Accepted Manuscript Title: Artemisia campestris L.: Ethnomedicinal, phytochemical and pharmacological review Author: Ikram Dib Luc Angenot Atika Mihamou Abderrahim Ziyyat Monique Tits PII: DOI: Reference: S2210-8033(16)30083-5 http://dx.doi.org/doi:10.1016/j.hermed.2016.10.005 HERMED 158 To appear in: Received date: Revised date: Accepted date: 18-5-2015 19-10-2016 19-10-2016 Please cite this article as: Dib, Ikram, Angenot, Luc, Mihamou, Atika, Ziyyat, Abderrahim, Tits, Monique, Artemisia campestris L.: Ethnomedicinal, phytochemical and pharmacological review.Journal of Herbal Medicine http://dx.doi.org/10.1016/j.hermed.2016.10.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Artemisia campestris L.: Ethnomedicinal, phytochemical and pharmacological review Ikram Diba, Luc Angenotb, Atika Mihamouc, Abderrahim Ziyyata* and Monique Titsb a Laboratoire de Physiologie et Ethnopharmacologie URAC-40, Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda-Maroc b Phytochimie et Phytothérapie, Laboratoire de Pharmacognosie, Département de Pharmacie, Université de Liège, Belgique c Laboratoire de Biologie des Plantes et des Microorganismes, Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda-Maroc * Corresponding author : Pr Abderrahim ZIYYAT Laboratoire de Physiologie et Ethnopharmacologie, Département de Biologie, Faculté des Sciences, Université Mohamed Premier, Oujda - Maroc Phone: + (212) 6 67 08 61 22 Email 1: ziyyat@fso.ump.ma Email 2 : ziyyat@yahoo.fr 1 Artemisia campestris L.: Ethnomedicinal, phytochemical and pharmacological review Ikram Diba, Luc Angenotb, Atika Mihamouc, Abderrahim Ziyyata* and Monique Titsb a Laboratoire de Physiologie, Génétique et Ethnopharmacologie URAC-40, Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda-Maroc b Laboratoire de Pharmacognosie, Département de Pharmacie, Université de Liège, Belgique c Laboratoire de Biologie des Plantes et des Microorganismes, Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda-Maroc * Corresponding author : Pr Abderrahim ZIYYAT Laboratoire de Physiologie, Génétique et Ethnopharmacologie – URAC 40, Département de Biologie, Faculté des Sciences, Université Mohamed Premier, Oujda Maroc Phone: + (212) 6 67 08 61 22 Email : ziyyat@yahoo.fr 2 Abstract Artemisia campestris L. (Asteraceae) is a perennial herb, commonly known as field wormwood. It is widespread in Asia, North America, Europe and North Africa. The different parts of this plant are used as anthelmintic, antidiabetic, antihypertensive, emmenagogue, antivenom, and to treat digestive and cutaneous problems. An exhaustive bibliographic research of this plant has been carried out by means of scientific engines and databases like Google Scholar, PubMed, Science direct and SciFinder; as a result, it has been found that this herb possesses a rich phytochemical content and a wide range of pharmacological activities such as antioxidant, insecticidal, antibacterial, antimutagenic, antivenom and antitumor effects. In an aim to highlight the importance of A. campestris L., this review has been established by discussing its ethnomedicinal, morphological, ecological, phytochemical, pharmacological and toxicological studies. Key words: Artemisia campestris L., Ethnomedicine, Ecology, Phytochemistry, Pharmacology. 3 Table of contents Abstract ......................................................................................................................................... 3 1. Introduction ......................................................................................................................... 6 2. Methodology ....................................................................................................................... 6 3. Morphological description of Artemisia campestris L........................................................ 7 4. Ethnomedicinal uses of Artemisia campestris L. ................................................................ 9 5. Eco-geographical features of Artemisia campestris L. ..................................................... 