 2 cases of allergic skin reaction associated
with the use SMS injection, Chinese Journal of Hospital Pharmacy, 17(4), 188.
Side effects 81
Liu, Y.L., Teng, L., Li, C.J., and Yu, Y.T. (1999) Unfavorable effects of Shengmai San (SMS)
injection, Yi Xue Dao Bao, 18(2), 131.
Ren, X.H. and Xia, Q. (1997) Report on a case of hypersensitivity associated with the intraven-
ous infusion of Shengmai San injection, Journal of North Sichuan Medical College, 12(1), 99.
Xin, F.B. (1999) A case of hypersensitivity associated with the use of SMS injection, Traditional
Chinese Drug Research and Clinical Pharmacology, 10(2), 115.
Xu, F.N. (1998) Report on a case of exfoliative dermatitis induced by the use SMS injection,
Journal of Anhui College of Traditional Chinese Medicine, 17(S:S), 95.
Zhou, X.L. and Yang, Y.Q. (1996) Report on 4 cases of severe stomach distention associated
with high doses of SMS injection, Forum on Traditional Chinese Medicine, 11(2), 36.
82 Siu-Po Ip et al.
5 Phytochemistry and pharmacology

of component herbs of
Shengmai San
Siu-Po Ip, Timothy C.M. Tam and
Chun-Tao Che
RADIX GINSENG
Radix Ginseng (Renshen) is the root of Panax Ginseng C. A. Mey. The root turns reddish
after steam treatment, and is known as ‘red ginseng’. It is sweet and slightly bitter in
taste. The use of Radix Ginseng has a long history in traditional Chinese medicine.
According to Shen Nong Ben Cao Jing published around 101 B. C. during the West Han
Dynasty, Ginseng was said to be able to ‘support the five visceral organs, calm the
nerves, tranquilize the mind, stop convulsions, expunge evil spirits, clear the eyes, and
improve the memory’ (Huang 1998a). The efficacy of Ginseng was known in the West
by the 18th century, and the pharmacological effects of Ginseng have been demon-
strated in the central nervous system (CNS) as well as in cardiovascular, endocrine, and
immune systems.
I. Chemical constituents of Radix Ginseng

The chemical constituents, especially saponins of Ginseng and the congeners, have been
investigated extensively. They can be classified into the following major groups.
A. Saponins
The major constituents of Ginseng are the saponins. There are three structural types of
sapogenins: oleanolic acid, 20(S)-protopanaxdiol and 20(S)-protopanaxtriol.
Component herbs 83
(1) Oleanolic acid type: ginsenoside Ro (Figure 5.1) (Sanada 1974, Li 1979)
Figure 5.1 Chemical structure of ginsenoside R0, an oleanolic acid type of saponin found
in Radix Ginseng.
(2) Protopanaxdiol type
Figure 5.2 Chemical structure of ginsenoside Rc, a protopanaxdiol found in Radix Ginseng.
84 Siu-Po Ip et al.
Several examples are listed in the Table 5.1.
Table 5.1 Protopanaxadiol-type ginsenosides from ginseng
Ginsenoside Reference
Ra1 Besso 1982a, Koizumi 1982

Ra2 Besso 1982a
Ra3 Matsuura 1984
Rb1 Kasai 1983, Sanada 1974a
Rb2 Kasai 1983, Sanada 1974a
Rb3 Kasai 1983, Sanada 1978
Rc Kasai 1983, Sanada 1974a, Luo 1983
Rd Kasai 1983, Sanada 1974a
Rg3 Kasai 1983, Sanada 1974a
Notoginsenoside R4 Matsuura 1984
Rh2 Kitagawa 1983a
Rs1 Kasai 1983
Rs2 Kasai 1983
Quinquenoside R1 Kasai 1983, Besso 1982b
Malonylginsenoside Rb1 Kitagawa 1983b
Malonylginsenoside Rb2 Kitagawa 1983b
Malonylginsenoside Rc Kitagawa 1983b
Malonylginsenoside Rd Kitagawa 1983b
(3) Protopanaxtriol type
Figure 5.3 Chemical structure of ginsenoside Rg1, a protopanaxtriol found in Radix Ginseng.
Component herbs 85
Several examples are listed in the Table 5.2.
Table 5.2 Protopanaxatriol-type ginsenosides from ginseng

Ginsenoside Reference
Re Kasai 1983, Sanada 1974b
Rf Kasai 1983, Sanada 1974b
20-Glucoginsenoside Rf Kasai 1983, Sanada 1978
Rg1 Kasai 1983, Iida 1968, Nagai 1971
Rg2 Kasai 1983, Sanada 1974b
20 (R) Rg2 Kitagawa 1983a
Notoginsenoside R1 Kasai 1983
Rh1 Kitagawa 1983a
B. Volatile components
Ginseng was found to contain a lot of volatile components including a series of sesquiter-
penes such as eremphilene, β-gurjunene, trans- and cis-caryophyllene, ε-muurolene, γ-
patchoulene, β-eudesmol, β-farnesene, β-bisabolene, aromadendrene, alloaromadendrene,
β-guaiene, γ-elemene, mayurone, pentadecane, 2,5-dimethyltridecane, and palmitic
acid (Zhang 1985).
C. Polysaccharides
The polysaccharide preparation of Ginseng containing 89 per cent sugars and 5 per
cent proteins. The polysaccharide fraction is composed of 80 per cent starch and 20
per cent pectin. The protein fraction contained 15 amino acids such as leucine and
arginine (Li 1985).
D. Acetylenic compounds
Panaxynol (Takahashi 1966a; Takahashi 1966b), panaxydol (Poplawski 1980), pana-
xytriol (Shim 1983), and heptadeca-1-ene-4,6-diyn-3,9-diol were isolated and identified
(Dabrowski 1980).
E. Peptide glycans
Isolation of panaxans A, B, C, D, E (Konno 1984), F, G, H (Hikino 1985), I, J, K, L
(Oshima 1985), Q, R, S, T, and U (Konno 1985) has been reported.
F. Sugars
Ginseng contains a sugar fraction, which comprises two monosaccharides, D-glucose
and D-fructose, two disaccharides, sucrose and maltose, and three trisaccharides,
maltosyl-β-D-fructofuranose, O-α-D-glucopyranosyl(1→2)-O-β-D-fructofuranosyl(1→
2)-β-D-fructofuranose, and O-α-D-glucopyranosyl(1→6)-O-α-D-glucopyranosyl(1→4)-
α-D-glucopyranose (Shoji 1985).
86 Siu-Po Ip et al.
G. Others
Besides saponins, Ginseng also contains β-sitosterol (Xu 1988), stigmasterol, daucosterol
(Lu 1985), campesterol, salicymide (Zhang 1989), adenosine, dencichine, and maltol.
II. Pharmacology of Radix Ginseng
A. Effects on CNS
Ginsenosides, the saponins of Ginseng, are active ingredients which exert many bio-
logical effects. They have both stimulatory and inhibitory effects on the CNS. It has
been reported that intraperitoneal administration of Ginseng total saponins not only
inhibited hyperactivity and reverse tolerance, but also suppressed postsynaptic dopamine
receptor supersensitivity induced by administration of cocaine or nicotine (Kim et al.
1995; Kim and Kim 1999).
It was suggested that the learning and memory processes are mediated by the central
cholinergic systems. Ginsenosides Rb1 and Rg1 have been shown to prevent scopolamine-
induced memory deficits in rats by facilitating acetylcholine release from rat brain
hippocampal slices and increasing cholinergic activity (Benishin et al. 1992; Yamaguchi
et al. 1995). Intraperitoneal administration of ginsenoside Rg1 at a dose of 10 mg/kg to
rats enhanced the discrimination between two sounds. It also stimulated the exploratory
behavior in rats (Shibata et al. 1985). Recently, Lee et al. (2000) showed that repeated
administration of Ginseng total saponins ameliorated the impairing effect of ethanol on
acquisition, and the effect of the saponins on ethanol-induced amnesia was dependent
on the catecholaminergic, but not serotonergic, neuronal activity. Intraperitoneal admin-
istration of Ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol
saponin at doses of 50 and 100 mg/kg respectively, also improved scopolamine-
induced learning disability and spatial working memory in mice (Jin et al. 1999).
Ginsenosides pretreatment may also prevent ischemic damage to neurons. It has been
demonstrated that intracerebroventricular infusion of ginsenoside Rb1, prior to transient
forebrain ischemia, precluded significantly ischemia-induced shortening of response
latency in a step-down passive avoidance task, and rescued a significant number of
hippocampal CA1 neurons from lethal damage (Lim et al. 1997; Wen et al. 1996).
Ginsenosides may modulate nerve transmission by altering the availability of neuro-
transmitters. It has been shown that Ginseng extract inhibited the uptake of GABA,
glutamate, dopamine, noradrenaline, and serotonin in rat brain synaptosomes (Tsang
et al. 1985). Kimura et al. (1994) also demonstrated that ginsenosides Rb1, Rb2, Rc,
Re, Rf, and Rg1 competed with agonists for binding to GABA receptors.
B. Immunomodulatory effects
Yun et al. (1987) reported that administration of Ginseng prevented the depression of
natural killer (NK) cell activity induced by injection of carcinogens. The incidence
of lung adenoma was lowered following the administration of Ginseng in urethane-
injected mice. A systematic evaluation of multiple immune system components revealed
that Ginseng stimulated basal NK cell activity following subchronic exposure and
enhanced the recovery of NK function in cyclophosphamide-immunosuppressed mice,
but did not further stimulate NK activity in poly I:C treated mice (Kim et al. 1990).
Component herbs 87
The same treatment provided a degree of protection against infection with monocytes,
but did not inhibit the growth of transplanted syngeneic tumor cells. Kenarova et al.
(1990) reported that administration of ginsenoside Rg1 at a dose of 10 mg/kg for three
consecutive days before immunization increased the number of spleen plaque-forming
cells, the titers of sera hemagglutinins, as well as the number of antigen-reactive T-
cells. Ginsenoside Rg1 also increased the number of T-helper cells with respect to the
whole T-cell number and the splenocyte natural killer activity. Ginsenoside Rg1 induced
an augmentation of the production of IL-1 by macrophages, and exerted a direct
mitogenic effect on microcultured thymus cells. Ginsenoside Rg1 also partly restored
the impaired immune reactivity by cyclophosphamide treatment. Ginseng extract at
a concentration of 10 mg/kg significantly enhanced NK-function in peripheral blood
mononuclear cells from normal individuals and patients with either chronic fatigue
syndrome or acquired immunodeficiency syndrome (Odashima et al. 1985).
C. Cardiovascular effects
The cardiovascular effects of Ginseng have been studied extensively. Various preparations
and concentrations of Ginseng have been reported with diverse effects, including the
influence on platelet aggregation, and transient vasodilation, in some cases followed by
vasoconstriction. It appears that Ginseng has both hypotensive and hypertensive effects.
The discrepancies of the studies may be due to the difference in manufacturing processes
or ginsenoside content of the extracts used. Lee et al. (1981) have reported the effect of
various extracts of Korean Ginseng on cardiovascular function in dogs. Each extract at
a dose of 40 mg/kg was administered intravenously to ten dogs under light halothane
anesthesia. The administration of ether extract caused a significant decrease in heart rate
and central venous pressure. The same treatment regimen with ethanol extract caused
a significant decrease in the heart rate and mean arterial pressure. Following the admin-
istration of the aqueous extract, the cardiac output, stroke volume, and central venous
pressure were significantly decreased, while the total peripheral resistance was signific-
antly increased (Lee et al. 1981). The cardiovascular function of Ginseng appears to be
related to its ability to block α-receptors, leading to vasodilation and catecholamine
release. However, Gillis (1997) questioned whether some of these complex vascular
effects might reflect the qualitative and quantitative heterogeneity of ginsenoside action
on different vascular beds that could also be observed in vitro. Total Ginseng root extract
did not alter basal vascular tone of vessels from rabbits, dogs, and humans, but relaxed
those vessels that were pre-contracted with either norepinephrine or prostaglandin F2α.
The author therefore suggested that these actions could reflect the interaction of Ginseng
with an endogenous vasoactive substance which appeared to be nitric oxide (Gillis 1997).
Recently, Maffei Facino et al. (1999) showed that oral administration of Ginseng extract
at a daily dose of 1.6 g/kg for one week prevented the myocardial ischemia/reperfusion
damage and the impairment of endothelial functionality induced by reactive oxygen
species arising from hyperbaric oxygen exposure. The in vitro radical scavenging activity
of the Ginseng extract seemed to be too weak to explain by itself the cardiac and extra-
cardiac protective effects. Therefore, the author suggested that the protective effect of
Ginseng extract was mediated by the stimulation of endothelial nitric oxide synthase,
an indirect antioxidant action of the drug (Maffei Facino et al. 1999).
Beside the action on blood pressure, the effect of Ginseng on platelet aggregation has
been reported. Matsuda et al. (1986a) showed that ginsenoside Rg2 strongly inhibited
88 Siu-Po Ip et al.
platelet aggregation induced by aggregating agents. Ginsenoside Rg2 also inhibited
the conversion of fibrinogen to fibrin induced by thrombin. Another study by Matsuda
et al. (1986b) showed that ginsenoside Ro prevented disseminated intravascular coagula-
tion induced by infusion of endotoxin or thrombin in rats. Ginsenoside Ro also inhibited
the formation of fibrin thrombi in the renal glomeruli in thrombin-induced dis-
seminated intravascular coagulation. The effect of Ginseng saponins on aggregation and
5-hydroxytryptamine (5-HT) release with human platelets was reported by Kimura
et al. (1988). Among the six saponins tested, only ginsenoside Rg1 inhibited adrenaline-
and thrombin-induced platelet aggregation and 5-HT release dose-dependently, at
concentrations of 5 to 500 mg/ml. Ginsenoside Rg1 had no effect on adrenaline- and
thrombin-induced arachidonic acid release and diacylglycerol production. However,
it did reduce the elevation of cytosolic free calcium concentration shown in the second
phase induced by adrenaline and thrombin, at concentrations ranging from 10 to
500 mg/ml, respectively (Kimura et al. 1988). The authors therefore suggested that
the inhibitory effects of ginsenoside Rg1 on 5-HT release and aggregation of platelets
may be due to the reduction of free calcium elevation at the second phase induced by
adrenaline and thrombin. A comparative study on the anti-platelet effect of panaxynol
isolated from diethyl ether layer of Ginseng extract with those ginsenosides from the
butanol layer, showed that panaxynol was the most potent anti-platelet agent in
Ginseng, and its mechanism of action was mainly due to the inhibition of thromboxane
formation (Teng et al. 1989).
D. Hematopoietic effects
The stimulatory effect of Ginseng on the hematopoietic function of the bone marrow has
been demonstrated by monitoring the levels of blood cells and hemoglobin in normal
and anemic animals. An in vitro study showed that total saponins of Ginseng enhanced
the proliferation of progenitor cells from normal individuals (Gao et al. 1992). The
cell number in bone marrow culture of BFU-E, CFU-E, and CFU-GM was increased
by 37.8, 31.4, and 33.3 per cent respectively. The Ginseng saponins were also effective
in bone marrow culture from some patients with aplastic anemia who are sensitive to
methyltestosterone, but not in culture from patients with immune-mediated and stem
cell-decreased aplastic anemia.
E. Effects on endocrine system

Among the diverse effects of Ginseng, endocrine effect is the most clear-cut, particularly
the stimulatory effect on the hypothalamopituitary suprarenal cortical system (Huang
1998a). Administration of Ginseng to rats decreased the vitamin C level of the adrenal
cortex, but this effect was not observed in hypophysectomized animals. It was shown
that the decrease of vitamin C was mediated by the stimulatory effect of adrenal-
corticotropic hormone (ACTH) on the pituitary gland. The action of Ginseng on the
adrenal cortex was corroborated by the study of Luo et al. (1993). Intragastrical or
intraperitoneal administration of ginsenoside Rb1 to mice under swim stress at a dose
of 10 mg/kg, completely antagonized the immunosuppression induced by swim stress,
and further increased the level of serum corticosterone in the mice. Fulder (1981) also
showed that the binding of corticosteroid to certain brain regions was increased in
adrenalectomized rats treated with Ginseng saponin.
Component herbs 89
Ginseng has been reported to reduce blood sugar levels in normal and alloxan-
induced hyperglycemic mice by increasing hepatic lipogenesis and glycogen storage
(Oshima et al. 1985). Sotaniemi et al. (1995) suggested that Ginseng may be a useful
therapeutic adjunct in the management of non-insulin-dependent diabetes mellitus
(NIDDM) patients. Treating 36 NIDDM patients with Ginseng at a daily dose of
200 mg/person for 8 weeks improved mood and psychophysical performance in diabetic
patients. It also led to beneficial changes in daily life, habits, and diet, as indicated
by increased physical activity and reduced body weight. Fasting blood glucose was
reduced, and glucose response to an oral glucose tolerance test was improved, a reflec-
tion of good glycemic control as evidenced by a decrease in glycosylated hemoglobin
(Sotaniemi et al. 1995).
However, contradictory results have been reported on the effect of Ginseng on sexual
development. Early studies showed that administration of Ginseng extract to castrated
mice would neither prevent the atrophy of the male prostate and seminal vesicles
nor promote pubertal development in female mice (Huang 1998a). However, other
studies with young rodents showed that Ginseng extract produced a stimulatory effect
on sexual function. Such stimulation was not observed in hypophysectomized rats.
It implied that the action of Ginseng on the sex organs was mediated by a stimulation
of the hypothalamopituitary axis through increasing the secretion of gonadotropins
(Huang 1998a).
With an in vitro tissue superfusion technique, Chen and Lee (1995) demonstrated
that ginsenosides at concentrations ranging from 250 to 750 mg/ml caused a dose-
dependent relaxation of corpus cavernosum. Acetylcholine-induced relaxation was
increased in the presence of ginsenosides at a concentration of 250 mg/ml. Ginsenosides
at 100 mg/ml significantly enhanced the tetrodotoxin-sensitive relaxation of corpus
cavernosum elicited by transmural nerve stimulation. The authors suggested that
ginsenosides may cause the release of nitric oxide from endothelial cells, and enhance
nitric oxide release from endothelial cells elicited by other vasoactive substances and
from perivascular nitrergic nerves in the corpus cavernosum (Chen and Lee 1995).
A recent study showed that long-term administration of Ginseng in rabbits enhanced
erectile capacity that was mediated by endothelium-derived relaxing factor and peri-
pheral neurophysiologic enhancement (Choi et al. 1999).
F. Effect on metabolism
(1) Carbohydrate metabolism

Ginseng is used in Chinese medicine to reduce blood sugar level in diabetic pati-
ents. Ginseng polypeptide isolated from the root of Panax ginseng has been found to
decrease the level of blood sugar and liver glycogen when injected intravenously
to rats at doses of 50–200 mg/kg (Wang et al. 1990). The polysaccharides increased
the content of pyruvic acid, but decreased the content of lactic acid by decreasing the
activity of lactate dehydrogenase in the liver. Ginseng polysaccharides also acceler-
ated oxidative phosphorylation of carbohydrate by the enhancement of succinate
dehydrogenase and cytochrome oxidase activities (Yang et al. 1990). Recently, Onomura
et al. (1999) found that Ginseng treatment inhibited absorption of glucose or maltose
in rat and human duodenal mucosa, and at the same time increased duodenal muscle
movement.
90 Siu-Po Ip et al.
(2) Lipid metabolism
It has been reported that treating rats intraperitoneally with ginsenosides Rc at
50 mg/kg increased epididymal synthesis of fat and intestinal fat synthesis by three-
and six-fold respectively, in rats pretreated with acetic acid. Many ginsenosides, such
as Rb1, Rb2, Rc, Rd, Re, Rg1, Rg2 and Rh1 have been shown to be able to antagonize the
lipolytic effects of ACTH or insulin. Several studies have showed that oral administra-
tion of ginsenosides would significantly reduce the level of cholesterol in plasma and
liver. Yang et al. have demonstrated that ginsenoside treatment combined with aerobic
exercise could lower serum cholesterol and triglycerides in diet-induced hyperlipidemia
mice (Yang et al. 1999).
(3) RNA and DNA metabolism