10 Phytochemistry of Artemisia campestris L. ................................................................................ 11 6. 5.6. Flavonoids ................................................................................................................... 11 5.6. Phenolic acids.............................................................................................................. 13 5.6. Coumarins and isocoumarins ...................................................................................... 14 5.6. Other compounds ........................................................................................................ 14 5.6. Volatile compounds..................................................................................................... 15 Pharmacology of Artemisia campestris L. ........................................................................ 20 6.1. Antioxidant activity ..................................................................................................... 20 6.1.1. DPPH (diphenyl picrylhydrazyl) radical scavenging activity ............................. 20 6.1.2. ABTS+ (2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) free radical scavenging activity............................................................................................................ 21 6.1.3. Other in-vitro antioxidant effects ........................................................................ 22 6.2. Antibacterial activity ................................................................................................... 23 6.3. Antifungal activity....................................................................................................... 25 6.4. Insecticidal activity ..................................................................................................... 26 6.5. Anthelmintic activity ................................................................................................... 27 6.6. Antitumor activity ....................................................................................................... 27 6.7. Antihypertensive effect ............................................................................................... 28 7. Toxicology of Artemisia campestris L.............................................................................. 29 8. Conclusion and perspectives ............................................................................................. 29 Conflict of interest....................................................................................................................... 30 4 Acknowledgements ..................................................................................................................... 30 References ................................................................................................................................... 31 5 1. Introduction Artemisia campestris L. is an Asteraceae species, with a large distribution in the northern hemisphere; it displays a wide repartition in Eurasia and predominates the arid regions of North Africa. Artemisia campestris has many medicinal actions, including: antivenom, anticancer, antidiabetic, antihypertensive, anthelmintic, antimicrobial, antifungal, and has been utilized in treating many other conditions, including: digestive, respiratory, cutaneous and genital diseases. The phytochemical profile of A. campestris L. has shown abundance in flavonoids, phenolic acids, coumarins, isocoumarins, fatty acids, as well as a high content of monoterpenes and sesquiterpenes contained in the essential oil. The pharmacological activities spans a wide range of potentials uses such as antioxidant, antifungal, insecticidal, antibacterial, antimutagenic, antitumor, anthelmintic and antihypertensive. The information above is fully referenced in the body text. This review gives a detailed insight about the species A. campestris L. that covers its botany, folk-medicinal uses, ecology, phytochemistry, pharmacology and toxicology. 