It has been reported that Ginseng treatment could increase serum proteins by enhanc-
ing RNA biosynthesis and incorporating amino acids into the nuclei of hepatic and
renal cells. An intraperitoneal injection of ginsenosides Rb2, Rc, Re and Rg at doses
from 5 to 10 mg/kg increased DNA synthesis in bone marrow cells. RNA, protein and
lipid synthesis were also increased. The direct addition of a mixture of ginsenosides
(Rb1, Rb2 and Rc) also enhanced DNA synthesis (Yamamoto et al. 1978).
G. Antineoplastic effects
In vitro and in vivo studies have suggested that Ginseng may prevent or ameliorate
various cancers. Yun (1996, 1999) reported that prolonged administration of red Ginseng
extract inhibited the incidence of tumors induced by 9,10-dimethyl-1,2-benzanthracene,
urethane, and aflatoxin B1. Recent investigation showed that red Ginseng extract at
50–400 mg/kg could inhibit 7,12-dimethyl benez[a] anthracene-induced skin papilloma
in mice, decrease the incidence of papilloma, prolong the latent period of tumor occur-
rence, and reduce tumor number per mouse in a dose-dependent manner (Xiaoguang
et al. 1998).
Some studies showed that ginsenosides showed direct cytotoxic and growth inhibitory
effects against tumor cells (Wakabayashi et al. 1998; Atopkina et al. 1999; Lee et al.
1999; Liu 2000). Liu et al. (2000) showed that ginsenoside Rg3 activated the expression
of cyclin-kinase inhibitors, p21 and p27, arrested LNCaP cells at G1 phase, and sub-
sequently inhibited cell growth through a caspase-3-mediated apoptosis mechanism.
A similar study showed that the cytotoxic effect of ginsenoside Rh2 in B16 melanoma
cells was mediated by the induction of G1 arrest and concomitant suppression of
cyclin-dependent kinase-2 activity (Moon et al. 2000). Several studies have reported
the anti-metastatic effect of ginsenosides (Mochizuhk et al. 1995; Wakabayashi et al.
1998). Wakabayashi et al. (1997) showed that the in vivo anti-metastatic effect in-
duced by oral administration of Ginseng protopanaxadiol saponins was mediated by
their metabolic component M1, and that the growth, invasion and migration of tumor
cells were inhibited by M1, but not by ginsenosides. Their further investigations
demonstrated that the M1 induced apoptotic cell death in B16 melanoma cells by up-
regulating the expression of p27Kip1 and down-regulating the expression of c-Myc
and cyclin D1 (Wakabayashi et al. 1998). Study of Mochizuki et al. (1995) showed
that two saponin preparations from red Ginseng, 20(R)- and 20 (S)-ginsenoside-Rg3,
Component herbs 91
inhibited lung metastasis produced by B16-BL6 melanoma and colon 26-M3.1 car-
cinoma in syngeneic mice, and suggested that the anti-metastatic effect of the two
saponins was related to inhibition of the adhesion and invasion of tumor cells and anti-
angiogenesis activity.
H. Antioxidant activities
Oxygen-derived reactive species play an important role in many human diseases such
as ischemia/reperfusion injury in the heart. Since Ginseng is an important component
of Shengmai San that is used for the treatment of myocardial diseases, many studies
attributed the myocardial protective effect of Ginseng to its antioxidant activities (Mei
et al. 1994; Liu et al. 1998; Maffei Facino et al. 1999). Liu et al. (1998) have demon-
strated that after global ischemia for 60 minutes followed by 30 minutes of reperfusion
in a transplanted heart, superoxide dismutase activity in the myocardium treated with
ginsenosides was significantly enhanced when compared with the control group. The
levels of oxygen free radicals and malondialdehyde, an index of lipid peroxidation,
were markedly decreased in the myocardium treated with ginsenosides (Liu et al.
1998). Recent studies suggested that Ginseng prevented myocardial ischemia/reperfusion
injury by an indirect antioxidant action of the drug through the stimulation of
endothelial nitric oxide synthase and the subsequent prevention of reactive oxygen
species-induced impairment of the endothelial functionality (Mei et al. 1994; Maffei
Facino et al. 1999).
Besides, some studies have reported the in vivo and in vitro antioxidant activity of
Ginseng in other tissues (Zhong and Jiang 1997; Voces et al. 1999; Keum et al. 2000).
Voces et al. (1999) showed that prolonged treatment with a standardized Ginseng extract
significantly increased the hepatic glutathione peroxidase activity and the levels of
glutathione in the liver, with a dose-dependent reduction of the thiobarbituric acid
reactive substances (TBARS, an indirect index of lipid peroxidation). Zhang et al.
(1997) have demonstrated that Ginseng extract directly inhibited the decomposition of
unsaturated fatty acids caused by iron and hydrogen peroxide-induced lipid peroxida-
tion. A recent study reported that heat treatment of Ginseng at a temperature higher
than that applied to the conventional preparation of red Ginseng yielded a mixture
of saponins with potent antioxidative properties (Keum et al. 2000). The methanol
extract of this ‘neoginseng’ attenuated lipid peroxidation in rat brain homogenates
induced by ferric ion or ferric ion supplemented with ascorbic acid. The extract pro-
tected against strand scission in phiX174 supercoiled DNA induced by UV photolysis
of H2O2, and was also capable of scavenging superoxide generated by xanthine-xanthine
oxidase or by 12-O-tetradecanoylphorbol-13-acetate in differentiated human promyelo-
cytic leukemia cells (Keum et al. 2000).
I. Adaptogenic effects
The term adaptogen was used to describe the non-specific ‘tonic’ effect of a substance
(Brekhman and Dardymov 1969). Ginseng has been used for several thousand years
as a tonic, prophylactic agent, and a ‘restorative’; it is also used by athletes as an
ergogenic and anti-fatigue agent (Bahrke and Morgan 1994). D’Angelo et al. (1986)
reported that healthy male volunteers, given a standardized preparation of Korean
Ginseng for 12 weeks, showed better performance in certain psychomotor functions. A
92 Siu-Po Ip et al.
double-blind, randomized, crossover study in 50 healthy male sports teachers showed
that Ginseng preparation increased the subjects’ work capacity by improving muscular
oxygen utilization (Pieralisi et al. 1991). At the same workload, oxygen consumption,
plasma lactate levels, ventilation, carbon dioxide production, and heart rate were
decreased in subjects receiving Ginseng treatment (Pieralisi et al. 1991). The adaptogenic
actions of Ginseng were more obvious when the tested subject was under stressful
conditions (Bahrke and Morgan 1994). Recent study showed that Ginseng treatment
improved psychomotor performance at rest and during graded exercise in young
athletes, as indicated by a shortening of reaction time to multiple-choice questions
(Ziemba et al. 1999).
The adaptogenic effects of Ginseng have been attributed to the increase in
hypothalamic-pituitary-adrenal sensitivity (Fulder 1981). It has been reported that an
intraperitoneal injection of Ginseng increased plasma immunoreactive adrenocorticotropic
hormone and corticosterone in rats, and the effects were abrogated by hypophysectomy
(Hiai et al. 1983). Besides, some studies attributed the adaptogenic effects of Ginseng
to its action on the CNS (Bhattacharya and Mitra 1991; Kim et al. 1992).
J. Pharmacokinetics
Following an oral administration of [3H]ginsenoside Rg1, the bioavailability of the
ginsenoside in the blood was 49 per cent and peaked at 2.1 hours (Liu and Xiao 1992).
After an intravenous injection of [3H]ginsenoside Rg1 in mice, the radioactivity decreased
in a triphasic manner in the blood, and the distribution of radioactivity in tissues
followed a decreasing order of kidney, adrenal gland, liver, lungs, spleen, pancreas, heart,
testes, and brain (Liu and Xiao 1992). After administration of ginsenoside Rg1 in rats,
only trace amounts of ginsenosides were excreted in the urine (Odani et al. 1983).
Using GC-MS to analyze urine samples of 65 athletes who had ingested Ginseng for
10 days prior to urine collection, an aglycone of ginsenosides, 20(S) protopanaxatriol,
was detected at a concentration of between 2 and 35 ng/ml in 90 per cent of the samples
(Cui et al. 1996).
K. Toxicity
The LD50 of Ginseng root in mice was reported to be 10 to 30 g/kg (Gillis 1997).
Tam (1992) showed that the LD50 values of purified Ginseng saponins in male mice
were 270 mg/kg (intravenous injection), 342 mg/kg (intraperitoneal injection),
505 mg/kg (intramuscular injection), 950 mg/kg (subcutaneous injection), and 5 g/kg
(oral administration). Clinical study on patients using 3 per cent Ginseng tincture
up to 100 ml showed slight irritation and excitation. When the dose was doubled,
urticaria, itching, headache, dizziness, hemorrhage, and insomnia were observed (Huang
1998a).
FRUCTUS SCHISANDRAE
Fructus Schisandrae (Wuweizi) is the fruit of Schisandra chinensis (Turcz.) Baill. or

Schisandrae sphenanthera Rehd et Wils. The fruit has a sweet and sour taste and is used
Component herbs 93
as a tonic and sedative in traditional Chinese medicine. Starting from the 1950s,
pharmacological effects of Fructus Schisandrae on the central nervous system and the
cardiorespiratory function have been reported. At the beginning of 1970s, the herb
was used clinically for the treatment of chronic viral and chemical hepatitis.
I. Chemical constituents of Fructus Schisandrae

A series of compounds have been isolated from Fructus Schisandrae, and they can be
classified into the following types.
A. Volatile components
Fructus Schisandrae was found to contain a lot of volatile components including α- and
β-pinene, camphene, myrcene, limonene, α-terpinene, γ-terpiene, p-cymene, thymol
methylether, bornyl acetate, citronellyl acetate, linalool, terpinen-4-ol, geraniol, borneol,
cuparene, and chanigrenol (Ohta 1968a; Ohta 1968b).
B. Lignans
A series of lignans of the dibenzo[a,c]cyclooctadiene type have been isolated from
Schisandra species, some of which showed significant biological and biochemical activities
in experimental and clinical studies. Lignans are plant phenols whose structure is
represented by the union of two cinnanmic acid residues or their biogenetic equivalents.
The first compound of the dibenzo[a,c]cyclooctadiene type (Figure 5.4) isolated from
seed oil of Schisandra chinensis was schisandrin. Selected examples of reported compounds
in Fructus Schisandrae are shown in the Table 5.3.
Several lignans derivatives other than dibenzo[a,c]cyclooctadiene were also isolated
such as pregomisin (Figure 5.4) (Ikeya 1978b).
Figure 5.4 Chemical structures of constituents derived from dibenzo[a,c]cyclooctadiene in

Fructus Schisandrae.
94 Siu-Po Ip et al.
Table 5.3 Lignans reported from Wuweizi
Compound Reference
Schisandrin A Song 1983, Chen 1976
Schisandrin B Song 1983, Chen 1976, Ikeya 1982a, Tan 1986
Schisandrin C Song 1983, Chen 1976, Ikeya 1982b
Schisandrol A Kotchetkov 1961, Ikeya 1979a
Schisandrol B Ikeya 1979a, Taguchi 1975, Taguchi 1977
Schisantherin A Ikeya 1979a, Taguchi 1975, Taguchi 1977
Schisantherin B Ikeya 1979a, Taguchi 1975, Taguchi 1977
Isoschisandrin Ikeya 1988a
Gomisin D Ikeya 1976, Ikeya 1979b
Gomisin E Ikeya 1979c
Gomisin F Ikeya 1979a
Gomisin G Ikeya 1979a
Gomisin H Ikeya 1979d
Angeloylgomisin H Ikeya 1979d, Ikeya 1978a
Benzoylgomisin H Ikeya 1979d, Ikeya 1978a
Tigloylgomisin H Ikeya 1979d, Ikeya 1978a
Gomisin J Ikeya 1978b, Ikeya 1979e
Gomisin K1 Ikeya 1980a
Gomisin K2 Ikeya 1980a
Gomisin K3 Ikeya 1980a, Liu 1985
Gomisin L1 Ikeya 1982a
Gomisin L2 Ikeya 1982a
Gomisin M1 Ikeya 1982a
Gomisin M2 Ikeya 1982a
Gomisin N Ikeya 1978c, Hikino 1984
Gomisin O Ikeya 1979c
Angeloylgomisin O Ikeya 1982c
Benzoylisogomisin O Ikeya 1982c
Angeloylisogomisin O Ikeya 1982c
Epigomisin O Ikeya 1979c
Angeloylgomisin P Ikeya 1980b
Trgloylgomisin P Ikeya 1978a, Ikeya 1980b
Angeloylgomisin Q Ikeya 1979f
Gomisin R Ikeya 1982b
Gomisin S Ikeya 1988b
Gomisin T Ikeya 1988b
Deoxygomisin A Hikino 1984
C. Glycosides
Thymoquinol-5-O-β-D-glucopyranoside, thymoquinol-2-O-β-D-glucopyranoside, and
kaempferol-3-O-β-ruutinoside were isolated (Yahara 1993).
D. Others
Besides lignans and glycosides, Fructus Schisandrae was also found to contain citral,
chlorophyll, protocatechuic acid and vitamin C and E (Yahara 1993).
Component herbs 95
II. Pharmacology of Fructus Schisandrae
A. Effects on CNS
Different components isolated from Schisandra chinensis have been shown to have a
contradictory effect on the CNS. Fructus Schisandrae had a stimulatory action in
strengthening the spinal reflex and reducing the reflex latency. Volatile oil from Fructus
Schisandrae could reduce the sleeping time induced by pentobarbital. However, the
ethanol extract and the isolated schisandrins significantly prolonged the sleeping time
(Niu et al. 1983; Song et al. 1990). This action has been attributed to the inhibition
of microsomal enzymes in the liver.
It has been shown that an intraperitoneal injection of schisandrol A at a dose of
11 mg/kg (1/50 of LD50) decreased spontaneous motor activity in mice. The treatment
also enhanced the inhibitory effects of chlorpromazine, reserpine and pentobarbital,
and antagonized the stimulating effects of amphetamine and caffeine on spontaneous
motor activity in mice (Niu et al. 1983). Besides, Song et al. reported that schisandrin
and daucosterol isolated from a methanol extract of Schisandra chinensis could elevate the
neurotransmitter GABA level in the CNS by inhibiting GABA-degradative enzymes.
B. Cardiovascular effects
The extract of the herb has been reported to induce vasodilation and hypotension in
humans and animals. However, the extract increased blood pressure under circulatory
failure, and thus it might produce a regulatory effect on blood pressure (Zhu 1998b).
A recent study showed that treating rats with schisandrin B at doses of 0.6 and
1.2 mmol/kg for three days protected against myocardial ischemia-reperfusion injury
in a dose-dependent manner (Yim and Ko 1999). The myocardial protection was
associated with an enhancement in myocardial glutathione antioxidant status, as indic-
ated by significant reductions in glutathione depletion and inhibition of Se-glutathione
peroxidase and glutathione reductase activities induced by ischemia-reperfusion in
isolated hearts (Yim and Ko 1999).
C. Hepatoprotective effect
The hepatoprotective effect is the most important action of Schisandra chinensis. Pretreat-
ing experimental animals with the extracts or lignans isolated from the herb protected
against hepatic injury induced by a variety of chemical and immunological toxins, as
indicated by the significant decreases of plasma alanine aminotransferase activity and
necrosis of hepatocytes (Nagai et al. 1989; Lu and Liu 1991; Mizoguchi et al. 1991a,
1991b; Yamada et al. 1993). The hepatoprotection was at least in part attributed
to the induction of hepatic cytochrome P-450 dependent enzymes and glutathione
S-transferases for the detoxification reactions. In addition, the ability to inhibit lipid
peroxidation under oxidative stress may also contribute to the hepatoprotective action
of the lignans against free-radical mediated damage in the liver (Liu et al. 1992; Lu
and Liu 1992; Zhang et al. 1992).
The lignans have been found to enhance the proliferation of endoplasmic reticulum
and induce hypertrophy in the liver. The syntheses of hepatic proteins and microsomal
cytochrome P-450 content were also increased by treating animals with the lignans
96 Siu-Po Ip et al.
(Liu et al. 1980; Liu et al. 1981). Oral administration of gomisin A, a lignan com-
ponent of Fructus Schisandrae, enhanced liver functions, as indicated by the increases
in bile secretion and hepatic secretion of bromosulfophthalein, presumably through
the increase of liver blood flow (Takeda et al. 1988). It has been demonstrated that
treating rats with gomisin A accelerated both the proliferation of hepatocytes and the
recovery of liver function after partial hepatectomy (Takeda et al. 1986). An oral
administration of gomisin A to rats 30 minutes before partial hepatectomy signific-
antly increased the mitotic index and the level of DNA synthesis. The treatment
stimulated liver regeneration after partial hepatectomy by enhancing ornithine decar-
boxylase activity, which is an important biochemical event in the early stages of liver
regeneration (Kubo et al. 1992).
D. Antioxidant activities
Free radical scavenging activity of the lignans isolated from Fructus Schisandrae has
been extensively investigated in a number of in vitro assay systems using microsomes,
mitochondria, and homogenate prepared from liver, brain, heart, and kidney (Lin et al.
1991; Liu et al. 1992; Lu and Liu 1992; Zhang et al. 1992). The scavenging activity
was demonstrated either directly by using electron magnetic resonance measurement
of free radicals (Li et al. 1990; Lin et al. 1990) or indirectly by measuring the forma-
tion of malondialdehyde and the membrane integrity (Zhang et al. 1989). In all cases,
the lignans were found to be more potent than vitamin E in the inhibition of lipid
peroxidation (Lin et al. 1990).
However, the antioxidant potential of Fructus Schisandrae is found to be mainly due
to its modulation on in vivo antioxidant mechanisms as implicated in animal studies
(Ko et al. 1995; Ip et al. 1995, 1996, 1997; Ip and Ko 1996). In a study examining
the effect of the herb on hepatic glutathione status, it was shown that treating rats
with a petroleum ether extract of Fructus Schisandrae for three days caused a dose-
dependent enhancement on hepatic glutathione status, as indicated by increases in
hepatic glutathione level and activities of hepatic glutathione reductase and glucose-6-
phosphate dehydrogenase (Ko et al. 1995). The treatment also decreased the susceptib-
ility of liver homogenate to glutathione depletion induced by t-butylhydroperoxide.
The enhancement in hepatic glutathione status has been ascribed to the decreases
of cellular damage and lipid peroxidation in liver of carbon tetrachloride (CCl4)-
treated rats, as assessed by plasma activity of alanine aminotransferase and hepatic
level of malondialdehyde, respectively (Ko et al. 1995a). The results suggested that the
hepatoprotective effect of the lignoid extract may involve the facilitation of glutathione
regeneration catalyzed by glutathione reductase. A subsequent study showed that
pretreating rats with the lignoid extract caused a significant enhancement of hepatic
glutathione regeneration capacity in CCl4-treated animals (Ko et al.1995b).
Using an animal model of CCl4-induced hepatotoxicity, the activity-directed
fractionation of the extract of Fructus Schisandrae has led to the isolation of schisandrin
B as the major active component (Ip et al. 1995). Schisandrin B pretreatment caused a
dose-dependent protection against CCl4-induced hepatocellular damage. Schisandrin B
treatment caused linear increases in activities of hepatic glutathione-S-transferase and
glutathione reductase (Ip et al. 1995). A subsequent study found that schisandrin B
protected against CCl4 hepatotoxicity by enhancing the mitochondrial glutathione
redox status in mouse liver (Ip et al. 1996). A comparative study between schisandrin
Component herbs 97
B and butylated hydroxytoluene, a synthetic phenolic antioxidant, suggested that the
ability to sustain the hepatic mitochondrial glutathione level and the hepatic ascorbic
acid and α-tocopherol levels may represent a crucial antioxidant action of schisandrin
B in protecting against CCl4-induced hepatocellular damage (Ip and Ko 1996). A
study using schisandrins A, B and C on CCl4 toxicity showed that the methylenedioxy
group of the lignan molecule was an important structural determinant in enhancing
hepatic mitochondrial glutathione status particularly under oxidative stress (Ip et al.
1997).
E. Anticarcinogenic effects
The lignans isolated from Fructus Schisandrae were found to be able to inhibit tumor
formation induced by chemical carcinogens. The mutagenic and oncogenic effects of
carcinogens require metabolic activation to their ultimate forms by microsomal cyto-
chrome P-450 associated monooxygenases. An in vitro study showed that several lignans
from the herb inhibited hepatic microsomal hydroxylation of benzo[a]pyrene and
demethylation of aminopyrine (Liu and Lesca 1982). Schisandrin B and schizandrol B
also decreased mutagenicity of benzo[a]pyrene in an Ames test.
Yasukawa et al. (1992) showed that gomisin A, gomisin J, and schisandrin C
inhibited the inflammatory activity induced by 12-O-tetradecanoylphorbol-13-acetate
in mice. In addition, treating mice with gomisin A at a dose of 5 µmol/mouse
markedly suppressed the promotion effect of 12-O-tetradecanoylphorbol-13-acetate on
skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene.
It was suggested that the inhibition of tumor promotion by gomisin A was due to its
anti-inflammatory activity (Yasukawa et al. 1992). Another study by Ohtaki et al.
(1994) showed that gomisin A inhibited the increases of glutathione S-transferase
placental form (a marker enzyme of preneoplasm) induced by 3′-methyl-4-
dimethylaminoazobenzene (3′-MeDAB) in rats. It also reduced the population of
diploid nuclei (a proliferative state of hepatocytes) in the liver of 3′-MeDAB-treated
rats. The authors suggested that gomisin A inhibited the hepatocarcinogenesis induced
by 3′-MeDAB through an enhancement of the excretion of the carcinogen from the
liver and reversing the normal cytokinesis (Ohtaki et al. 1994).
F. Effects on physical exercise