2. Methodology A comprehensive bibliographic research was conducted to give an in-depth insight into the medicinal plant A. campestris L. and its related subspecies. Our literature research has been carried out by means of the scientific engine Google Scholar (http://scholar.google.com), and via (http://www.ncbi.nlm.nih.gov/pubmed), Scopus Direct (http://www.sciencedirect.com), the databases, PubMed (http://www.scopus.com), Science and SciFinder (http://www.libnet.ulg.ac.be/en/eresources/scifinder-scholar). This review investigates 6 the ethnomedicinal, morphological, ecological, phytochemical, pharmacological and toxicological studies reported on A. campestris L. The references compiled in this review contain 103 papers, including 94 original articles, 2 review articles, 3 books and 4 books references, dating from 1863 until July 2015. All full texts and informative abstracts of studies dealing with A. campestris L. have been retained, among which 10 documents that have been written in French (6 articles and 4 books), while the remainder of citations are in English. Unpublished thesis works and congresses communications have been excluded. The chemical structures have been revised by consulting the open chemistry database PubChem (http://pubchem.ncbi.nlm.nih.gov/search/#collection=compounds), and then redrawn using the freeware version of the software ACD/ChemSketch (Freeware) 14.01. (Chemical structures available in supplementary data on-line) 3. Morphological description of Artemisia campestris L. A. campestris L. is a perennial undershrub, that may reach 30-150cm in height, with branched and ascending stems that form a panicle shape; it is usually brownish-red and glabrous, and acquires a lignified form in the inferior part and a pubescent one at the top (Chalchat et al. , 2003; De Lamarck and De Candolle, 1815; Quézel and Santa, 1962). The leaves are green, sericeous when young, often glabrescent when mature; the basal leaves are 2-3 pinnatisect, petiolate or even auricled, the upper are most simple. (Chalchat et al., 2003; Quézel and Santa, 1962) (Fig.1A and 1B). The plant has a composed inflorescence: the capitulum (Fig. 1C), ovoid and heterogameous, containing 8 to 12 flowers, organized on convex and glabrous receptacles, and surrounded by involucral glabrous bracts organized in several rows. The ray flowers are female, pistillate and fertile, while the disk flowers are sterile, and functionally male with 7 reduced abortive ovaries (Chalchat et al., 2003; Gillet and Magne, 1863; Ouyahya, 1990; Quézel and Santa, 1962). The male flowers are tubular, yellowish, lacking calyx, with 5 fused petals, and 5 fused stamens, with the presence of secretory sacs on corolla lobes of disk flowers (Minami et al. , 2010). The fruit is an ovoid achene lacking pappus (Kreitschitz and Vallès, 2007). According to Tutin et al. (1976) A. campestris L. is a polymorphic species and is segregated into six subspecies that can be distinguished by morphological and karyological data: Artemisia campestris (a) Subsp. campestris L., (b) Subsp. glutinosa (Gay ex Besser) Batt., (c) Subsp. maritima Arcangeli; (d) Subsp. borealis (Pallas) Hall & Clements; the main subspecies’ discussed in this paper are Subsp campestris, glutinosa and maritima since they are the most studied subspecies in the literature. (a) Subsp. campestris L.: is distinguished by a glabrescent stems and leaves, fleshy and keeled beneath leaf-lobes which are thinly lanate when young, wide panicle, shortly pedunculate capitula with an involucre width 1.5-2.5 mm, rarely hairy. The cytotype of this subspecies is 2n=36 (D'Andrea et al. , 2003). The other subspecies have the same characteristics as Subsp. campestris L. with some differences; for (b) Subsp. glutinosa (Gay ex Besser) Batt., the panicle-branches and involucral bracts are viscid, besides, the capitula are sessile or subsessile, but like (a), the cytotype is 2n=36 (Bellomaria et al. , 2001). Concerning (c) Subsp. maritima Arcangeli, the morphological differences consist of a fleshy but not keeled beneath leaf-lobes with a convex shape, and with a velutinous aspect when young, also the capitula are often curved. For this subspecies the main difference is the karyological number which is estimated as 2n=54 (Kreitschitz and Vallès, 2003). The Subsp. borealis (Pallas) Hall & Clements (d), are without fleshy 8 leaf-lobes, with an involucre width of 5-6mm and the outer bracts almost entirely herbaceous. The cytotype is 2n= 18 or 36. 4. Ethnomedicinal uses of Artemisia campestris L. A.campestris L. is commonly used as an anthelmintic and a treatment for cutaneous, respiratory and digestive problems in many countries like Morocco, Algeria, Tunisia, Libya, Spain, Turkey, Italy, Serbia, India, Argentina, Canada and United States (Ben Sassi et al. , 2007; Boulanouar et al. , 2013; De Natale and Pollio, 2012; El Hassani et al. , 2013; Fakchich and Elachouri, 2014; Gast, 1989; Hammiche and Maiza, 2006; Kujawska and Hilgert, 2014; Leporatti and Ghedira, 2009; Popović et al. , 2012; Shemluck, 1982; Tlili et al. , 2013). It is used as an antidiabetic and antihypertensive in Morocco, Algeria and Japan (Aniya et al. , 2000; Ben Sassi et al., 2007; Bnouham et al. , 2002; Boudjelal et al. , 2013; Djidel et al. , 2009), and is used to treat urinary, kidney and liver disorders in Japan, Algeria and Tunisia (Aniya et al., 2000; Ben Sassi et al., 2007; Benchelah et al. , 2004; Ferchichi et al. , 2006; Minami et al., 2010). It has an extensive use as an emmenagogue and as a circulation regulator, especially in postpartum care, in Algeria (Benchelah et al., 2004; Boulanouar et al., 2013; Gast, 1989; Hammiche and Maiza, 2006) and Serbia (Benítez et al. , 2010; Popović et al., 2012). Furthermore, it is used as a febrifuge in Algeria (Boulanouar et al., 2013), Tunisia (Ben Sassi et al., 2007) and Italy (Guarino et al. , 2008) and is utilized as an anti-venom in Tunisia (Ben Sassi et al., 2007) and India (Bahekar et al. , 2012). It possesses other traditional actions, such as anti-inflammatory and tonic (Ben Sassi et al., 2007; Popović et al., 2012), as an analeptic (Hammiche and Maiza, 2006) and it is also recommended in the treatment of eye diseases (El Hassani et al., 2013) (Table 1). 9 5. Eco-geographical features of Artemisia campestris L. Ecologically, A. campestris L. is able to thrive in an extremely large range of ecological habitats, from thermo- Mediterranean scrub to mountainous belts and from Saharan to humid zones (Subally and Quézel, 2002); it was also reported, that this species can be found in the Supra-mediterranean bioclimatic storey upwards (Cariñanos et al. , 2013). It prefers open habitats like meadow, forest glades and forest edges, and grows mainly on dry soils (Nobis et al. , 2014). In fact, it was described that A. campestris L. occurs in different forms depending on its habitat and ecotypes; as a result, four forms were identified; (i) a shifting dune form related to the dune ecotype, (ii) a salty form that grows in the salt meadows along the coast, (iii) a field form present in dry pastures and gravelly field, and finally, (iv) a calcareous form that exists in the calcareous rock fields and barren grounds (Turesson, 1925). Its occurrence is in fact conditioned by edaphic rather than climatic criteria (Subally and Quézel, 2002). Geographically, A. campestris L. predominates in the arid regions of North African countries (Noumi et al. , 2010) like Morocco (Fakchich and Elachouri, 2014), Algeria (Rebbas and Bounar, 2014), Tunisia (Kawada et al. , 2012; Saadaoui et al. , 2014), and Libya (El-Mokasabi, 2014). It grows in dry, base-rich grasslands throughout much of Central and Southern Europe (Pirini Chrisoula et al. , 2014); it is considered a ruderal plant, in the disturbed dry river lands of Southern Spain (Salinas and Guirado, 2002). It accompanies the dominant vegetation in xerophilous grasslands in the Czech Republic (Novák and Konvička, 2006) and