Like Ginseng, Schisandra chinensis has been used as an adaptogen which can counteract
fatigue and improve physical performance. Treating Polo horses with an ethanol extract
of Fructus Schisandrae reduced the increase of heart rate induced by exercise (Ahumada
et al. 1989). After the race, the horses treated with the extract showed a quick recovery
of respiratory frequency and a significant reduction of the concentration of lactate
in plasma. The horses treated with the extract also showed better performance in
the race. A similar study showed that treating race and spring horses with an ethanol
extract of Fructus Schisandrae at a single dose of 12 g 30 minutes prior to exercise
reduced heart rate and respiratory frequency of the horses at different time intervals
after the race (Hancke et al. 1994). The beneficial effect of the extract was suggested to
be mediated by facilitating the recuperation of cardiovascular, respiratory and meta-
bolic systems in horses subjected to different kinds of exercise. A treadmill running
study showed that pretreating rats with a lignan-enriched extract of Fructus Schisandrae
98 Siu-Po Ip et al.
protected against physical exercise-induced muscle damage (Ko et al. 1996). Interest-
ingly, the muscle protection afforded by Fructus Schisandrae pretreatment was associated
with a significant enhancement in hepatic antioxidant status, as assessed by the levels
of glutathione and malondialdehyde (Ko et al. 1996).
G. Pharmacokinetics
After oral administration of schisandrin at a dose of 15 mg to healthy male subjects, the
average value of the maximum plasma concentration of schisandrin was 96.1 ng/ml.
The plasma concentration of this substance could be monitored for 8 h after adminis-
tration (Ono et al. 1995).
After intravenous administration of gomisin at doses of 1.6, 4.0 and 10 mg/kg
of body weight, the serum concentration of the drug decreased biphasically, and the
terminal elimination half-life at each dose was about 70 minutes (Matsuzaki et al. 1991).
Dose-dependency was observed for the area under the concentration-time curve (AUC).
The serum concentration gomisin A increased rapidly, and reached a maximum within
15 to 30 min when administered orally. The Cmax and the AUC values were not
exactly dose-dependent, but the values increased with a dose-up of gomisin A. Matsuzaki
et al. showed that the biotransformation of gomisin A to Met. B was very rapid when
administered both intravenously and orally. The AUC value of Met. B after oral admin-
istration of gomisin A at a dose of 1.6 mg/kg was relatively larger than at any other
dosages. The authors suggested that gomisin A extensively underwent the first pass
effect in rats. In addition, it was found that more than 80 per cent of gomisin A was
bound with rat serum protein in vitro and in vivo (Matsuzaki et al. 1991).
H. Toxicity
The toxicity of Fructus Schisandrae and its lignans were reported to be low. No death
was observed in mice given 5 g/kg herb intragastrically. Luan and He (1992) reported
that the LD50 of the herb in mice was 7.4 g/kg (intraperitoneal injection). However,
some components of Fructus Schisandrae are very toxic to insects, and can be used as
insecticides. Miyazawa et al. (1998) isolated two insecticidal lignans, gomisin B and
gomisin N, from the n-hexane extract of Fructus Schisandrae, and showed that the LC50
values of gomisin B and gomisin N were 0.031 and 0.125 mmol/ml, respectively.
RADIX OPHIOPOGONIS
Radix Ophiopogonis (Maidong) is the root tuber of Ophiopogon japonicus (Thunb.)

Ker-Gawl. The root is sweet with a slightly bitter taste. In traditional Chinese medi-
cine, it is used for nourishing the stomach, promoting the production of body fluid, and
nourishing the lung. It is also used for nourishing the heart and the treatment of angina
pectoris.
I. Chemical constituents of Radix Ophiopogonis

Maidong was found to have a complex chemical profile, which can be classified into the
following types.
Component herbs 99
Figure 5.5 Chemical structures of volatile oils found in Radix Ophiopogonis.
A. Volatile oils (Figure 5.5)

The volatile oil was found to contain camphor, linalool, terpinen-4-ol, β-patchoulene,
longifolene, cyperene, α-humulene, guaiol, α-patchoulene, and jasmololone (Zhu 1991).
B. Saponins (Figure 5.6)

Maidong is rich in saponins such as ophiopogonin A, B, C and D (Yang 1987b) where
the aglycone is ruscogenin, and ophiopogonin B′, C′ (Tada 1972) and D′ (Tada 1972;
Yang 1987a) where the aglycones are diosgenin, diosgenin-3-O-[α-L-rhamnopyranosiyl
(1→2)] [(3-O-acetyl)-β-D-xylopyransoyl (1→3)]-β-D-glucopyranoside (Yang 1987a)
and diosgenin-3-O-[(2-O-acetyl)-α-L-rhamnopyransoyl (1→2)] [β-D-xylopyranosyl
(1→3)]-β-D-glucopyranoside (Tada 1972).
C. Flavanoids
Maidong contains homoisoflavanoids such as methylophiopoganone A and B, ophio-
pogonanone A, 5,7-dihydroxy-6-aldehydo-8-methyl-3-(3,4-methylenedioxylbenzyl)-4-
chromanone, 5,6-dihydroxy-6-aldehydo-8-methyl-3-(4-methoxybenzyl)-4-chromanone,
5-hydroxy-6-aldehydo-7-methoxy-8-methyl-3-(3,4-methylenedioxybenzyl)-
4-chromanone (Kaneda 1983), 5-hydroxy-6-aldehydo-7-methoxy-8-methyl-3-(4-
methoxybenzyl)-4-chromanone (Kaneda 1983; Zhu 1989), 5,7-dihydroxy-6-methyl-3-
(4-methoxybenzyl)-4-chromanone (Kaneda 1983), 6-aldehydo-isoophiopogone B,
6-aldehydo-isoophiopogone A (Zhu 1987), and 5,7-dihydroxy-6,8-dimethyl-3-(3,4-
methylenedioxybenzyl)-4-chromone (Liu 1991).
100 Siu-Po Ip et al.
Figure 5.6 Chemical structures of saponins found in Radix Ophiopogonis.
Figure 5.7 Chemical structures of flavanoids found in Radix Ophiopogonis.

Component herbs 101
D. Others
Besides saponins and flavanoids, Maidong also contains β-sitosterol, stigmasterol, β-
sitosterol-β-D-glucoside (Zhu 1989), borneol glucoside (Kaneda 1983), borneol-
glucoside-(6,1)-apioside (Kaneda 1983; Zhu 1989), and vitamin A.
II. Pharmacology of Radix Ophiopogonis