grows on gravelly soils near the rivers Tammaro and Calore in Italy (Guarino et al., 2008), while, in Japan, it grows wild along the coastline of the Ryukyu Islands (Minami et al., 2010). It represents the native forb species that persists in reference sites of restored dunes in Great Lake in North America (Emery and 10 Rudgers, 2010). It is noteworthy to mention that A. campestris L. subspecies have different geographical distribution. D'Andrea et al. (2003) reported that the Subsp. campestris have a wide range of distribution in Europe, Northern and Central Asia and North Africa, while, the Subsp. glutinosa seems to be limited to Europe, from Siberia to Great Britain and in northern Africa (Juteau et al. , 2002; Masotti et al. , 2012). This subspecies has also been described by Le Houerou (2013) as a dwarf shrub that belong to steppes of the arid and desert zone of the near east and north Africa. The subspecies maritima predominates the maritime sands of all the European Atlantic coast and northwards to the Netherlands (Kreitschitz and Vallès, 2003; Tutin et al., 1976), and the subspecies borealis exists mainly in the Alps and Arctic Russia (Tutin et al., 1976). Phytochemistry of Artemisia campestris L. 5.6. Flavonoids A. campestris L. consists of many taxa, among which the subspecies glutinosa, campestris and maritima, that have been profoundly studied for their flavonoid profile. It has been reported that A. campestris L. contained a high amount of flavones, such as: chrysin, apigenin, 6-methoxyapigenin (hispidulin),7,4’-O-dimethyl apigenin, 7-Omethyl 8-hydroxyapigenin, 7-O-methyl 6-methoxyapigenin (cirsimaritin), 4’-O-methyl 6-methoxyapigenin, 7-O-hexoside apigenin, 6,8-di-C-glucoside glucuronide apigenin, 6-C-glucuronide 8-C-pentoside apigenin, apigenin, 7-O- linderoflavone B, ficine, isoficine, luteolin, 6-methoxyluteolin (eupafolin), 7-O-methyl6-methoxyluteolin (cirsiliol), 7,3’-O-dimethyl 6-methoxyluteolin (cirsilineol), 7,4’-O-dimethyl 6- methoxyluteolin (eupatorin), 7,3’,4’-O-trimethyl 6-methoxyluteolin, acetylglucuronide, glucoside 6-methoxyluteolin (eupafolin glucoside) and 7-O-rutinoside luteolin. On the other hand, the flavonols subclass seems to be represented mainly by kaempferol and its 11 derivatives: 7-O-methyl kaempferol, 3,7,-O-dimethyl kaempferol, 3,7,4’-O-trimethyl kaempferol, 3,7,4’-O-trimethyl 6-methoxykaempferol, 3-rhamnoside kaempferol, 3rutinoside kaempferol, (quercetagetin), by quercetin and its 3’-O-methyl quercetin derivatives: (isorhamnetin), 6-hydroxyquercetin 7-O-methyl quercetin (rhamnetin), 4’-O-methyl quercetin (tamarixetin), 3,3’-O-dimethyl quercetin, 3-Omethyl 6-methoxyquercetin (axillarin), 3-O-glucuronide quercetin, 3-rutinoside quercetin (rutin), 3-galactoside quercetin (hyperoside), 3’-O-methyl hexoside quercetin, and by myricetin and its derivatives: 3’-O-methyl myricetin (laricitrin), 4’-O-methyl myrecitin (mearnsetin), and 3’,4’-O-dimethyl 6-methoxymyricetin (Akkari et al. , 2014; Djeridane et al. , 2007; El-Ghazouly and Omar, 1984; Karabegović et al. , 2011; Megdiche-Ksouri et al. , 2015; Sebai et al. , 2014). Only the dihydroflavone hesperidin has been reported to exist in A.campestris L., while the 7-O-methyl taxifolin was the only representative of the dihydroflavonols sub-class (Akkari et al., 2014). For A. campestris subsp. glutinosa, in the acetone extract of the aerial part, the flavones chrysin, apigenin, 7-O-methyl apigenin, 6-methoxyapigenin (6-O-methyl scutellarin or hispidulin), luteolin, 6-hydroxyluteolin and 7,4’-O-dimethyl 6-methoxyluteolin have been identified (De Pascual Teresa et al. , 1986; Valant-Vetschera et al. , 2003), instead, 6-methoxyapigenin (hispidulin) has been found in the chloroformic extract of the flowering tops and the chloroform extract of the aerial part (De Pascual Teresa et al., 1986; Hurabielle et al. , 1982). Other authors reported the existence of flavonols in the hexane extract of this plant, like, 7-O-methyl kaempferol, quercetin, 3-O-methyl quercetin, 7-O-methyl