A. Cardiovascular effects
It has been reported that Ophiopogon japonicus increased coronary blood flow, produced a
strophanthin-like inhibitory action on Na+/K+ ATPase and increased myocardial con-
tractility (Huang 1998b). Clinical trials on 101 cases of coronary disease and angina
pectoris found that treating the patients with Ophiopogon japonicus showed an improve-
ment in symptoms and ECG pattern (Huang 1998b).
In vitro study on cultured human and mouse myocardial cell lines (Dong et al. 1995)
demonstrated that Ophiopogon japonicus significantly enhanced growth metabolism and
prolonged the survival time of these cells. The herb also increased the occurrence of
spontaneous contraction of mouse myocardial cells (Dong et al. 1995).
Chen et al. (1990) showed that Ophiopogon total saponins extracted from the root of
Ophiopogon japonicus prevented and antagonized arrhythmias induced by chloroform,
epinephrine, BaCl2 and aconitine in dogs. The saponins effectively reduced the incidence
of ventricular arrhythmia produced by ligation of the left anterior descending coronary
artery, but without producing any changes in the hemodynamic indices. By means of
contact electrode and intracellular microelectrode techniques, the saponins were found
to shorten action potential duration (APD) at 10, 50 and 90 per cent of repolarization.
The saponins also decreased action potential amplitude (APA) and maximum velocity
of depolarization (Vmax). In addition, the authors demonstrated that Ophiopogon total
saponins increased the effective refractory period (ERP)/APD ratio, and prevented or
abolished the arrhythmokinesis provoked by ouabain and aconitine. Therefore, Chen
et al. (1990) suggested that the anti-arrhythmic properties of the saponins were mediated
by the blocking of sodium and calcium channels.
B. Anti-hypoxic effect
It has been reported that treating mice with ophiopogonin C at a dose of 20 mg/kg
prolonged the survival time of the animals under hypoxic condition. A recent study
showed that an injection of alcoholic extract of Radix Ophiopogon japonicus at doses
of 12.5 and 25 g/kg increased anoxia tolerance in mice by 15.4 and 31.7 per cent,
respectively (Li and Zhang 2000).
C. Immunomodulatory effects
Yu et al. (1991) showed that treating mice with polysaccharides isolated from Radix
Ophiopogon japonicus increased the weight of the spleen in animals. After an intravenous
injection of charcoal particles, the rate of clearance was enhanced in mice pretreated
with the polysaccharides. Ophiopogon japonicus also promoted the production of serum
specific antibody hemolysin, antagonized leukopenia caused by cyclophosphamide and
enhanced the hemagglutination rate in rabbits (Yu et al. 1991).
D. Hypoglycemic effect
The hypoglycemic action of polysaccharides isolated from Radix Ophiopogonis was
studied in normal and alloxan-diabetic mice. In normal mice, these polysaccharides
(100 mg/kg, p.o.) significantly lowered blood sugar by 54 per cent at 11 h after admin-
istration. In alloxan-diabetic mice, the polysaccharides (200 mg/kg, p.o.) demonstrated
marked hypoglycemic actions from 4 h and up to 24 h after the administration (Zhang
and Wang 1993).
E. Antitussive effects
Ophiopogonin, a steroid saponin from Radix Ophiopogonis, showed strong antitussive
effects on bronchitic animals (Miyata et al. 1991).
A decrease in neutral endopeptidase activity could increase coughing-inducing
substances such as substance P, which stimulates C-fiber endings and induces cough-
ing. Treating animals with ophiopogonin has been shown to prevent the decrease in
neutral endopeptidase activity (Miyata et al. 1992). Inhalation of substance P, capsaicin,
or neurokinin A could induce coughing in normal and bronchitic guinea pigs. The
coughing was strongly suppressed by oral administration of 0.5 or 1.0 mg ophiopogonin
(Miyata et al. 1992). Treating guinea pig with ophiopogonin also suppressed coughing
induced by endogenous tachykinin after the administration of phosphoramidon, an
inhibitor of enkephalinase and neutral endopeptidase (Miyata et al. 1992).
F. Toxicity
Intravenous administration of 1 ml of Radix Ophiopogon japonicus extract to mice (cor-
responding to 2 g of the herbs and 100–12500 times the dosage of man) produced no
mortality or toxic reactions. The LD50 value of intraperitoneal injection of Ophiopogon
japonicus in mice was 20.6 g/kg (Zhu 1998a).
Using the micronucleus test of mouse bone marrow cell, Liu and Wu (1999)
showed that Radix Ophiopogonis at doses of 1.7 and 3.4 g/kg decreased micronuclei
frequencies induced by cyclophosphamide. Treating the animals with Radix Ophiopogonis
at a dose of 6.8 g/kg significantly inhibited the micronuclei frequencies. Thus, the
author suggested that Radix Ophiopogonis had no genetic toxicity, and may be used as
an antimutagen at a high dose (Liu and Wu 1999).
REFERENCES
Ahumada, H., Hermosilla, J., Hola, R., Pena, R., Wittwer, F., and Wegmann, E. (1989)
Studies on the effect of Schizandra chinensis extract on horses submitted to exercise and
maximum effort. Phytotherapy Research, 3, 175–179.
Atopkina, L.N., Malinovskaya, G.V., Elyakov, G.B., Uvarova, N.I., Woerdenbag, H.J., Koulman,
A., Pras, N., and Potier, P. (1999) Cytotoxicity of natural ginseng glycosides and semisynthetic
analogues. Planta Medica, 65, 30–34.
Bahrke, M.S. and Morgan, W.P. (1994) Evaluation of the ergogenic properties of ginseng.
Sports Medicine, 18, 229–248.
Benishin, C.G. (1992) Actions of ginsenoside Rb1 on choline uptake in central cholinergic
nerve endings. Neurochemistry International, 21, 1–5.
Component herbs 103
Besso, H., Kaisai, R., Saruwatari, Y., Fuwa, T., and Tanaka, O. (1982a) Ginsenoside-Ra1 and
ginsenoside-Ra2, new dammarane-saponins of Ginseng root. Chemical and Pharmaceutical
Bulletin, 30, 2380–2385.
Besso, H., Kasai, R., Wei, J., Wang, J.F., Saruwatari, Y., Fuwa T., and Tanaka O. (1982b)
Further studies on dammarane-saponins of American Ginseng, root of Panax quinquefolium
L. Chemical and Pharmaceutical Bulletin, 30, 4534–4538.
Bhattacharya, S.K. and Mitra, S.K. (1991) Anxiolytic activity of Panax ginseng roots: an
experimental study. Journal of Ethnopharmacology, 34, 87–92.
Brekhman, I.I. and Dardymov, I.V. (1969) Pharmacological investigation of glycosides from
Ginseng and Eleutherococcus. Lloydia, 32, 46–51.
Chen, M., Yang, Z.G., Zhu, J.T., Xiao, Z.Y., and Xiao, R. (1990) Anti-arrhythmic effects and
electrophysiological properties of Ophiopogon total saponins. Acta Pharmacologica Sinica, 11,
161–165.
Chen, X. and Lee, T.J. (1995) Ginsenosides-induced nitric oxide-mediated relaxation of the
rabbit corpus cavernosum. British Journal of Pharmacology, 115, 15–18.
Chen, Y.Y., Shu, Z.B., and Li, L.N. (1976) Studies on Fructus schisandrae. IV. Isolation and
determination of the active compounds (in lowering high SGPT levels) of Schisandra chinensis
Baill. Scientia Sinica, 19, 276–290.
Choi, Y.D., Rha, K.H., and Choi, H.K. (1999) In vitro and in vivo experimental effect of
Korean red ginseng on erection. Journal of Urology, 162, 1508–1511.
Cui, J.F., Garle, M., Bjorkhem, I., and Eneroth, P. (1996) Determination of aglycones of
ginsenosides in ginseng preparations sold in Sweden and in urine samples from Swedish
athletes consuming ginseng. Scandinavian Journal of Clinical and Laboratory Investigation, 56,
151–160.
Dabrowski, Z., Wrobel, J.T., and Wojtasiewicz, K. (1980) Structure of an acetylenic com-
pound from Panax ginseng. Phytochemistry, 19, 2464–2465.
D’Angelo, L., Grimaldi, R., Caravaggi, M., Marcoli, M., Perucca, E., Lecchini, S., Frigo, G.M.,
and Crema, A. (1986) A double-blind, placebo-controlled clinical study on the effect of a
standardized ginseng extract on psychomotor performance in healthy volunteers. Journal of
Ethnopharmacology, 16, 15–22.
Dong, J.D., Xia, H.Y.T., Yu, X.P., Zhao, W.M., and Zhou, Y.P. (1995) The effects of herbs
and chromium on virus infection and growth metabolism in myocardial cells. Virologica Sinica,
10, 104–110.
Fulder, S.J. (1981) Ginseng and the hypothalamic-pituitary control of stress. American Journal
of Chinese Medicine, 9, 112–118.
Gao, R.L., Xu, C.L., and Jin, J.M. (261) Effect of total saponins of Panax ginseng on hemato-
poietic progenitor cells in normal human and aplastic anemia patients. Chinese Journal of
Integrated Traditional and Western Medicine, 12, 285–287.
Gillis, C.N. (1997) Panax ginseng pharmacology: a nitric oxide link?. Biochemical Pharmacology,
54, 1–8.
Hancke, J., Rurgos, R., and Wikman, G. (1994) Schizandra chinensis, a potential phytodrug
for recovery of sport horses. Fitoterapia, 65, 113–118.
Hiai, S., Yokoyama, H., Oura, H., and Kawashima, Y. (1983) Evaluation of corticosterone
secretion-inducing activities of ginsenosides and their prosapogenins and sapogenins. Chemical
and Pharmaceutical Bulletin, 31, 168–174.
Hikino H., Kiso Y., Taguchi H., and Ikeya Y. (1984) Validity of the oriental medicines. LX.
Liver protective drugs. 11. Antihepatotoxic actions of lignoids from Schisandra chinensis
fruits. Planta Medica, 50, 213–218.
Hikino, H., Oshima, Y., Suzuki, Y., and Konno, C. (1985) Isolation and hypoglycemic activity
of panaxans F, G and H, glycans of Panax ginseng roots. Shoyakugaku Zasshi, 39, 331–333.
Huang, K.C. (1998a) Ginseng. In K.C. Huang (ed.), The pharmacology of Chinese herbs, CRC
Press, Florida, p. 17– 44.
Huang, K.C. (1998b) Mar Dong. In K.C. Huang (ed.), The pharmacology of Chinese herbs, CRC
Press, Florida, p. 107–108.
Iida, Y., Tanaka, O., and Shibata, S. (1968) Studies on saponins of Ginseng: the structure of
ginsenoside-Rg1. Tetrahedron Letters, 5449–5453.
Ikeya, Y., Taguchi H., and Itaka Y. (1976) The constituents of Schisandra chinensis Baill. The
structure of a new lignan, gomisin D. Tetrahedron Letters, 1359–1362.
Ikeya, Y., Taguchi, H., and Yosioka, I. (1978a) The constituents of Schisandra chinensis Baill.
The structures of three new lignans, angeloylgomisin H, tigloylgomisin H and benzoylgomisin
H and the absolute structure of schisandrin. Chemical and Pharmaceutical Bulletin, 26, 328–
332.
Ikeya, Y., Taguchi, H., and Yosioka, I. (1978b) The constituents of Schisandra chinensis Baill.
The structures of two new lignans, pre-gomisin and gomisin J. Chemical and Pharmaceutical
Bulletin, 26, 682–684.
Ikeya, Y., Taguchi, H., Yosioka, I., and Kobayashi, H. (1978c) The constituents of Schisandra
chinensis Baill. The structure of two new lignans, gomisin N and tigloylgomisin P. Chemical
Ikeya, Y., Taguchi H., Yosioka, I., and Kobayashi, H. (1979a) The constituents of Schisandra
chinensis Baill. I. Isolation and structure determination of five new lignans, gomisin A, B, C,
F and G, and the absolute structure of schisandrin. Chemical and Pharmaceutical Bulletin,
27, 1383–1394.
Ikeya, Y., Taguchi, H., Yosioka, I., Iitaka, Y., and Kobayashi, H. (1979b) The constituents of
Schisandra chinensis Baill. II. The structure of a new lignan, gomisin D. Chemical and Phar-
maceutical Bulletin, 27, 1395–1401.
Ikeya, Y., Taguchi, H., Yosioka, I., and Kobaysashi, H. (1979c) The constituents of Schisandra
chinensis Baill. V. The structures of four new lignans, gomisin N, gomisin O, epigomisin
O and gomisin E and transformation of gomisin N to deangeloylgomisin B. Chemical and
Pharmaceutical Bulletin, 27, 2695–2709.
Ikeya, Y., Taguchi, H., Yosioka, I., and Kobayashi, H. (1979d) The constituents of
Schisandra chinensis Baill. III. The structures of four new lignans, gomisin H and its derivat-
ives, angeloyl-, tigloyl- and benzoyl-gomisin H. Chemical and Pharmaceutical Bulletin, 27,
1576–1582.
Ikeya, Y., Taguchi, H., Yosioka, I., and Kobayashi, H. (1979e) The constituents of Schisandra
chinensis Baill. IV. The structures of two new lignans, pre-gomisin and gomisin J. Chemical
Ikeya, Y., Taguchi, H., and Yosioka, I. (1979f) The constituents of Schisandra chinensis Baill.
The cleavage of the methylenedioxy moiety with lead tetraacetate in benzene and the structure
of angeloylgomisin Q. Chemical and Pharmaceutical Bulletin, 27, 2536–2538.
Ikeya, Y., Taguchi, H., and Yosioka, I. (1980a) The constituents of Schisandra chinensis Baill. VII.
The structures of three new lignans, (–)-gomisin K1 and (+)-gomisin K2 and K3. Chemical
Ikeya, Y., Taguchi, H., Yosioka, I., and Kobayashi, H. (1980b) The constituents of Schisandra
chinensis Baill. VIII. The structures of two new lignans, tigloylgomisin P and angeloylgomisin
P. Chemical and Pharmaceutical Bulletin, 28, 3357–3361.
Ikeya, Y., Taguchi, H., and Yosioka, I. (1982a) The constituents of Schisandra chinensis Baill. X.
The structure of γ-schizandrin and four new lignans, (-)-gomisins L1 and L2, (±)-gomisin M1
and (+)-gomisin M2. Chemical and Pharmaceutical Bulletin, 30, 132–139.
Ikeya, Y., Taguchi, H., and Yosioka, I. (1982b) The constituents of Schisandra chinensis Baill.
XII. Isolation and structure of a new lignan, gomisin R, the absolute structure of wuweizisu
C and isolation of schisantherin D. Chemical and Pharmaceutical Bulletin, 30, 3207–3211.
Ikeya, Y., Ookawa, N., Taguchi, H., and Yosioka, I. (1982c) The constituents of Schisandra
chinensis Baill. XI. The structures of three new lignans, angeloylgomisin O and angeloyl- and
benzoyl-isogomisin O. Chemical and Pharmaceutical Bulletin, 30, 3202–3206.
Component herbs 105
Ikeya, Y., Taguchi, H., Mitsuhashi, H., and Takeda, S. (1988a) The constituents of Schizandra
chinensis Baill. XIV. A lignan from Schizandra chinensis. Phytochemistry, 27, 569–573.
Ikeya, Y., Kanatani, H., Hakozaki, M., Taguchi, H., and Mitsuhashi, H. (1988b) The con-
stituents of Schizandra chinensis Baill. XV. Isolation and structure determination of two new
lignans gomisin S and gomisin T. Chemical and Pharmaceutical Bulletin, 36, 3974–3979.
Inoue, M., Wu, C.Z., Dou, D.Q., Chen, Y.J., and Ogihara, Y. (1999) Lipoprotein lipase activation
by red ginseng saponins in hyperlipidemia model animals. Phytomedicine, 6, 257–265.
Ip, S.P., Poon, M.K., Wu, S.S., Che, C.T., Ng, K.H., Kong, Y.C., and Ko, K.M. (1995) Effect
of schisandrin B on hepatic glutathione antioxidant system in mice: protection against
carbon tetrachloride toxicity. Planta Medica, 61, 398–401.
Ip, S.P. and Ko, K.M. (1996) The crucial antioxidant action of schisandrin B in protecting
against carbon tetrachloride hepatotoxicity in mice: a comparative study with butylated
hydroxytoluene. Biochemical Pharmacology, 52, 1687–1693.
Ip, S.P., Poon, M.K., Che, C.T., Ng, K.H., Kong, Y.C., and Ko, K.M. (1996) Schisandrin B
protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione
redox status in mouse liver. Free Radical Biology and Medicine, 21, 709–712.
Ip, S.P., Ma, C.Y., Che, C.T., and Ko, K.M. (1997) Methylenedioxy group as determinant
of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-
intoxicated mice. Biochemical Pharmacology, 54, 317–319.
Jin, S.H., Park, J.K., Nam, K.Y., Park, S.N., and Jung, N.P. (1999) Korean red ginseng saponins
with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-
induced learning disability and spatial working memory in mice. Journal of Ethnopharmacology,
66, 123–129.
Kaneda, N., Nakanishi, H., Kuraishi, T., and Katori, T. (1983) Studies on the Components of
Ophiopogon Roots (China). I. Journal of the Pharmaceutical Society of Japan, 103, 1133–1139.
Kasai, R., Besso, M., Tanaka, O., Saruwatari, Y., and Fuwa, T. (1983) Saponins of red Ginseng.
Chemical and Pharmaceutical Bulletin, 31, 2120–2125.
Kenarova, B., Neychev, H., Hadjiivanova, C., and Petkov, V.D. (1990) Immunomodulating activ-
ity of ginsenoside Rg1 from Panax ginseng. Japanese Journal of Pharmacology, 54, 447– 454.
Keum, Y.S., Park, K.K., Lee, J.M., Chun, K.S., Park, J.H., Lee, S.K., Kwon, H., and Surh, Y.J.
(2000) Antioxidant and anti-tumor promoting activities of the methanol extract of heat-
processed ginseng. Cancer Letters, 150, 41– 48.
Kim, H.S., Oh, K.W., Rheu, H.M., and Kim, S.H. (1992) Antagonism of U-50,488H-
induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms.
Pharmacology, Biochemistry and Behavior, 42, 587–593.
Kim, H.S., Kang, J.G., Seong, Y.H., Nam, K.Y., and Oh, K.W. (1995) Blockade by ginseng
total saponin of the development of cocaine induced reverse tolerance and dopamine receptor
supersensitivity in mice. Pharmacology, Biochemistry and Behavior, 50, 23–27.
Kim, H.S. and Kim, K.S. (1999) Inhibitory effects of ginseng total saponin on nicotine-
induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity. Behavioural
Brain Research, 103, 55–61.
Kim, J.Y., Germolec, D.R., and Luster, M.I. (1990) Panax ginseng as a potential immuno-
modulator: studies in mice. Immunopharmacology and Immunotoxicology, 12, 257–276.
Kimura, T., Saunders, P.A., Kim, H.S., Rheu, H.M., Oh, K.W., and Ho, I.K. (1994) Inter-
actions of ginsenosides with ligand-bindings of GABA(A) and GABA(B) receptors. General
Pharmacology, 25, 193–199.
Kimura, Y., Okuda, H., and Arichi, S. (1988) Effects of various ginseng saponins on
5-hydroxytryptamine release and aggregation in human platelets. Journal of Pharmacy and
Pharmacology, 40, 838– 843.
Kitagawa, I., Yoshikawa, M., Yashihara, M., Hayashi, T., and Taniyama, T. (1983a) Chemical
studies on crude drug procession. I. On the constituents of Ginseng Radix Rubra. Yakugaku
Zasshi, 103, 612–622.
Kitagawa, I., Taniyama, T., Hayashi, T., and Yoshikawa, M. (1983b) Malonyl-ginsenosided-
Rb1, -Rb2, -Rc and Rd, four new malonylated dammarane-type triterpene oligosaccharides
from Ginseng radix. Chemical and Pharmaceutical Bulletin, 31, 3353–3356.
Ko, K.M., Ip, S.P., Poon, M.K., Wu, S.S., Che, C.T., Ng, K.H., and Kong, Y.C. (1995a)
Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats:
protection against carbon tetrachloride toxicity. Planta Medica, 61, 134–137.
Ko, K.M., Mak, D.H.F., Li, P.C., Poon, M.K., and Ip, S.P. (1995b) Enhancement of hepatic
glutathione regeneration capacity by a lignan-enriched extract of fructus schisandrae in rats.
Japanese Journal of Pharmacology, 69, 439– 442.
Ko, K.M., Mak, D.H.F., Li, P.C., Poon, M.K.T., and Ip, S.P. (1996) Protective effect of a
lignan-enriched extract of Fructus schisandrae on physical exercise induced muscle damage
in rats. Phytotherapy Research, 10, 450– 452.
Kochetkov, N.K., Khorlin, A.Y., Chizhov, O.S., and Sheichenko, V.I. (1961) Schizandrin, a
lignan of unusual structure. Tetrahedron Letters, 730–734.
Koizumi, H., Sanada, S., Ida, Y., and Shoji, J. (1982) Studies on the saponins of Ginseng. IV.
On the structure and enzymatic hydrolysis of ginsenoside Ra1. Chemical and Pharmaceutical
Bulletin, 30, 2393–2398.
Konno C., Sugiyama K., Kano M., Takahashi M., and Hikino H. (1984) Validity of the oriental
medicines. LXX. Antidiabetes drugs. 1. Isolation and hypoglycemic activity of panaxans A,
B, C, D and E, glycans of Panax ginseng roots. Planta Medica, 50, 434–436.
Konno, C., Murakami, M., Oshima, Y., and Hikino, H. (1985) Validity of the Oriental
medicines. CVI. Antidiabetes drugs. 19. Isolation and hypoglycemic activity of panaxans Q,
R, S, T and U, glycans of Panax ginseng roots. Journal of Ethnopharmacology, 14, 69–74.
Kubo, S., Ohkura, Y., Mizoguchi, Y., Matsui-Yuasa, I., Otani, S., Morisawa, S., Kinoshita, H.,
Takeda, S., Aburada, M., and Hosoya, E. (1992) Effect of Gomisin A (TJN-101) on liver
regeneration. Planta Medica, 58, 489– 492.
Lee, D.C., Lee, M.O., Kim, C.Y., and Clifford, D.H. (1981) Effect of ether, ethanol and aqueous
extracts of ginseng on cardiovascular function in dogs. Canadian Journal of Comparative
Medicine, 45, 182–187.
Lee, S.C., Moon, Y.S., and You, K.H. (2000) Effects of red ginseng saponins and nootropic
drugs on impaired acquisition of ethanol-treated rats in passive avoidance performance.
Journal of Ethnopharmacology, 69, 1–8.
Lee, S.J., Sung, J.H., Lee, S.J., Moon, C.K., and Lee, B.H. (1999) Antitumor activity of a novel
ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin.
Cancer Letters, 144, 39– 43.
Li, L.Q. and Zhang, L.J. (2000) Pharmacological action of Ophiopogon japonicus. Journal of
Hebei Traditional Chinese Medicine and Pharmacology, 15, 34–35.
Li, R.Q. and Zhang, Y.S. (1985) Analysis of the chemical constituents of ginseng polysaccharide.
Chi Trad Herb Drugs, 16, 389–391.
Li, X.G. and Teng, F.T. (1979) Studies on the triterpenoid in Panax ginseng. Acta Botanica
Sinica, 21, 181–185.
Li, X.J., Zhao, B.L., Liu, G.T., and Xin, W.J. (1990) Scavenging effects on active oxygen
radicals by schizandrins with different structures and configurations. Free Radical Biology and
Medicine, 9, 99–104.
Lim, J.H., Wen, T.C., Matsuda, S., Tanaka, J., Maeda, N., Peng, H., Aburaya, J., Ishihara, K.,
and Sakanaka, M. (1997) Protection of ischemic hippocampal neurons by ginsenoside Rb1,
a main ingredient of ginseng root. Neuroscience Research, 28, 191–200.
Lin, T., Liu, G., and Pan, Y. (1992) Protective effect of schisanhenol against oxygen radical
induced mitochondrial toxicity on rat heart and liver. Biomedical and Environmental Sciences, 5,
57–64.
Lin, T.J., Liu, G.T., Li, X.J., Zhao, B.L., and Xin, W.J. (1990) Detection of free radical
scavenging activity of schisanhenol by electron spin resonance. Acta Pharmacologica Sinica,
11, 534–539.
Component herbs 107
Lin, T.J., Liu, G.T., Pan, Y., Liu, Y., and Xu, G.Z. (1991) Protection by schisanhenol against
adriamycin toxicity in rat heart mitochondria. Biochemical Pharmacology, 42, 1805–1810.
Liu, B. and Wu, G.H. (1999) Genetic toxicity of Radix Ophiopogonis. Journal of Norman
Bethune University of Medica Sciences, 25, 129–130.
Liu, C.J., Zeng, Q., Liu, D., Zhang, J., and Yang, Y.D. (1991) Studies on the Constituents
of Homoisoflavonoids of Ophiopogon japonicus of Hang. Chinese Traditional and Herbal Drugs,
22, 60.
Liu, C.X. and Xiao, P.G. (1992) Recent advances on ginseng research in China. Journal of
Ethnopharmacology, 36, 27–38.
Liu, G.T., Bao, T.T., Wei, H.L., and Song, Z.Y. (1980) Induction of hepatocyte microsomal
cytochrome P-450 by Schizandrin B in mice. Acta Pharmaceutica Sinica, 15, 206–211.
Liu, G.T. and Wei, H.L. (1985) Induction of hepatic microsomal monooxygenases by schisandrol
in rats. Acta pharmacologica Sinica, 6, 41– 44.
Liu, K., Abe, T., Sekine, S., Goto, Y., Iijima, K., Kondon, K., Matsukawa, M., Tian, J., Wu, W.,
Zhang, B., Chen, L., Zhang, H., Zhang, X., Zhao, H., and Song, X. (1998) Experimental study
on the scavenging effects of ginsenosides on oxygen free radicals using model of heterotopic
heart transplantation in rats. Annals of Thoracic and Cardiovascular Surgery, 4, 188–191.
Liu, K.T., Cresteil, T., Le Provost, E., and Lesca, P. (1981) Specific evidence that schizandrins
induce a phenobarbital-like cytochrome P-450 form separated from rat liver. Biochemical and
Biophysical Research Communications, 103, 1131–1137.
Liu, K.T. and Lesca, P. (1982) Pharmacological properties of dibenzo[a,c]cyclooctene derivat-
ives isolated from Fructus Schizandrae chinensis. I. Interaction with rat liver cytochrome P-
450 and inhibition of xenobiotic metabolism and mutagenicity. Chemico-Biological Interactions,
39, 301–314.
Liu, W.K., Xu, S.X. and Che, C.T. (2000) Anti-proliferative effect of ginseng saponins on
human prostate cancer cell line. Life Sciences, 67, 1297–1306.
Lu, H. and Liu, G.T. (1991) Effect of dibenzo[a,c]cyclooctene lignans isolated from Fructus
schizandrae on lipid peroxidation and anti-oxidative enzyme activity. Chemico-Biological
Interactions, 78, 77–84.
Lu, H. and Liu, G.T. (1992) Anti-oxidant activity of dibenzocyclooctene lignans isolated from
Schisandraceae. Planta Medica, 58, 311–313.
Lu, Y.J., Zeng, X.Y., Ning, L.D., Wang, H.A., and Wang, H.Y. (1985) Studies on the
Chemical Constituents of Ginseng. V. Isolation and Identification of Steroid-saponins and
Triterpene-saponins of Ginseng. Journal of Shenyang College of Pharmacy, 2, 177–184.
Luan, L. and He, M. (1992) Estimation of apparent pharmacokinetic parameters of herbal
Houttuyniae and dructus Schizandrae with the method of acute mortality of animals. Journal
of China Medical University, 21, 183–186.
Luo, S.D., Liu, A.Y., and Liu, Y.Y. (1983) Comparison of active constituents and pharmaco-
logical effects of ginseng root and ginseng rhizome. Chemical and Pharmaceutical Bulletin, 18,
468–470.
Luo, Y.M., Cheng, X.J., and Yuan, W.X. (1993) Effects of ginseng root saponins and ginsenoside
Rb1 on immunity in cold water swim stress mice and rats. Acta Pharmacologica Sinica, 14,
401– 404.
Maffei Facino, R., Carini, M., Aldini, G., Berti, F., and Rossoni, G. (1999) Panax ginseng admin-
istration in the rat prevents myocardial ischemia-reperfusion damage induced by hyperbaric
oxygen: evidence for an antioxidant intervention. Planta Medica, 65, 614–619.
Matsuura, H., Kasai, R., Tanaka, O., Saruwatari, Y., Kunihiro, K., and Fuwa, T. (1984)
Further studies on dammarane-saponins of Ginseng root. Chemical and Pharmaceutical Bulletin,
32, 1188–1192.
Matsuda, H., Namba, K., Fukuda, S., Tani, T., and Kubo, M. (1986a) Pharmacological study
on Panax ginseng C. A. Meyer. III. Effects of red ginseng on experimental disseminated
intravascular coagulation. (2). Effects of ginsenosides on blood coagulative and fibrinolytic
systems. Chemical and Pharmaceutical Bulletin, 34, 1153–1157.
Matsuda, H., Namba, K., Fukuda, S., Tani, T., and Kubo, M. (1986b) Pharmacological study
on Panax ginseng C.A. Meyer. IV. Effects of red ginseng on experimental disseminated
intravascular coagulation. (3). Effect of ginsenoside-Ro on the blood coagulative and fibrinolytic
system. Chemical and Pharmaceutical Bulletin, 34, 2100–2104.
Matsuzaki, Y., Matsuzaki, T., Takeda, S., Koguchi, S., Ikeya, Y., Mitsuhashi, H., Sasaki, H.,
Aburada, M., Hosoya, E., and Oyama, T. (1991) Studies on the metabolic fate of gomisin A
(TJN-101). I. Absorption in rats. Journal of the Pharmaceutical Society of Japan, 111, 524–530.
Mei, B., Wang, Y.F., Wu, J.X., and Chen, W.Z. (1994) Protective effects of ginsenosides on
oxygen free radical induced damages of cultured vascular endothelial cells in vitro. Acta
Pharmaceutica Sinica, 29, 801–808.
Miyata, T., Fuchikamki, J., Kai, H., and Takahama, K. (1991) Characteristics of antitussive action
of Mai-Men-Dong-Tang and Ophiopogonin, a steroid saponin extracted from Mai-Men-
Dong. Kanpo to Men’eki Arerugi, 5, 60–73.
Miyata, T., Fuchikamki, J., Kai, H., and Takahama, K. (1992) Effects of Bakumondo-to
and an extracted ingredient of Bakumondo on tachykinin-induced coughing and neutral
endopeptidase activity. Kanpo to Men’eki Arerugi, 6, 29–37.
Miyazawa, M., Hirota, K., Fukuyama, M., Ishikawa, Y., and Kameoka, H. (1998) Insecticidal
lignans against Drosophila melanogaster from fruits of Schisandra chinensis. Natural Products
Letters, 12, 175–180.
Mizoguchi, Y., Kawada, N., Ichikawa, Y., and Tsutsui, H. (1991a) Effect of gomisin A in the
prevention of acute hepatic failure induction. Planta Medica, 57, 320–324.
Mizoguchi, Y., Shin, T., Kobayashi, K., and Morisawa, S. (1991b) Effect of gomisin A in an
immunologically-induced acute hepatic failure model. Planta Medica, 57, 11–14.
Mochizuki, M., Yoo, Y.C., Matsuzawa, K., Sato, K., Saiki, I., Tono-oka, S., Samukawa, K., and
Azuma, I. (1995) Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-
Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biological and Pharmaceutical Bulletin,
18, 1197–1202.
Moon, J., Yu, S.J., Kim, H.S., and Sohn, J. (2000) Induction of G(1) cell cycle arrest and
p27(KIP1) increase by panaxydol isolated from Panax ginseng. Biochemical Pharmacology, 59,
1109–1116.
Nagai, H., Yakuo, I., Aoki, M., Teshima, K., Ono, Y., Sengoku, T., Shimazawa, T., Aburada, M.,
and Koda, A. (1989) The effect of gomisin A on immunologic liver injury in mice. Planta
Medica, 55, 13–17.
Nagai, Y., Tanaka, O., and Shibata, S. (1971) Chemical studies on the oriental plant drugs. XXIV.
Structure of ginsenoside-Rg1, a neutral saponin of Ginseng root. Chemical and Pharmaceutical
Bulletin, 27, 881–892.
Niu, X.Y., Wang, W.J., Bian, Z.J., and Ren, Z.H. (1983) Effects of schizandrol on the central
nervous system. Acta Pharmaceutica Sinica, 18, 416– 421.
Odani, T., Tanizawa, H., and Takino, Y. (1983) Studies on the absorption, distribution,
excretion and metabolism of ginseng saponins. II. The absorption, distribution and excretion
of ginsenoside Rg1 in the rat. Chemical and Pharmaceutical Bulletin, 31, 292–298.
Odashima, S., Ohta, T., Kohno, H., Matsuda, T., Kitagawa, I., Abe, H., and Arichi, S. (1985)
Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides. Cancer
Research, 45, 2781–2784.
Ohta, Y. and Hirose, Y. (1968a) Structure of Sesquicarene. Tetrahedron Letters, 1251–1254.
Ohta, Y. and Hirose, Y. (1968b) New Sesquiterpenoids from Schisandra chinensis. Tetrahedron
Letters, 2483–2485.
Ohtaki, Y., Nomura, M., Hida, T., Miyamoto, K., Kanitani, M., Aizawa, T., and Aburada, M.
(1994) Inhibition by gomisin A, a lignan compound, of hepatocarcinogenesis by 3′-methyl-
4-dimethylaminoazobenzene in rats. Biological and Pharmaceutical Bulletin, 17, 808–814.
Ono, H., Matsuzaki, Y., Wakui, Y., Takeda, S., Ikeya, Y., Amagaya, S., and Maruno, M. (1995)
Determination of schizandrin in human plasma by gas chromatography-mass spectrometry.
Journal of Chromatography B: Biomedical Applications, 674, 293–297.
Component herbs 109
Onomura, M., Tsukada, H., Fukuda, K., Hosokawa, M., Nakamura, H., Kodama, M., Ohya,
M., and Seino, Y. (1999) Effects of ginseng radix on sugar absorption in the small intestine.
American Journal of Chinese Medicine, 27, 347–354.
Oshima, Y., Konno, C., and Hikino, H. (1985) Isolation and hypoglycemic activity of panaxans
I, J, K and L, glycans of Panax ginseng roots. Journal of Ethnopharmacology, 14, 255–259.
Pieralisi, G., Ripari, P., and Vecchiet, L. (1991) Effects of a standardized ginseng extract
combined with dimethylaminoethanol bitartrate, vitamins, minerals, and trace elements on
physical performance during exercise. Clinical Therapeutics, 13, 373–382.
Poplawski, J., Wrobel, J.T., and Glinka, T. (1980) Panaxydol, a new polyacetylenic epoxide
from Panax ginseng roots. Phytochemistry, 19, 1539–1541.
Sanada, S., Kondo, N., Shoji, J., Tanaka, O., and Shibata, S. (1974b) Studies on the saponins of
Ginseng. II. Structures of ginsenoside-Re, -Rf, and -Rg2. Chemical and Pharmaceutical Bulle-
tin, 22, 2407–2412.
Sanada, S. and Shoji, J. (1978) Studies on the saponins of Ginseng. III. Structures of ginsenoside-
Rb3 and 20-glucoginsenoside-Rf. Chemical and Pharmaceutical Bulletin, 26, 1694–1697.
Sanda, S., Kondo, N., Shoji, J., Tanaka, O., and Shibata, S. (1974a) Studies on the saponins of
Ginseng. I. Structures of ginsenoside-Ro, -Rb1, -Rb2, -Rc and -Rd. Chemical and Pharmaceutical
Bulletin, 22, 421– 428.
Shibata, S., Tanaka, O., Shoji, J., and Saiti, H. (1985) Chemistry and pharmacology of Panax.
In H. Wagner, H. Hikino, and N.R. Farnsworth (eds), Economic and Medicinal Plant Research,
Academic Press, London, p. 217–284.
Shim, S.C., Koh, H.Y., and Han, B.H. (1983) Polyacetylenes from Panax ginseng roots.
Phytochemistry, 22, 1817–1818.
Shoji, J. (1985) Recent advances in the chemical studies on ginseng. In H.M. Chang, H.W.
Yeung, W.W. Tso, A. Koo, (eds), Advances in Chinese Medicinal Material Research, World
Science, Singapore, p. 455– 469.
Song, W. and Tong, Y. (1983) Occurrence and assay of some important lignans in Wu Wei Zi
(Schisandra chinensis) and its allied species. Acta Pharmaceutica Sinica, 18, 138–143.
Song, W.Z., Tong, Y.Y., and Cheng, L.S. (1990) Lignans of the genus Schisandra in China.
Journal of Natural Product Research and Development, 2, 51–58.
Sotaniemi, E.A., Haapakoski, E., and Rautio, A. (1995) Ginseng therapy in non-insulin-
dependent diabetic patients. Diabetes Care, 18, 1373–1375.
Tada, A. and Shoji, J. (1972) Studies on the Constituents of Ophiopogonis Tube. II. On the
Structure of Ophiopogonin B. Chemical & Pharmaceutical Bulletin, 20, 1729–1734.
Taguchi, H. and Ikeya, Y. (1975) The constituents of Schisandra chinensis Baill. I. The structures
of gomisim A, B and C. Chemical and Pharmaceutical Bulletin, 23, 3296–3298.
Taguchi, H. and Ikeya, Y. (1977) The constituents of Schisandra chinensis Baill. The structures
of two new lignans, gomisin F and G, and the absolute structures of gomisin A, B and C.
Chemical and Pharmaceutical Bulletin, 25, 364–366.
Takahashi, M. and Yoshikura, M. (1966a) Studies on the components of Panax ginseng
C.A. Meyer. IV. On the structure of a new acetylene derivative ‘panaxynol’ (2). Synthesis of
1,7,9-heptadecatrien-4-yn-3-ol. Yakugaku Zasshi, 86, 1051–1053.
Takahashi, M. and Yoshikura, M. (1966b) Studies on the components of Panax ginseng
C.A. Meyer. V. On the structure of a new acetylene derivative, ‘panaxynol’ (3). Synthesis of
1,9-(cis)-heptadecadiene-4,6-diyn-3-ol. Yakugaku Zasshi, 86, 1053–1056.
Takeda, S., Kase, Y., Arai, I., Hasegawa, M., Sekiguchi, Y., Funo, S., Aburada, M., Hosoya, E.,
Mizoguchi, Y., and Morisawa, S. (1986) Effects of TJN-101 ((+)-(6s,7s,R-biar)-5,6,7,8-
tetrahydro-1,2,3,12-tetramethoxy-6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]
cyclooctenol) on liver regeneration after partial hepatectomy, and on regional hepatic blood
flow and fine structure of the liver in normal rats. Folia Pharmacologica Japonica, 88, 321–330.
Takeda, S., Arai, I., Hasegawa, M., Tatsugi, A., Aburada, M., and Hosoya, E. (1988) Effect of
gomisin A (TJN-101), a lignan compound isolated from Schisandra fruits, on liver function
in rats. Folia Pharmacologica Japonica, 91, 237–244.
Tam W. (1992) Panax ginseng C.A.Mey. In W. Tam, G. Eisenbrand (eds), Chinese Drugs of
Plant Origin : Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Springer-
Verlag, Hong Kong, p. 711–737.
Tan, R., Li, L.N., and Fang, Q.C. (1986) The stereostructure of wuweizisu B. Planta Medica,
52, 49–51.
Teng, C.M., Kuo, S.C., Ko, F.N., Lee, J.C., Lee, L.G., Chen, S.C., and Huang, T.F. (1989)
Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochimica et
Biophysica Acta, 990, 315–320.
Tsang, D., Yeung, H.W., Tso, W.W., and Peck, H. (1985) Ginseng saponins: influence on
neurotransmitter uptake in rat brain synaptosomes. Planta Medica, 221–224.
Voces, J., Alvarez, A.I., Vila, L., Ferrando, A., Cabral,d. O., and Prieto, J.G. (1999) Effects of
administration of the standardized Panax ginseng extract G115 on hepatic antioxidant func-
tion after exhaustive exercise. Comparative Biochemistry and Physiology, Part C Pharmacology,
Toxicology, Endocrinology. 123, 175–184.
Wakabayashi, C., Hasegawa, H., Murata, J., and Saiki, I. (1997) In vivo antimetastatic action
of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after
oral administration. Oncology Research, 9, 411– 417.
Wakabayashi, C., Murakami, K., Hasegawa, H., Murata, J., and Saiki, I. (1998) An intestinal
bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis
in tumor cells. Biochemical and Biophysical Research Communications, 246, 725–730.
Wang, B.X., Yang, M., Jin, Y.L., Cui, Z.Y., and Wang, Y. (1990) Studies on the hypoglycemic
effect of ginseng polypeptide. Acta Pharmaceutica Sinica, 25, 401– 405.
Wen, T.C., Yoshimura, H., Matsuda, S., Lim, J.H., and Sakanaka, M. (1996) Ginseng root
prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia.
Acta Neuropathologica, 91, 15–22.
Xiaoguang, C., Hongyan, L., Xiaohong, L., Zhaodi, F., Yan, L., Lihua, T., and Rui, H. (1998)
Cancer chemopreventive and therapeutic activities of red ginseng. Journal of Ethnopharmacology,
60, 71–78.
Xu, S.X., Wang, Q.H., Zhang, G.G., Lu, Y.J., Chen, G.X., and Chen, Y.J. (1988) Studies
on the Chemical Constituents of Panax ginseng C.A. Meyer XII. Study on the Liposoluble
Constituents of Panax ginseng C.A. Meyer. Journal of Shenyang College of Pharmacy, 5, 16–19.
Yahara, S., Sakamoto, C., Nohara, T., Niiho, Y., Nakajima, Y., and Ito, H. (1993) Thymoquinol
Glucosides from Schisandrae Fructus. Japanese Journal of Pharmacognosy, 47, 420– 422.
Yamada, S., Murawaki, Y., and Kawasaki, H. (1993) Preventive effect of gomisin A, a lignan
component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Biochemical
Pharmacology, 46, 1081–1085.
Yamaguchi, Y., Haruta, K., and Kobayashi, H. (1995) Effects of ginsenosides on impaired
performance induced in the rat by scopolamine in a radial-arm maze. Psychoneuroendocrinology,
20, 645–653.
Yamamoto, M., Masaka, M., Yamada, K., Hayashi, Y., Hirai, A., and Kumagai, A. (1978)
Stimulatory effect of ginsenosides on DNA, protein and lipid synthesis in rat bone marrow
and participation of cyclic nucleotides. Arzneimittel-Forschung, 28, 2238–2241.
Yang, M., Wang, B.X., Jin, Y.L., Wang, Y., and Cui, Z.Y. (1990) Effects of ginseng poly-
saccharides on reducing blood glucose and liver glycogen. Acta Pharmacologica Sinica, 11,
520–524.
Yang, Y., Wu, T., He, K., and Fu, Z.G. (1999) Effect of aerobic exercise and ginsenosides
on lipid metabolism in diet-induced hyperlipidemia mice. Acta Pharmacologica Sinica, 20,
563–565.
Yang, Z., Xiao, R., and Xiao, Z.Y. (1987a) Study on Chemical Constituents of Ophiopogon
japonicus (Thumb) of Sichuan (I). West China Journal of Pharmaceutical Science, 2, 57–60.
Yang, Z., Xiao, R., and Xiao, Z.Y. (1987b) Study on Chemical Constituents of Ophiopogon
japonicus (Thumb) of Sichuan (II). West China Journal of Pharmaceutical Science, 2, 121–124.
Component herbs 111
Yasukawa, K., Ikeya, Y., Mitsuhashi, H., Iwasaki, M., Aburada, M., Nakagawa, S., Takeuchi, M.,
and Takido, M. (1992) Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-
13-acetate in two-stage carcinogenesis in mouse skin. Oncology, 49, 68–71.
Yim, T.K. and Ko, K.M. (1999) Schisandrin B protects against myocardial ischemia-reperfusion
injury by enhancing myocardial glutathione antioxidant status. Molecular and Cellular Bio-
chemistry, 196, 151–156.
Yu, B.Y., Yin X., Zhang, C.H., and Xu, G.J. (1991) Immunity study on polysaccharide from
tuberous roots of Ophiopogon japonicus (L. f.) Ker-Gawl. Journal of Chinese Pharmaceutical
University, 22, 286–288.
Yun, T.K. (1996) Experimental and epidemiological evidence of the cancer-preventive effects
of Panax ginseng C.A. Meyer. Nutrition Reviews, 54, S71–S81.
Yun, T.K. (1999) Update from Asia. Asian studies on cancer chemoprevention. Annals of the
New York Academy of Sciences, 889, 157–192.
Yun, Y.S., Moon, H.S., Oh, Y.R., Jo, S.K., Kim, Y.J., and Yun, T.K. (1987) Effect of red
ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and
benzo(a)pyrene. Cancer Detection and Prevention, Supplement. 1, 301–309.
Zhang, G. and Ding, W. (1962) A preliminary report on the phytophthora root rot of Panax
ginseng C.A. Meyer. China Journal of Chinese Materia Medica, 15, 18–19.
Zhang, H.X., Sun, Y.X., Wang, S.Q., Jiang, W.P., and Yang, L.R. (1985) Analysis of the volatile
constituents of Jilin ginseng. Chinese Science Bulletin, 30, 195–199.
Zhang, L.L., Xiao, Y.L., and Li, X.G. (1989) Isolation and Identification of the Salicymide of
Red Ginseng. Zhong Yao Cai, 12, 33–34.
Zhang, T.M., Wang, B.E., and Liu, G.T. (1989) Action of schizandrin B, an antioxidant, on
lipid peroxidation in primary cultured hepatocytes. Acta Pharmacologica Sinica, 10, 353–356.
Zhang, T.M., Wang, B.E., and Liu, G.T. (1992) Effect of schisandrin B on lipoperoxidative
damage to plasma membrane of rat liver in vitro. Acta Pharmacologica Sinica, 13, 255–258.
Zhang, W.X. and Wang, N.H. (1993) Hypoglycemic action of the polysaccharides from Radix
Ophiopogonis in alloxan-induced diabetic mice. Chinese Traditional and Herbal Drugs, 24,
30–31.
Zhu, Y.P. (1998a) Mai Dong. In Y.P. Zhu (ed.), Chinese Materia Medica: Chemistry, Pharmacology
and Applications, Harwood Academic Publishers, Amsterdam, p. 629–632.
Zhu, Y.P. (1998b) Wu Wei Zi. In Y.P. Zhu (ed.), Chinese Materia Medica: Chemistry, Pharmacology
and Applications, Harwood Academic Publishers, Amsterdam, p. 653–657.
Zhu, Y.X., Yan, D.K., and Tu, G.S. (1987) Isolation and Identification of Homoisoflavanones
from Maidong (Ophiopogon japonicus (Thumb) Ker-Gawl). Acta Pharmaceutica Sinica, 22, 679–
684.
Zhu, Y.X., Liu, L.Z., Lin, D.K., and Wang, W. (1989) Studies on Chemical Constituents of
Ophiopogon japonicus. China Journals of Chinese Materia Medica, 14, 359–360.
Zhu, Y.X., Liu, L.Z., Wang, W., Ling, D.K., and Sun, Z.P. (1991) Studies on Chemical Con-
stituents of Essential Oil of Ophiopogon japonicus. Chinese Journal of Pharmaceutical Analysis, 11,
21–23.
Ziemba, A.W., Chmura, J., Kaciuba-Uscilko, H., Nazar, K., Wisnik, P., and Gawronski, W.
(1999) Ginseng treatment improves psychomotor performance at rest and during graded
exercise in young athletes. International Journal of Sport Nutrition, 9, 371–377.
112 Liang-Yuan Zheng
6 Contemporary applications
of a traditional formula:
manufacture of Shengmai San
(SMS) preparations and
their applications
Liang-Yuan Zheng
[Translated by Kam-Ming Ko]
Shengmai San (SMS), also known as Shengmai Yin, is a traditional Chinese medicinal
formula that is usually administered as a decoction. Over the past decades, a number
of modern dosage forms have evolved from the modification of the original formula
including the Codonopsis- and Ginseng-formula (Chen 1998; Hu et al. 1998). Although
the official dosage form of SMS described in the Year 2000 edition of the Chinese
Pharmacopoeia (CP) is an oral tonic, official standards of other dosage forms, such as
capsule, syrup, granule, tea bag, tablet, and injection have also been established by the
Ministry of Health, China.
RECENTLY STANDARDIZED FORMULATIONS

AND DOSAGE
I. Year 2000 edition of the Chinese Pharmacopoeia
A. Shengmai tonic
Formulation (Ministry of Health, China 2000): Radix Ginseng 100 g, Radix Ophiopogonis
200 g, and Fructus Schisandrae 100 g for every 1000 ml of extract. Taken thrice daily,
10 ml each time, equivalent to a daily consumption of Radix Ginseng 3 g, Radix
Ophiopogonis 6 g, and Fructus Schisandrae 3 g.
RECOGNIZED STANDARD PREPARATIONS OF SMS BY

THE MINISTRY OF HEALTH, CHINA
I. Shengmai capsules
Formulation (Ministry of Health, China 1993): Radix Ginseng 330 g, Radix Ophiopogonis
660 g, and Fructus Schisandrae 330 g for every 1000 capsules. Taken thrice daily,
3 capsules each time, equivalent to a daily consumption of Radix Ginseng 2.97 g,
Radix Ophiopogonis 5.94 g, and Fructus Schisandrae 2.97 g.
Contemporary applications 113
II. Shengmai tonic
Formulation (Ministry of Health, China 1995): Radix Codonopsis 300 g, Radix Ophiopogonis
200 g, and Fructus Schisandrae 100 g for every 1000 ml of extract. Taken thrice daily,
10 ml each time, equivalent to a daily consumption of Radix Codonopsis 9 g, Radix
Ophiopogonis 6 g, and Fructus Schisandrae 3 g.
III. Shengmai syrup (Codonopsis-formula)

Formulation (Ministry of Health, China 1996a): same as Shengmai Tonic.
IV. Shengmai granules (Codonopsis-formula)

Formulation (Ministry of Health, China 1996b): Radix Codonopsis 300 g, Radix Ophiopogonis
200 g, Fructus Schisandrae 100 g, and excipients for granulation. Taken thrice daily,
10 g each time.
V. Shengmai tea-bag
Formulation (Ministry of Health, China 1996c): Radix Ginseng 100 g, Radix Ophiopogonis
200 g, and Fructus Schisandrae 100 g for every 1000 tea-bags. Taken thrice daily,
0.4 g (1 tea-bag) each time by soaking in hot water. The dosage is equivalent to
a daily consumption of Radix Ginseng 0.3 g, Radix Ophiopogonis 0.6 g, and Fructus
Schisandrae 0.3 g.
VI. Shengmai tablets (Codonopsis-formula)

Formulation (Ministry of Health, China 1997a): Radix Codonopsis 300 g, Radix
Ophiopogonis 200 g, and Fructus Schisandrae 100 g for every 1000 tablets. Taken thrice
daily, 8 tablets each time, equivalent to a daily consumption of Radix Codonopsis 7.2 g,
Radix Ophiopogonis 4.8 g, and Fructus Schisandrae 2.4 g.
VII. Shengmai injection

Formulation (Ministry of Health, China 1997b): Radix Ginseng Destillata 100 g, Radix
Ophiopogonis 312 g, and Fructus Schisandrae 156 g for every 1000 ml; standard prepara-
tions of 2 ml, 10 ml and 20 ml are available. Administered 1–2 times a day, by
intramuscular injection at a dose of 2–4 ml each time, equivalent to a daily consump-
tion of Radix Ginseng Destillata 0.4–0.8 g, Radix Ophiopogonis 1.25–2.5 g, and Fructus
Schisandrae 0.62–1.25 g. Intravenous infusion: 20–60 ml each time, equivalent to a
daily consumption of Radix Ginseng Destillata 2–6 g, Radix Ophiopogonis 6.2–18.7 g,
and Fructus Schisandrae 3.12–9.36 g.
CONTEMPORARY DOSAGE FORMS AND
PROCESSING TECHNIQUES
I. Shengmai tonic (oral liquid)
A. Preparation
The three component herbs, Radix Ginseng, Radix Ophiopogonis, and Fructus Schisandrae are
ground into powder and processed as described in the Chinese Pharmacopoeia (under
the Percolation section in Appendix 10: Extract and Liquid Extraction). Using 65 per
cent ethanol as the solvent, the herb powder is soaked for 24 hours before percolation. A
total of 4500 ml of percolate is collected and concentrated to 250 ml at reduced pressure.
After cooling, the concentrate is diluted with 400 ml of water, filtered, and mixed with
300 ml of 60 per cent syrup and a suitable amount of preservative. The pH value of
the mixture is then adjusted to a suitable range and made up to 1000 ml, allowed to
settle, filtered, bottled, and then sterilized (Ministry of Health, China 2000).
B. Process improvement studies:

(a) The degree of translucence of the mixture could be enhanced by de-fatting with
paraffin after the adjustment of pH. (b) The degree of translucence of the mixture
could also be enhanced by adjusting the pH value to 8, the intermediate was allowed to
settle before diluting to oral liquid. (c) The effect of fine processing using the natural
flocculant, chitosan, has been found to be superior to ultracentrifugation and as good
as alcohol precipitation (Zhang 1994; Chang et al. 1998; Shao 1999).
II. Shengmai capsules
A. Preparation
Two hundred grams of the Ginseng is ground into fine powder and left aside for use
in later processes. The rest of the Ginseng (130 g) is ground into coarse powder, soaked
in 75 per cent ethanol for 24 hours, and extracted by percolation as described in the
Appendix (p.17) in the Chinese Pharmacopoeia. Fructus Schisandrae is ground into coarse
powder and extracted by distillation. The residue, together with Radix Ophiopogonis,
is extracted twice with boiling water, filtered, and combined. The combined extract is
then concentrated, made up with ethanol to contain 60 per cent (v/v) of ethanol in
composition, allowed to settle and filtered. The filtrate is then concentrated (with
the ethanol recycled) and combined with the Ginseng percolate, Schisandrae distillate
(volatile oil) and the Ginseng fine powder. The mixture is then granulated, dried, and
filled into 1000 capsules (Ministry of Health, China 1993).
III. Shengmai tonic (Codonopsis-formula)
A. Preparation
The 3 component herbs, Radix Codonopsis, Radix Ophiopogonis, and Fructus Schisandrae,
are extracted twice with boiling water: 2 hours for the first extraction and 1.5 hours for
the second. The extracts are combined, filtered, and concentrated to a volume of about
300 ml and cooled. Ethanol (600 ml) is then added, allowed to stand for 24 hours
and filtered. The filtrate is then concentrated at reduced pressure to form a paste,
after which a trace amount of water is added to facilitate filtration. Mono-sugar syrup
(300 ml) and preservative are added to this second filtrate, and made up to 1000 ml
with water. The mixture is allowed to settle and then filtered. The product is ready
after bottling and sterilization (Ministry of Health, China 1995).
B. Studies on ultrafiltration technique

In the fine processing of Shengmai tonic, ultrafiltration using external pressure and
hollow fiber offers the benefits of short production cycle and high cost efficiency.
Accelerated studies with ultrafiltration technique showed that it could raise the com-
position of the active ingredients, without compromising translucence and hence the
degree of precipitation (Liu et al. 1996).
IV. Shengmai syrup (Codonopsis-formula)
A. Preparation
The three component herbs, Radix Codonopsis, Radix Ophiopogonis and Fructus Schisandrae,
are extracted twice with boiling water; 2 hours for the first extraction and 0.5 hours for
the second. The extracts are combined, filtered and concentrated to a suitable volume,
after which ethanol is added to make up a final ethanol composition of 60 per cent and
allowed to settle for 24 hours. The mixture is then filtered, and the filtrate is concen-
trated at reduced pressure. Cane sugar (650 g) is added to the concentrate with stirring
until it is dissolved. The syrup is then boiled for 30 minutes, after which preservative
is added and made up to 1000 ml with water (Ministry of Health, China 1996a).
V. Shengmai granules (Codonopsis-formula)
A. Preparation
The three component herbs, Radix Codonopsis, Radix Ophiopogonis and Fructus Schisandrae,
are extracted twice with boiling water: 2 hours for the first extraction and 1.5 hours for
the second. The extracts are combined, filtered, and concentrated to a volume of about
300 ml and cooled. Ethanol (600 ml) is then added, allowed to stand for 24 hours and
filtered. The filtrate is then concentrated at reduced pressure until it reaches a relative
density of 1.30(60–65°C) and appears as a clear paste. The paste is mixed with five
parts of cane sugar, granulated and dried (Ministry of Health, China 1996b).
VI. Shengmai tea-bag
A. Preparation
The three component herbs, Radix Codonopsis, Radix Ophiopogonis and Fructus Schisandrae
are ground into coarse powder, mixed, and granulated. The granules could then be
filled into 1000 tea-bags after drying (Ministry of Health, China 1996c).
VII. Shengmai tablets (Codonopsis-formula)
A. Preparation
A portion of the Radix Codonopsis is ground into powder, and the fine powder (about
240 g) is reserved for future use. The volatile oil of Fructus Schisandrae is extracted by
distillation. The aqueous distillant is collected in a separate container, while the residue
together with the coarse powder of Radix Codonopsis and Radix Ophiopogonis, are extracted
twice with water and then filtered. The extract is combined with the aqueous distillant
of Fructus Schisandrae, concentrated to paste form, and mixed with the fine powder of
Radix Codonopsis and excipients. After granulation, the granules are dried and sprayed
with the volatile oil of Fructus Schisandrae. The process is completed by pressing the
granules into 1000 tablets and coating with sugar (Ministry of Health, China 1997a).
VIII. Shengmai injection
A. Preparation
Radix Ginseng Destillata is ground into fine granules, and then extracted 4–5 times with
ethanol (each for 2 hours). The end-point of extraction could be monitored by thin-
layer chromatography (TLC). The extracts are combined, chilled, filtered, and concen-
trated to paste form, and mixed with 400 ml injection grade water. The mixture is then
chilled, filtered, and reserved for future use. Fructus Schisandrae is distilled with steam
until 150 ml of distillate is collected, which is refrigerated for later use. The residue is
extracted three times with water, 40 minutes each time, and the extracts are combined,
filtered, and concentrated to paste form. The paste is then subjected to ethanol precipita-
tion twice, at final ethanol concentrations of 80 and 85 per cent respectively. The ethanol
solutions are then filtered, with the filtrate being combined and ethanol being recycled
in subsequent concentration process. The filtrate is then concentrated to form a paste. The
paste is then mixed with 200 ml injection grade water, chilled, and filtered, after which
the filtrate is boiled for 30 minutes with activated charcoal. The solution is cooled for
a while, and then filtered for later use. A clear aqueous extract of Radix Ophiopogonis
(about 200 ml) is prepared in the same way of Fructus Schisandrae. In preparing the final
dosage form, the aqueous extracts of Radix Ginseng Destillata, Fructus Schisandrae, and
Radix Ophiopogonis and the distillate of Fructus Schisandrae are mixed, filtered and made
up to 1000 ml with injection grade water. The pH of the solution is then adjusted to
7.5, filtered, bottled, sterilized, and ready for use (Ministry of Health, China 1997b).
QUALITY CONTROL AND STANDARDIZATION
I. Shengmai tonic (oral liquid)
A. Physical attributes
A clear liquid that is brownish yellow to pale red in color; mild turbidity on pro-
longed standing; fragrant in scent; sour, sweet, and lightly bitter in taste (Ministry of
Health, China 2000).
B. Authentication
(a) An aliquot of the sample (20 ml) is partitioned with 20 ml n-butanol. The butanol
fraction is evaporated to dryness, and the residue is refluxed with 15 ml sulfuric acid-
acidified ethanol (45 per cent)(7:100 v/v) for 1 hour. The ethanol is evaporated, and
the aqueous solution is partitioned with 10 ml of chloroform. The chloroform fraction
is taken and dehydrated with anhydrous sodium sulfate. After filtration, the solvent is
concentrated to a final volume of 1 ml, serving as the test sample. A mixed-standard
solution containing 1 mg/ml each of panaxadiol and panaxatriol is prepared by dis-
solving the standards in anhydrous ethanol. Qualitative analysis is performed using
the thin-layer chromatographic (TLC) method as described in Appendix VI B of the
Chinese Pharmacopoeia. Aliquots (10 µl) of the test sample and standard solution are
applied to a silica-G plate, and eluted with cyclohexane-propanol (2:1). After drying,
the TLC plate is sprayed with sulfuric acid-methanol (1:1) solution, heated at 105°C
for 10 minutes, and observed under UV light (365 nm). The test sample should have
fluorescent spots appearing at the equivalent positions as compared with standards.
(b) An aliquot of the sample (10 ml) is mixed with 0.5 ml hydrochloric acid and
1 ml water. The mixture is boiled for 5 minutes, allowed to cool down, and then
partitioned with 20 ml of chloroform. The chloroform fraction is concentrated to a
final volume of 1 ml, serving as the test sample. A standard herb of Radix Ophiopogonis
(1 g) is heated with 20 ml of water for 10 minutes. The extract could then serve as the
standard solution after filtration and addition of 0.5 ml hydrochloric acid. Analysis is
performed using TLC method as described in Appendix VI B of the Chinese Phar-
macopoeia. Aliquots (5 µl) of the test sample and standard solution are applied to a
silica-G plate, and eluted with chloroform-propanol (4:1). After drying, the TLC plate
is sprayed with 10 per cent sulfuric acid-ethanol solution, and heated at 100°C until the
color spots become clear and vivid. The test sample should have color spots appearing
at the equivalent positions as compared with standards.
C. Physicochemical analyses
Relative density not less than 1.08 (Appendix VII A, CP). pH value should fall
between 4.5 and 7.0 (Appendix VII G, CP). Others should meet the relevant require-
ments for mixture in the Chinese Pharmacopoeia (Appendix I,J).
II. Shengmai capsules
The product exists in capsule form, with brownish-yellow powdery content; fragrant
in scent; sour, sweet, and lightly bitter in taste (Ministry of Health, China 1993).
B. Authentication
The content of 10 capsules is dissolved in 20 ml of water, put into a separating funnel,
and partitioned with n-butanol (20 ml). The butanol fraction is then filtered and
evaporated to dryness. The residue is then reconstituted with 15 ml of a 7 per cent
sulfuric acid-45 per cent ethanol (7.4:93) solution, and refluxed for 1 hour, after which
the ethanol component is evaporated, and the remaining solvent is partitioned with
10 ml of chloroform. The chloroform fraction is taken out, dehydrated with anhydrous
sodium sulfate, filtered, and concentrated to 1 ml, serving as the test sample. A mixed-
standard solution containing 1 mg/ml each of panaxadiol and panaxatriol is prepared
by dissolving the standards in anhydrous ethanol. Qualitative analysis is performed
using TLC method as described in Appendix VI B of the Chinese Pharmacopoeia.
Aliquots (10 µl) of the test sample and standard solution are applied to a silica-G
plate, and eluted with cyclohexane-propanol (2:1). After drying, the TLC plate is
sprayed with sulfuric acid-methanol (1:1) solution, heated at 105°C for 10 minutes,
and observed under UV light (365 nm). The test sample should have fluorescent spots
appearing at the equivalent positions as the standards.
Moisture content is determined by Method 1 as described in p.30 of the Appendix
(C.P.) and should not exceed 7.5 per cent. Others should meet the relevant require-
ments for capsules in the Chinese Pharmacopoeia (Appendix p.16).
III. Shengmai tonic (Codonopsis-formula)
The product exists as a brownish-yellow liquid; fragrant in scent; sweet and sour in
taste (Ministry of Health, China 1995).
B. Physicochemical analyses
Relative density not less than 1.08 (C.P. Appendix p.34). Others should meet the
relevant requirements for mixture in the Chinese Pharmacopoeia (Appendix p.15).
IV. Shengmai syrup (Codonopsis-formula)
The product exists as a brownish paste; fragrant in scent; sweet in taste (Ministry of
Health, China 1996a).
Relative density not less than 1.24 (C.P. Appendix VII A). Others should meet the
relevant requirements for syrup in the Chinese Pharmacopoeia (Appendix I H).
V. Shengmai granules (Codonopsis-formula)
The product exists as brownish-yellow granules; fragrant in scent; sweet in taste
(Ministry of Health, China 1996b).
It should meet the relevant requirements for granules in the Chinese Pharmacopoeia
(Appendix I C).
VI. Shengmai tea-bag
The product exists as brownish-yellow granules; fragrant in scent; astringent and
slightly bitter in taste (Ministry of Health, China 1996c).
B. Authentication
(a) Microscopic examination reveals resin canals that contain yellowish secretory droplets
or granules; round cluster crystals of calcium oxalate with a diameter of 20–68 µm and
sharp edges; needle-like crystals of calcium oxalate, 24–50 µm in length and 3 µm
in diameter, exist in a clustered or dispersed pattern. Pale brownish-yellow sclereid
(stone cells) in the seed-coat and epidermis, characterized by their polygonal appearance,
thick walls, fine pores, and pale brownish substances in the cellular space.
(b) Sample of the product (4 g) is soaked in boiling water (50 ml) for 10 minutes,
with gentle heating to maintain mild boiling. The soaking solution is then decanted,
cooled, and partitioned with 50 ml n-butanol. The butanol fraction is then evaporated to
dryness. The residue is reconstituted with 15 ml of a sulfuric acid-45 per cent ethanol
(7:10) solution, and refluxed for 1 hour, after which the ethanol component is evaporated
(about 7 ml solvent will remain) and made up to 10 ml with water. The solution is
partitioned with 20 ml chloroform, which is then taken out, dehydrated with anhydrous
sodium sulfate, filtered, and concentrated to 1 ml, serving as the test sample. A mixed-
standard solution containing 1 mg/ml each of panaxadiol and panaxatriol is prepared
by dissolving the standards in anhydrous ethanol. Qualitative analysis is performed
using the TLC method as described in Appendix VI B of the Chinese Pharmacopoeia.
Aliquots (6 µl) of the test sample and standard solution are applied to a silica-G plate
and eluted with cyclohexane-propanol (2:1). After drying, the TLC plate is sprayed
with a 10 per cent sulfuric acid-methanol solution, heated at 105°C for 10 minutes,
cooled, and observed under UV light (365 nm). The test sample should have fluorescent
spots appearing at the equivalent positions as compared with standards.
The water soluble content of the product is determined by the heat soaking extraction
method as described in the Chinese Pharmacopoeia (Appendix X A), except that the
solution is kept boiling for 10 minutes. The total soluble content should not be less
than 50.0 per cent. Others should meet the relevant requirements for tea preparations
in the Chinese Pharmacopoeia (Appendix I T).
VII. Shengmai tablets (Codonopsis-formula)
The product exists as a coated tablet with brownish content after the removal of the
coating; sweet and sour in taste.
B. Authentication
(a) Sample of the product (three tablets) is de-coated, ground into powder, and suspended
in 15 ml of 50 per cent ethanol. After filtration, three drops of the filtrate is spotted onto
a filter paper, dried in air, and sprayed with 0.1 per cent bromophenol blue-ethanol solu-
tion. Yellow spots should appear in the blue background. When two drops of 0.2 per
cent bromcresol green-ethanol solution are added to 2 ml of the filtrate, the solution
turns yellow-green following the addition of a drop of 10 per cent sodium hydroxide.
(b) A sample of the product (5 g) is refluxed with 30 ml n-butanol for 2 hours,
filtered, and the filtrate is concentrated to 2 ml, serving as the test sample. Standard
solution of Radix Codonopsis is prepared by refluxing 5 g of the herb with 30 ml
n-butanol as described for the sample. Analysis is performed using the TLC method
as described in Appendix VI B of the Chinese Pharmacopoeia. Aliquots (1 µl) of the
test sample and standard solution are applied to a silica-G plate, and eluted with
n-butanol-ethanol-water (25:3:2). After drying, the TLC plate is stained by spraying
it with a 10 per cent sulfuric acid-ethanol solution and then heating at 105°C for
10 minutes. The test sample should have grayish brown spots appearing at the equival-
ent positions as compared with standards.
Others should meet the relevant requirements for tablets in the Chinese Pharmacopoeia
(Appendix I D).
VIII. Shengmai injection
The product exists as pale yellow or brownish-yellow, clear liquid (Ministry of Health,
China 1997).
B. Authentication
(a) A sample of the product (10 ml) is evaporated to dryness in a water bath, and the
residue is dissolved in 2 ml of ethanol, serving as the test sample. A mixed-standard
solution containing 2 mg/ml each of ginsenosides Rb1, Re and Rg1 are prepared in
ethanol. Qualitative analysis is performed using the TLC method as described in
Appendix VI B of the Chinese Pharmacopoeia. Aliquots (2– 4 µl) of the test sample
and standard solution are applied to a silica-G plate, and eluted with chloroform-
methanol-water (75:20:2). After drying, the TLC plate is stained by spraying it with
a 10 per cent sulfuric acid-ethanol solution and then heating at 105°C for a few
minutes. After cooling, the TLC plate is observed under UV light (365 nm). The test
sample should have fluorescent spots appearing at the equivalent positions as com-
pared with standards.
(b) Sample of the product (40 ml) is mixed with 3 ml hydrochloric acid, and
heated in a water bath for 1 hour. After cooling, the solution is partitioned with 30 ml
diethyl ether. The ethereal layer is dried, and the residue is dissolved in 1ml chloro-
form, serving as the test sample. Authenticated Radix Ophiopogonis (2 g) is extracted
by heating with water for 30 minutes, being filtered and concentrated to about
40 ml. A standard solution is then prepared as described for test samples. Qualitative
analysis is performed using TLC method as described in Appendix VI B of the Chinese
Pharmacopoeia. Aliquots (5–10 µl) of the test sample and standard solution are applied
to a silica-G plate, and eluted with chloroform-propanol (4:1). After drying, the TLC
plate is stained by spraying it with a 10 per cent sulfuric acid-ethanol solution, and
then being heated at 105°C for 5 minutes. The test sample should have colored spots
appearing at the equivalent positions as compared with standards.
(c) Sample of the product (50 ml) is concentrated to 25 ml in a water bath and trans-
ferred to a separating funnel. It is then partitioned three times with chloroform (10 ml
each time), filtered, evaporated to near dryness, and then reconstituted with 1 ml of
chloroform, serving as the test sample. Standard solution of schisahenol (0.5 mg/ml) is
prepared in chloroform. Qualitative analysis is performed using the TLC method as
described in Appendix VI B of the Chinese Pharmacopoeia. Aliquots (5–10 µl) of the
test sample and standard solution are applied to a silica-GF254 plate, and eluted with
petroleum ether (30–60°C)-chloroformate-formic acid (14:5:1). After drying, the TLC
plate is observed under UV light (254 nm). The test sample should have colored spots
appearing at the equivalent positions as compared with standards.
The pH value should be 5.0–7.0. A microbial test should meet the requirements
described by the Chinese Pharmacopoeia (Appendix VIII B). A pyrogen test should be
performed at a dose of 2ml/kg in a rabbit and meet the requirements as described
(C.P. Appendix VIII B).
Hemolytic test (Ham’s Test)
(a) Preparation of 2 per cent RBC suspension: Blood obtained from a rabbit by
cardiac puncture is collected into a glass bead-containing vessel. Fibrinogen is removed
by sonicating the blood sample for a few minutes. The defibrinated blood is mixed with
physiological saline, centrifuged, and the clear supernatant is decanted. The sedimented
red blood cells are washed 3–4 times with physiological saline until the supernatant
does not turn red after centrifugation. A 2 per cent (v/v) RBC suspension is prepared
by reconstituting the red cells in physiological saline and used on the same day.
(b) Test Method: with five sterile test tubes, 0.3 ml of the test sample and 2.2 ml
physiological saline are added to three of them, while saline (2.5 ml) or distilled water
(2.5 ml) is added to the other two, serving as the negative and positive controls respec-
tively. The RBC suspension (2 per cent) (2.5 ml) is then added to each of the five test
tubes, mixed, and incubated at 36.5 ± 0.5°C. There should be no signs of hemolysis
within 3 hours.
Others should meet the relevant requirements for injection preparations in the
Chinese Pharmacopoeia (Appendix I U).
D. Quantitation of ingredients: HPLC method (C.P. Appendix VI D)
Chromatographic conditions and system compatibility: C18-silica column; acetonitrile-
0.05 per cent phosphoric acid (19:81) as the mobile phase; detection wavelength
at 203 nm. The number of theoretic plates for ginsenoside Re should not be less than
4000.
Preparation of standard solutions: Ginsenoside Rg1 (15 mg) and ginsenoside Re
(12 mg), having been demoisturized to stable weight in a P2O5-containing dessicator,
are dissolved and made up to 25 ml with acetonitrile-water (19:81) in a volumetric
flask. The solution is then diluted two-fold with the same solvent in a 10 ml volumetric
flask, making final concentrations of 0.3 mg/ml Rg1 and 0.24 mg/ml Re.
Test sample preparation: Sample of the product (10 ml) is evaporated to near dryness,
and reconstituted in 2 ml of the mobile phase.
Quantitation: 20 µl of the test sample or standard solution is injected into the
HPLC system and quantitated accordingly.
Standards: The product should contain not less than 0.08 mg/ml ginsenoside Rg1 or
0.04 mg/ml ginsenoside Re.
CONTEMPORARY RESEARCH IN QUALITY CONTROL
I. Authentication
(a) The content of 10 capsules is dissolved in 20 ml water, transferred to a separating
funnel, partitioned with 20 ml n-butanol, allowed to settle and then filtered. The butanol
extract is evaporated to dryness, reconstituted, and refluxed with 15 ml of sulfuric
acid-45 per cent ethanol (7.4:93) solution. The ethanol component is evaporated, and
the aqueous solution is partitioned with 10 ml of chloroform. The chloroform fraction
is collected and dehydrated with anhydrous sodium sulfate. After filtration, the solvent
is concentrated to a final volume of 1 ml, serving as the test sample. A mixed-standard
solution containing 1 mg/ml each of panaxadiol and panaxatriol is prepared by dis-
solving the standards in anhydrous ethanol. Qualitative analysis is performed using
the TLC method. Aliquots (10 µl) of the test sample and standard solution are applied
to a silica-G plate, and eluted with cyclohexane-propanol (2:1). After drying, the
TLC plate is stained with sulfuric acid-methanol (1:1) solution, heated at 105°C
for 10 minutes, and observed under UV light (365 nm). The test sample should have
fluorescent spots appearing at the equivalent positions as compared with standards
(Yan et al. 1990; Xie 1990).
(b) Sample of tonic or injection (1 ml) is evaporated to dryness over a water bath,
and reconstituted in 1 ml ethanol, serving as the test sample. Qualitative analysis is
performed using the TLC method. Aliquots (3–5 µl) of the test sample and standard
solution are applied to a silica-G plate, and eluted with chloroform-methanol-water
(80:20:2) for about 15 cm. After drying, the TLC plate is stained by spraying it with
a 10 per cent phosphomolybdenic acid-ethanol solution and heating at 105°C for a
few minutes. The chromatogram should show not less than twelve blue spots (Yan
et al. 1990; Xie 1990).
(c) Using tonic or injection as the test samples and extracts of Fructus Schisandrae,
Radix Ginseng, and Radix Ophiopogonis as standards, qualitative analysis is performed using
the TLC method (Zhe et al. 1988a). Aliquots (10 µl) of the test sample and standard
solution are applied to a silica-G plate, and eluted with chloroform-methanol-water
(80:20:2). The TLC plate is stained with iodine vapor or observed under UV light
(254 nm). The test sample should have fluorescent or colored spots appearing at the
equivalent positions as compared with standards (Yan et al. 1990; Xie 1990).
II. Quantitation of active ingredients

(a) Total saponin content of Ginseng (Zhu et al. 1989): (i) Preparation of test sample
solutions – 10 ml water-saturated n-butanol is added to five separating funnels, numbered
1 through to 5. Shengmai tonic (10 ml) is added to the first funnel, and the counter-
current extraction is performed. Each time the aqueous layer is transferred to the
subsequent funnel, the butanol fraction is extracted with 10 ml fresh distilled water,
yielding a total of five aqueous extracts and five butanol extracts. The aqueous extracts
are combined, and extracted three times with 10 ml water-saturated n-butanol. All
butanol extracts are combined and the solvent was recycled under reduced pressure.
The residue is reconstituted with methanol, transferred to a 5 ml vessel, and made
up to the mark. (ii) TLC Analysis – test samples (20–40 µl) containing about 100 µl
Ginseng saponins are applied to a silica-G TLC plate. After the spots are dried, the
plate is eluted with chloroform-methanol-water (70:55:10) for 15 cm. The elution
tank should have been saturated with glacial acetic acid, placed in a small beaker, for
15 minutes before the analysis. The plate is stained by placing the plate in an iodine
vapor-saturated tank for 1 minute, and the positions of the ginsenosides are marked.
(iii) Colorimetric assay: spots on the silica-G plate are scratched with a stainless steel
knife, and then placed in a screw-capped tube. Experimental blank is set by scratch-
ing equivalent amount of silica gel from blank area of the plate into another tube.
A standard curve is constructed by measuring the absorbance of standard samples.
Test samples are quantitated by comparing the absorbance with the standard curve
or regression analysis according to the formula: Total saponin content (mg/ml) = C
(total saponins in µg)/2 × V (sample volume, µl).
(b) Methylophiopogonone A/B (Zhu et al. 1988b): (i) preparation of sample and
standard solutions – Shengmai tonic (10 ml) is extracted five times, in a counter-current
manner, each with 10 ml ether in five 50 ml-separating funnels. The ethereal layer from
each separating funnel is washed twice with 5 ml of water, and each washing is done
with the same ethereal washing (10 ml). The six ethereal extracts are combined, dried
at reduced pressure, and the residue reconstituted in 2 ml methanol, serving as the
test sample. To prepare the standard solution, 1.65 mg methylophiopogonone A and
2.18 mg methylophiopogonone B in 2 ml methanol, respectively. An aliquot (30 µl)
of this solution is then made up to 1ml with methanol in a volumetric flask and serves
as the mixed-standard solution. (ii) HPLC Analysis – mobile phase: methanol-water-
acetonitrile (64:38:26); column: C18; flow rate: 1.0 mm/min; sensitivity 8; detection
wavelength 297 nm; microprocessing parameters: WIDTH 30, SLOPE 200, DRIFT
0, MINOR 100, T-DBL 0, LOCK 10, STPTM 25, AT-TEN 3, SPEED 2.5, METHOD
41, SPLWT 100, ISWT 1. The sample volumes of the test sample and standard are
10 µl and 5 µl respectively, and the amount is quantitated by comparing the standard
and test values.
(c) Schisandrins (Zhu et al. 1988a): (i) sample extraction – Shengmai tonic (10 ml)
is extracted five times, in a counter-current manner, each with 10 ml ether in five
50 ml-separating funnels. The ethereal layer from each separating funnel is washed twice
with 5 ml water, and each washing is done with the same ethereal washing (10 ml).
The six ethereal extracts are combined, dried at reduced pressure, and stored for future
use. (ii) Preparation of sample and standard solutions – the residue of the above ethereal
extract is reconstituted in 5 ml methanol. An aliquot (1 ml) of the methanol solution
is then added to a 2 ml volumetric flask, combined with 100 µl of an internal standard
solution of naphthalane (3 mg/2 ml methanol) and 50 µl internal standard, made up
to 2 ml with methanol, serving as the standard solution. (iii) HPLC Analysis – mobile
phase 73 per cent methanol; column: C18; flow rate 1.0 ml/min; column pressure
2000 kg/cm; detection wavelength 254 nm; sensitivity 8; microprocessing parameters:
WIDTH 30, SLOPE 200, DRIFT 0, MINOR 100, T-DBL 0, LOCK 4, STPTM 1000,
AT-TEN 3, SPEED 2, METHOD 41, SPLWT 100, ISWT 1 and a recorder speed
of 10 mm/min. The sample volume for both test sample and standard is 3 µl, and the
amount is quantitated by comparing the standard and test values.
III. Manufacturers
There are currently 124 manufactures producing different dosage forms of Shengmai
San (Zhang 1997).
REFERENCES
Chang, J. et al. (1998) Studies on the effect of natural flocculant on the fine processing of
Shengmai San extract, China Journal of Traditional Chinese Medicine, 13(2), 22.
Chen, Q. (1998) Pharmacological and clinical basis of renowned traditional Chinese patent medicines,
People’s Medical Publishing House, China, p.382.
Hu, C.L. et al. (1998) Clinical applications of Shengmai San and its injection, Traditional
Chinese Patent Medicine, 20(12), 34.
Liu, H.Q. et al. (1996) Studies on the application of ultrafiltration techniques in the production
of Shengmai San tonic, Chinese Traditional and Herbal Drugs, 27(4), 209.
Ministry of Health, P.R.China (1993) Traditional Chinese medicine and patent medicine preparations,
7, 47.
Ministry of Health, P.R.China (1995) Traditional Chinese medicine and patent medicine preparations,
10, 41.
Ministry of Health, P.R.China (1996a) Traditional Chinese medicine and patent medicine preparations,
11, 47.
Ministry of Health, P.R.China (1996b) Traditional Chinese medicine and patent medicine preparations,
11, 46.
Ministry of Health, P.R.China (1996c), Traditional Chinese medicine and patent medicine preparations,
11, 45.
Ministry of Health, P.R.China (1997a), Traditional Chinese medicine and patent medicine preparations,
12, 39.
Ministry of Health, P.R.China (1997b), Traditional Chinese medicine and patent medicine preparations,
15, 50.
Ministry of Health, P.R.China (2000), Chinese Pharmacopoeia, 436.
Shao, Y.S. (1999) Methods of removing turbidity in Shengmai San tonic, LiShiZhen Medicine
and Materia Medica, 10(1), 31.
Xie, M. (1990) Zhongyi Fangji Xiandai Yanjiu [Current research in traditional Chinese medicinal
prescriptions], Xue Yuan Press, China, 554.
Yan, K.D. and Jiang, X.R. (1990) Research on the quality control of Shengmai San tonic. In
Y.Q. Yan (ed.) Integrated Study of Shengmai San Tonic, CMPSP, China, pp. 50–97.
Zhang, J.K. (1997) Yiyao Gongzuozhe Yewu Zhishi Shouce [Handbook for Healthcare Workers],
China National Pharmaceutical Industry Corporation, Beijing, 514.
Zhang, M.H. (1994) Comments on the possible improvement in the manufacturing process of
Shengmai San set out in the Chinese Pharmacopoeia, China Journal of Chinese Materia Medica,
19(4), 207.
Zhu, C.X. et al. (1988a) Studies on the chemistry of Shengmai San (SMS) preparations (I) –
determination of active ingredients in Fructus Schisandrae by TLC densitometry, Yaoxue
Fenxi Zazhi, 8(2), 71.
Zhu, C.X. et al. (1988b) Studies on the chemistry of Shengmai San (SMS) preparations (II) –
determination of isoflavanoids in Radix Ophiopogonis by reversed phase HPLC, Yaoxue
Fenxi Zazhi, 8(6), 343.
Zhu, C.X. et al. (1989) Studies on the chemistry of Shengmai San (SMS) preparations (III) –
determination of saponins in Radix Ginseng by TLC, Yaoxue Fenxi Zazhi, 9(1), 5.
126 Glossary
Glossary
Assistant See Monarch, Minister, Assistant and Guide

Asthenia A syndrome produced by the deficiency of vital
energy and essence, lowered resistance and hypofunction
of the body, commonly seen in the individual with
general debility and the patient suffering from a
long-standing illness; manifested as lusterless com-
plexion, listlessness, shortness of breath, weak voice,
palpitation, insomnia, poor appetite, thick and tender
tongue, feeble pulse, etc.
Blood An important component of the body derived from
the refined substance of the food through a series of
complex processes. It circulates in the blood vessels
to nourish all parts of the body.
Blood stasis A morbid condition with stagnation of blood circula-
tion or coagulation of the extravastated blood; mostly
due to stagnation of vital energy, deficiency of vital
energy and blood, blood-heat or trauma.
Channels The main passage connecting different parts of the
body in which the vital energy and blood circulate. See
also Meridian.
Chest bi-syndrome A disorder due to the accumulation of Yin-evils
(phlegm-wetness, blood stasis, etc.) leading to the hypo-
function of the chest-Yang, the stagnation of vital
energy and the obstruction of collaterals; manifested
as feeling of oppression over the chest, chest pain
radiating to the back, shortness of breath, inability
to lie flat, etc.
Cold 1) Referring to the cold-evil, one of the six evils, and
is Yin in nature, usually damages Yang-energy and
affects the activity of vital energy and blood. It may
cause the symptoms such as chillness, fever, headache,
general aching, abdominal pain, diarrhea, etc. 2) Dis-
eases characterized by the hypofunction of the body.
Glossary 127
Cold and heat 1) Two principal syndromes for differential diagnosis
serving as the concrete manifestations of the changes
of Yin and Yang, and considered as a significant refer-
ence for the treatment of disease. 2) Referring to
chilliness and fever.
Collaterals See Meridian
Deficiency See Asthenia
Depletion Also Collapse-syndrome. A syndrome due to exhaus-
tion of vital energy, blood, Yin and Yang and the failure
of important organs, manifested as profuse sweating,
deadly cold limbs, incontinence of urine and feces,
listlessness and fading pulse or even coma.
Treatment by ! Making a diagnosis and selecting the treatment based
Differentiation on the analysis and comprehension of the clinical data
of Signs and collected by the four methods of examination with the
Symptoms basic theories of viscera, meridian and pathogenesis.
Dry; dryness 1) Referring to the dryness-evil, one of the six evils,
and tends to consume the body fluid, and may cause
symptoms as conjunctival congestion, dry mouth and
nose, non-productive cough, hypochondriac pain,
constipation, etc. 2) Referring to dryness-syndrome due
to consumption of Yin-fluid.
Eight Principal The eight aspects for differential diagnosis, i.e., Yin
Syndromes and Yang, superficies and interior, cold and heat, asthenia
and sthenia.
Eight Therapeutic Also: eight medical treatment; including diaphoresis,
Principles inducing emesis, purgation, reconciliation (regulation of the
functional relationship between the internal organs),
warming, heat-clearing, resolution and invigoration.
Guide See Monarch, Minister, Assistant and Guide
Heart One of the five solid viscerae and the most important
one of the body. Its main function is to maintain the
normal blood circulation. In TCM, the heart is con-
sidered to be closely related to the functional activ-
ities of the higher nervous system. The pathological
changes of the heart are reflected in the disturbance
of the blood circulation and the activities of higher
nervous system, especially in that of the mental and
emotional activities. Moreover, the secretion of sweat
glands and the changes of the tongue are also related
to the heart.
Heart-clearing A treatment for clearing away the heat-evil in the
pericardium out of the body by the application of
128 Glossary
drugs with actions of clearing heart-heat, cooling blood
and nourishing Yin-fluid.
Heart-Yang The Yang-energy of the heart. In case of deficiency of
heart-Yang, cold syndrome such as coldness of the limbs,
feeble and impalpable pulse may appear.
Heart-Yin The nutritious fluid of the heart, which is a com-
ponent of blood, bearing a close relation to the
heart-blood physiologically and pathologically, and also
to the condition of lung-Yin and kidney Yin.
Heat 1) Referring to heat-evil. 2) One of the eight principal
syndromes, a syndrome of hyperfunction of Yang-
energy, manifested as heat-syndrome such as fever,
congested conjunctiva, flushed face and thirst, etc.
3) A therapeutic method, i.e., the therapy by warming
or the therapy by expelling cold. 4) One of the four
characters of Chinese medicinal herbs.
Heat-evil The evil that causes symptoms of Yang and heat in
nature, such as fever, noisy breathing, local redness,
swelling, heat and pain, constipation, etc.
Interior U See Superficies and interior
Jue-syndrome 1) A temporary suspension of consciousness. 2) Cold-
ness of the extremities. 3) The critical case of
dysuria.
Liver-Qi Also liver-energy, referring to the function of the liver,
including certain functions of nervous, digestive and
endocrine systems.
Lung One of the five viscerae. Its main functions are
to control respiration, to regulate fluid metabolism
and to help the heart in regulating blood circulation,
so as to provide the substances necessary for the
physiological activities of the organs of the body.
Furthermore, the lung is closely related to the body
resistance to pathogens.
Lung-Qi Referring to the functional activities of the lung.
Meridian An important component of the human body includ-
ing the channels and their collaterals. It acts as the
important route for circulating vital energy and blood,
connecting viscerae with extremities, communicating
the upper with the lower and the interior with the
superficies, and regulating the activities of viscerae and
other parts of the body, and plays an important role
in joining the tissues and organs of the body to
build up an organic entity.
Glossary 129
Minister See Monarch, Minister, Assistant and Guide
Monarch, Minister, The terms signify the different effects of the drugs
Assistant and composed of a prescription. The Monarch acts as the
Guide chief drug for treating the disease and is composed by
one or more drugs; the Minister serves to intensify
the effect of the Monarch; the Assistant helps to deal
with the secondary symptoms or inhibits the potent
effect or toxicity of the Monarch; and the Guide leads
the other drugs to the diseased part and balances the
effects of the drugs.
Nature Also the Four Characters – referring to the property
of Chinese medicinal herbs concerning with its ther-
apeutic effect, i.e., cold, hot, warm, and cool.
Phlegm-dampness See Phlegm-wetness
Phlegm-wetness A pathogenic factor produced by prolonged reten-
tion of evil wetness in the body as a result of the
hypofunction of the spleen. It may cause a syndrome
manifested as paroxysmal and productive cough with
thin, whitish sputum, feeling of oppression over the
chest, nausea, poor appetite, enlarged tongue with
smooth and greasy fur, etc.
Qi 1) Air breathing in and out of the body during
respiration. 2) Refined and nutritious substances
flowing in the body. 3) Vital energy – the functions
of various organs and tissues of the body.
Qigong-respiratory Also Breathing exercise – A mental and physical self-
exercise training for the prevention and treatment of diseases,
and also for health care and prolongation of life,
by which life activities are self-adjusted and self-
controlled with the help of the inducement of mind
and the regulation of respiration and spirit.
Sour Sour drugs of sour taste which possess the action of
astringing or antidiarrhea.
Spleen One of the five viscerae, which, in TCM, does not
completely match the organ designated in western
medicine from the standpoint of structure, location
and function. It has the functions of digesting food,
absorbing and transporting nutrients to the body
tissues. The spleen also serves to control the blood
and to keep the blood circulating within the vessels,
and takes part in the regulation of fluid metabolism.
Some diseases of the digestive system, edema and
chronic hemorrhagic diseases are usually attributable
to malfunction of the spleen.
130 Glossary
Sthenia A syndrome occurring in a relatively strong patient
exposed to virulent evil or dysfunction of the viscera
leading to the stagnation of vital energy and blood,
phlegm-retention, indigestion, etc.; manifested as high
fever, thirst, irritability, delirium, abdominal disten-
tion, pain and tenderness, constipation, oliguria with
deep-colored urine, red tongue with rough, dry and
yellowish fur, solid and strong pulse, etc.
Superficies and U Two principal aspects for estimating the site and
interior severity of a disease. In general, a disease involving the
skin, hair and meridian is considered as a mild form of
impairment in the superficies, while those involving
the viscera as a more serious form of impairment in
the interior.
Taste Five tastes – referring to the properties of Chinese
herbs, i.e., acrid, sweet, sour, bitter and salty.
Viscerae and organs The five viscerae (Zang-organs) – a collective-name
for the heart, liver, spleen, lung and kidney. While each
of them is considered as a functional unit, the terms
for the five viscerae in TCM do not completely match
those used in western medicine. The six organs (Fu-
organs) – referring to the gall bladder, stomach, small
intestine, large intestine, urinary bladder and tri-Jiao.
Vital energy See Qi
Water and Disease due to wetness-evil – manifested as heavy feel-
dampness (disease) ing of the body, soreness of limbs, poor appetite,
diarrhea, abdominal flatulence, even edema of the
face and limbs.
Wei-Qi A kind of Yang-energy in the human body, derived
from the digestion and absorption of foods by the
spleen and stomach. Its functions include protection of
the skin and muscle, resistance against the exogenous
evils and regulation of the secretion of sweat.
Wind cold A type of common cold due to the attack of exogen-
ous wind-cold evil; manifested as fever, chilliness,
headache, anhidrosis, stuffy nose with watery dis-
charge, sneezing, cough with irritation of throat,
arthralgia, thirstlessness, thin and whitish fur on the
tongue, floating and tense pulse, etc.
Yang A philosophical term in ancient China, referring to the
things or characters opposite to Yin. The condition
which appears as active, external, upward, hot, bright,
functional, exciting and hyperactive, is attributive
to Yang. In TCM, it is widely used for explaining
Glossary 131
the physiological and pathological phenomena of the
human body, and for guiding the diagnosis and treat-
ment of diseases, for example, superficies-syndrome, heat-
syndrome, sthenia-syndrome are ascribed to Yang.
Yang deficiency A cold-syndrome in the interior resulting from the
insufficiency of Yang-energy; manifested as fatigue,
shortness of breath, intolerance of cold, cold extremit-
ies, spontaneous perspiration, pallor, polyuria with
watery urine, diarrhea, pale and tender tongue, feeble
and large or sunken and small pulse.
Yang-hyperactive A morbid condition with hyperactivity of Yang-heat,
indicative of sthenia of heat-evil while the healthy
energy of the patient is vigorous; manifested as high
fever, no sweating, noisy breathing, irritability and
thirst.
Yang-Qi Also Yang-energy. It is the opposite of Yin-energy.
As for the function and morphology, Yang-energy
stands for function. As for the physiological and
pathological phenomena, Yang-energy stands for those
which are external, upward, hyperfunctioning, rein-
forcing, light, etc.
Yin A philosophical term in ancient China, referring to
the things or characters opposite to Yang. The condi-
tion which appears as inert, internal, downward, cold,
dim, material, inhibitive and declining is attributive
to Yin. In TCM, it is widely used for explaining the
physiological and pathological phenomena of the
human body, and for directing the diagnosis and
treatment of diseases, for example, interior-syndrome,
cold-syndrome, asthenia-syndrome are ascribed to Yin.
Yin-fluid The components of body fluid belonging to Yin, such
as essence, blood, thin and thick fluid, etc.
Ying Nutrition – one of the essential substances for body
life activities. It is derived from the digested food
and absorbed by the internal organs, and circulates
through the vessels to nourish all parts of the body.
Ying-Qi Essential substance circulating in the vessels, respons-
ible for the production of blood and nourishment of
body tissues.
132 Index
Index
Abdominal distension 80 Borneol glucoside 101

Adams–Stokes syndrome 64 Borneol-glucoside-(6,1)-apioside 101
Adenosine; triphosphate 63, 86 Bornyl acetate 93
Adrenalcorticotropic hormone 88 Bradycardia 53
Aflatoxin B1 90
After-load dismatch 57 Calcium chloride 19
Alanine aminotransferase 95, 96 Campesterol 86
Alcohol precipitation 14 Camphene 93
Allergic reactions 79 Camphor 99
Alloxan 89, 102 Cancer 44
Alzheimer’s disease 34 Carbon tetrachloride 34
Amiodarone 53 Cardiac arrest 20
Amnesia; ethanol-induced 86 Cardiac arrhythmia 50
cAMP 49 Cardiac enlargement 59
Amphetamine 28 Cardiac ouput 47, 83
Anaphylaxis 79 Cardialgia 41
Anemic cardiomyopathy 60 Cardiogenic shock 20, 72
Angina pectoris 45, 47 Cardiomyopathy 54
Angiotensin II 46 Cardiovascular effects 17
Anti-atherosclerosis index 22 atherosclerosis 21
Anti-coagulase 49 cardiac arrhythmia 19
Antioxidative effects 33 contractile heart failure 18
Apical hypertrophic cardiomyopathy 61 myocardial ischemia 17
Aplastic anemia 88 shock 19
Arrhythmia; chemically induced 19; 101 toxin-induced myocardial injury 23
Assistant 2, 3 viral myocarditis 25
Atherosclerosis 21, 41 Chanigrenol 93
Atherosclerosis inducing index (AsI) 22 Chemistry
Atherosclerotic plaque 42, 44 Fructus Schisandrae 93
Atrial fibrillation 50 Radix Ginseng 82
Atropine 46, 64 Radix Ophiopogonis 98
Authentication 117 Shengmai San 5
Chest bi-syndrome 41, 43, 47
Behavioral study Chitosan 114
aggressive behaviors 26 Chloral hydrate 27
passive activities 26 Chloroform 19
voluntary mobility 26 Chlorpromazine 26
Blood clotting function 48 Cholesterol 21
Blood pressure; effects on 49; 35 Chromosomal damage;
Blood sugar level 70, 88, 89 cyclophosphamide-induced 36
Body fluid 4 Chronic obstructive pulmonary disease 73
Borneol 93, 101 Cigarette smoke 36
Index 133
Citronellyl acetate 93 Drug Rash 79
Clinical studies 41 Dyspnea 70
cardiac arrhythmia 50
cardiogenic shock 72 Eight Therapeutic Principles 1
cardiomyopathy 54 diaphoresis 2
chronic obstructive pulmonary dispelling 2
disease 73 emetic therapy 2
coronary heart disease 41 heat clearing 2
heart failure 69 invigoration 2
viral myocarditis 62 purgation 2
Clone Theory 43 reconciliation 2
Cocaine 86 warming 2
Contractility 6, 9, 47 Ejection volume 54
Coronary flow 5, 6, 8, 17, 47 Electrocardiogram 35, 45
Coronary heart disease 41 Endotoxin shock 20
Coronary spasm; pituitrin induced 9 End-systolic stress (ESS) 55
Corpus cavernosum 89 E-point septal separation (EPSS) 55, 56
Corpus striatum 29 Etiology; TCM 1
Coxsackie virus 62 Exercise-endurance 54, 55
Creatine phosphokinase 17, 45, 62, 68 Exercise-tolerance 45
Cuparene 93 Exfoliative dermatitis 79
Cyclophosphamide 36, 37, 87, 101,
102 Fatty infiltration 42
p-cymene 93 Free radicals 33, 34
Cyperene 99 Fructus Schisandrae 5, 59, 68, 71, 92
Cytochrome P-450 95, 97 chemistry 93
glycosides 94
Danseng Injection 79 lignans 93
Daucosterol 86, 95 pharmacokinetics 98
Dencichine 86 Pharmacology 95
Deoxy-ephedrine 27 anticarcinogenic effects 97
Diabetes 89 antioxidant activities 96
Dibenzo[a,c]cyclooctadiene 93 cardiovascular effects 95
Digitalis 51, 57, 69 central nervous system 95
Dilated cardiomyopathy 54, 55, 60 hepatoprotective effect 95
Diltiazem 48 physical exercise; effects on 97
Dinitrochlorobenzol (DNCB) 32 qualitative analysis 118
Diosgenin 99 quantitative analysis 124
Diuretics 51, 57, 61, 69 side effects 80
Dizziness 79 toxicity 98
DNA synthesis 24, 49, 90, 96 volatile components 93
Dobutamine 58, 59
DOPAC 29 Geraniol 93
Dopamine 57, 71 Ginsenosides 72, 86
Dopamine receptor 86 qualitative analysis 117
Dopaminergic system 29 quantitative analysis 123
Dosage forms Glucocorticoid 49, 68
capsules 112, 114, 117 Glucose-6-phosphate dehydrogenase 96
decocted paste 12 Glutathione antioxidant status 95
decoction 11, 12 Glutathione antioxidant system 34
granules 113, 115, 119 Glutathione peroxidase 34, 44, 65, 91,
injection 13, 113, 116, 120 95
powder 10, 11, 12 Glutathione reductase 95, 96
syrup 113, 115, 118 Glutathione S-transferases 95
tablets 113, 116, 120 Glycogen 18, 37, 89
tea bag 113, 115, 119 Glycosylated hemoglobin 89
tonic 112, 113, 114, 116, 118 Gomisin 96, 97, 98
134 Index
Guaiol 99 Limonene 93
Guide 2, 3 Linalool 93, 98
Lipid peroxidation 44, 45, 64, 68, 91,
Headache 79 95, 96
Heart failure 69 Liver; effects on 37
Heart function 47 Longifolene 99
Heart-blood stasis 48 Low-density lipoprotein 21, 42, 44
Heart-Qi 71 Lumbar and back myalgia 80
Hematocrit 70 Lung damage; cigarette smoke-induced
Hemodynamic changes 42 36
Hemodynamic effects 35, 55 Lung-asthenia 43
Hemorrhagic shock 19 Lymphocyte infiltration 36
Herba Ephedrae; decoction 3
High-density lipoprotein 22 Maidong see Radix Ophiopogonis
HPLC analysis Malondialdehyde 44, 64, 91, 96
ginsenosides 123 Maltol 86
methylophoppogonone 123 Methimazole 52
schisandrins 124 Methylophiopogonone 123
HVA 29 Methyltestosterone 88
5-Hydroxytryptamine 88 Microcirculation 49
Hydroxyl radical 44 Micronucleus formation 36
Hyperlipidemia 22, 90 Minister 2, 3
Hypertension 42 Monarch 2, 3
Hypertrophic cardiomyopathy 61 Monarch, Minister, Assistant and Guide 2, 9
Hypertrophy; myocardial 60 example 3
Hypnosis 27 Monoamine oxidase 31, 37
Hypotension 49 Multiple typhus 79
Mycardial cells 101
Idiopathic chest distress 79 Myocardial contractility 54
Immuno effects Myocardial energy metabolism 45
phagocytosis 32 Myocardial infarction 46, 47, 71
Immunological effects 32 Myocardial malfunction 41
anaphylaxis 33 Myrcene 93
delayed hypersensitivity 32
Inotropic action; negative 35; 47 Na+/K+-ATPase 18, 47, 101
Inotropic effect 18 Natural killer (NK) cell 86
Insomnia 79 Neural effects 26
Ischemia CNS inhibitors/stimulants 27
forebrain 86 convulsion 28
myocardial 6 mouse behavior 26, 27
Ischemia/reperfusion injury 91 neurotransmitters 29
Ischemia-reperfusion injury 34, 44 Neurasthenia 32
Isoproterenol 17, 64 Neutrophils 45
Nicotinamide 54
Jasmololone 99 Nicotine 86
Nifedipine 61
Lactate dehydrogenase 23, 37, 89 Nitric oxide synthase 87, 91
Lanatoside 70 Nitroglceride 48
Learning and memory 86 Nitroglycerin 48
Left ventricular after-load 56 Noradrenergic system 31
Left ventricular diastolic function 47
Left ventricular functions 54 Open-heart surgery 45
Left ventricular systolic functions 54 Ophiopogon japonicus see Radix
Leukopenia 37 Ophiopogonis
Leukopenia; cyclophosphamide Ornithine decarboxylase 96
induced 101 Oryzanol 52
Levamisole 32, 33 Ouabain 17
Index 135
Paeonol 21 antineoplastic effects 90
Palpitation 47 antioxidant activities 91
Panax Ginseng see Radix Ginseng cardiovascular effects 87
Panaxadiol central nervous system 86
qualitative analysis 117 endocrine 88
Panaxans 85 hematopoietic effects 88
Panaxatriol immunomodulatory effects 86
qualitative analysis 117 metabolism; effects on 89
Panaxydol 85 polysaccharides 85
Panaxynol 85 qualitative analysis 120
Panaxytriol 85 quantitative analysis 122, 123
Parkinson’s disease 34 saponins 82
Passive cutaneous anaphylaxis 33 side effects 80
Pathogenesis 1 sugars 85
Pentetrazole 28 Toxicity 92
Pentobarbital 18, 27, 35 volatile components 85
Peripheral vascular resistance 47 Radix Ginseng Destillata
Pharmacology side effects 79
Fructus Schisandrae 95 Radix Glycyrrhizae 3
Radix Ginseng 86 Radix Ophiopogonis 4, 59, 68, 71, 98
Radix Ophiopogonis 101 chemistry 98
Shengmai San 5, 16 flavanoids 99
Physicochemical analyses 117, 118, 119, Pharmacology 101
120, 121 anti-hypoxic effect 101
Pinene 93 antitussive effect 102
Pituitrin 17 cardiovascular effect 101
Platelet activating factors 48 hypoglycemic effect 102
Platelet aggregation 21, 42, 49, 87 immunomodulatory effect 101
Polymorphonuclear qualitative analysis 117, 121
leukocytes 45 quantitative analysis 123
Prednisone 37 saponins 99
Pregomisin 93 side effects 79, 80
Premature beat 51 toxicity 102
Primordial-Qi; deficiency of 62 volatile oils 99
Proencephalon 30, 31 Ramulus Cinnamomi 3
Propranolol 61 β-Receptor blockers 57
Prostacyclin 49 Renshen see Radix Ginseng
Prothrombin 49 Respiratory effects 35
Protopanaxadiol 86, 90 Ribavirin 63
Protopanaxatriol 86, 92 RNA biosynthesis 90
Pulmonary emphysema 37 Ruscogenin 99
Pump functions 54
Salicymide 86
Qi and Yin deficiency 57 Sapogenins see Saponins
Qi-deficiency 16, 43 Saponins 57
Quality control 116 oleanolic acid type 83
protopanaxdiol type 83
Radix Codonopsis protopanaxtriol type 84
qualitative analysis 120 qualitative analysis 122
Radix Ginseng 4, 57, 58, 68, 71, 82 Radix Ginseng 82
acetylenic compounds 85 Radix Ophiopogonis 98
chemistry 82 Schisahenol; qualitative analysis 121
microscopic examination 119 Schisandrins 72
peptide glycans 85 Schisandrins; quantitative analysis 123
pharmacokinetics 92 Semen Armeniacae 3
Pharmacology 86 Serotonin 30
adaptogenic effects 91 Serotoninergic system 30
136 Index
Shengmai San Tachycardia 50
current use of 10 Terpinen-4-ol 93, 99
traditional use of 4, 10, 16 Tetrodotoxin 89
traditional use of 43 Thin-layer chromatography 123
antioxidative effects 33, 34 Thrombosis 42, 48
blood pressure; effects on 35 Thromboxane 49
cardiovascular effects 16 Thymol methylether 93
clinical effects 10 Total peripheral resistance (TPR) 57
clinical studies 41 Toxins; effects on 36
dilated cardiomyopathy; Treatment by Differentiation of Signs
treatment of 54 and Symptoms 1
dosage forms 10, 114
hemodynamic effects 35 Ultracentrifugation 114
immuno effects 32 Ultrafiltration 115
neural effects 26 Urokinase 46
pharmacology 16
preparations 112 Vasopressive amine 49
pump function; effect on 70 Ventricular arrhythmia 59
quality control 116, 122 Ventricular diastolic dysfunction 47
rationale of formulation 4 Ventricular fibrillation 19
respiratory effects 35 Ventricular late potential (VLP) 52
side effects 78 Verapamil 61
toxin; effects on 23 Very low-density lipoprotein 42
viral myocarditis; treatment of 62, 63 Viral myocarditis 62
Side effects; extrinsic 79 diagnosis 62
Side effects; intrinsic 79 pathogenesis 62
SMS injection 60 Viral treatment 63
Sorbitol dehydrogenase 37 Vitamin A 101
Stagnation of phlegm-dampness 52
Stigmasterol 86, 94 Wuweizi see Fructus Schisandrae
Stroke volume 55
Strychnine 29 Yang depletion 60
Superoxide dismutase 64, 91 Yang hyperactivity 79
Superoxide radical 44 Yin depletion 60
Sympathomimetic drugs 72 Yin-deficiency 16, 43
Systemic vascular resistance (SVR) 55 Yin-fluid depletion 43

LIBRO - Shengmai San

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

LIBRO - Shengmai San

Uploaded by

Copyright:

Available Formats

Shengmai San

Traditional Herbal Medicines for Modern Times

Edited by Dr Roland Hardman

Kam-Ming Ko, Hong Kong University of

London and New York

© 2002 Taylor & Francis

ISBN 0-203-21645-8 Master e-book ISBN

ISBN 0-203-27265-X (Adobe eReader Format)

1 Shengmai San – a renowned traditional Chinese medicinal formula 1

2 Pharmacological studies on Shengmai San 16

3 Clinical studies on Shengmai San 41

4 Side effects of Shengmai San 78

5 Phytochemistry and pharmacology of component herbs of

6 Contemporary applications of a traditional formula:

Bao-Jing Lu Liang-Yuan Zheng

Kam-Ming Ko Si-Qian Liang

Tze-Kin Yim Zhi-Min Xu

Kam-Ming Ko, Ph.D.

1 Shengmai San – a renowned

THE THEORY OF TRADITIONAL CHINESE MEDICINE

I. Treatment by differentiation of signs and symptoms

II. The eight therapeutic principles

III. The monarch, minister, assistant and guide of herbal formulas

IV. Example of a TCM prescription

THE ORIGIN OF SHENGMAI SAN – THE RATIONALE OF

CHEMICAL AND PHARMACOLOGICAL STUDIES ON THE

I. Effects of SMS and its individual herbal component in

A. Effects on coronary ﬂow (Figure 1.1)

B. Effects on myocardial contractility (Figure 1.2)

A. Effect on coronary ﬂow (Figure 1.3)

Error 48 4951.2 103.2

B. Effect on myocardial contractility

SMS-RELATED FORMULATIONS AND THEIR CLINICAL

I. Modiﬁed Shengmai powder

II. Shengmai drink

IV. Cold decoction of Radix Ophiopogonis (Maimendong Yinzi)

VI. Ginseng-Astragali powder

VIII. Ginseng-Astragali powder

IX. Decoction for ﬂaccid limbs (Wuwei Tang)

X. Decocted paste of Polygonati essence (Yuhua Jian)

XII. Ginseng injection

XIII. Ginseng-Ophiopogonis injection

XIV. Astragali-Shengmai drink

XV. Treasure for preserving youth (Qingchun Bao)

XVI. Hypoglycemic agent (Taizi Bao) (experimental formula)

XVII. Tonic for beneﬁting the heart (Zhenqi Fuzheng Tang)

Anonymous (1186) Origin of Medicine.

A. Effect on pituitrin-induced changes in coronary ﬂow in isolated rat hearts

B. Effect on isoproterenol-induced myocardial damage in rats

II. Contractile heart failure

A. Effect on pentobarbital-induced contractile heart failure in dogs

B. Effect on pentobarbital-induced contractile failure in isolated rat hearts

C. Effect on pentobarbital-induced acute contractile failure in

III. Cardiac arrhythmia

A. Effect on cardiac arrhythmia induced by electrical stimulation on

B. Effect on ventricular ﬁbrillation induced by chloroform in mice

C. Effect on cardiac arrhythmia induced by calcium chloride in rats

D. Effect on cardiac arrhythmia induced by electrical stimulus to isolated

(1) Effect on hemorrhagic shock in rabbits

(2) Effect on hemorrhagic shock in dogs

(3) Effect on ischemia-induced acute cardiac arrest in rats

(1) Effect on endotoxin-induced shock in rabbits

(2) Effect on endotoxin-induced shock in mice

(1) Effect on acute heart dysfunction in rabbits