quercetin (rhamnetin), 7, 3’-O-dimethyl quercetin, (De Pascual Teresa et al., 1986; 1984; González et al. , 1983; Valant-Vetschera et al., 2003). In the acetone, hexanic and chloroformic extracts of the aerial part or the flowering tops, eight 12 dihydroflavones have been identified, being, dihydrochrysin (pinocembrin), 7-O-methyl dihydrochrysin (pinostrobin), naringenin, 7-O-methyl naringenin (sakuranetin), 4'-Omethyl naringenin (isosakuranetin), 7,4'-O-dimethyl naringenin, eridictyol, 7-O-methyl eriodictyol, 3’-O-methyl eriodictyol (padmatin) and 7, 3’-O-dimethyl eriodictyol (De Pascual Teresa et al., 1986; 1984; González et al., 1983; Hurabielle et al., 1982; ValantVetschera et al., 2003). Further studies confirmed the presence of 7-O-methyl aromadendrin, 7-O-methyl taxifolin, 7, 3’-O-dimethyl taxifolin and 7, 4’-O-dimethyl taxifolin as the principal dihydroflavonols (Hurabielle et al., 1982; Valant-Vetschera et al., 2003). In A. campestris subsp. maritima, the flavone 6-methoxyapigenin (hispidulin) and the dihydroflavonol 7,3’-O-dimethyl taxifolin were isolated from the chloroformic extract of the aerial part (Rauter et al. , 1989). However, the acetone and chloroformic extracts seem to contain mainly the dihydroflavones: 5,8,4’-trihydroxyflavanone, 5,6-dihydroxy 4’-methoxyflavanone, naringenin, 7-O-methyl naringenin (sakuranetin), 4’-O-methyl naringenin (isosakuranetin), eriodictyol, 7, 3’-O-dimethyl eriodictyol and 7, 4’-Odimethyl eriodictyol (Rauter et al., 1989; Vasconcelos et al. , 1998). About A. campestris subsp. campestris, the flavonoid patterning was less complicated with the only subclass of flavonols that was represented by the compounds 3,4’-O-dimethyl kaempferol (ermanin), 3,4’-O-dimethyl 5’-methoxykaempferol and 3’-O-methyl quercetin (isorhamnetin) found in the cyclohexane, ethyl acetate and dichloromethane extracts of the aerial part (Ferchichi et al., 2006) (Fig. 2, 3 and 4: see supplementary data on-line)). 5.6. Phenolic acids Riedel et al. (2010) found that the cells in culture obtained from seed germination of A. 13 campestris L. are rich in phenolic compounds such as chlorogenic acid, trans ferulic acid, 4-methoxy-cinnamic acid, vanillic acid and isochlorogenic acids A, B and C. These findings are in accordance with other studies conducted on phenolic rich extract of A. campestris L. from Algeria and on methanolic, water and ethyl acetate extracts of the aerial part of Tunisian A. campestris L. which found that these preparations contained chlorogenic and caffeic acids as well as isochlorogenic acids A, B and C (Djeridane et al., 2007; Megdiche-Ksouri et al., 2015; Sebai et al., 2014) (Fig.5). It is of interest to note that phenolic content is highly sensitive to the measuring method (Boulanouar et al., 2013), and the phenol content measured by Folin-Ciocalteu of the Algerian A.campestris L. was lower than those reported by other authors (Djeridane et al., 2007; Djidel and Khennouf, 2014; Karabegović et al., 2011; Megdiche-Ksouri et al., 2015). 5.6. Coumarins and isocoumarins According to Naili et al. (2010) and Masotti et al. (2012), leaves of A. campestris L. do not contain coumarins. However, other studies have clearly shown the existence of coumarin and its derivatives in several extracts of A. campestris L. including hydroxycoumarins, esculetin, iso-fraxidin, fraxidin, scopolin, herniarin, scopoletin (González et al., 1983; Megdiche-Ksouri et al., 2015; Vasconcelos et al., 1998). In addition, three isocoumarins were isolated from A. campestris subsp. campestris: artemidinal, E-artemidin and (+) epoxyartemidin (Ferchichi et al., 2006) (Figure 5: see supplementary data on- line). 5.6. Other compounds The hexane extract of the leaves of A. campestris L. showed a high amount of fatty acids, which the most important are, linoleic acid α-linolenic acid and palmitic acid 14 (Carvalho et al. , 2011). Petunidin-3-O-acetyl glucoside was the first and only anthocyanin contained in the methanolic extract of the aerial part of A.campestris L. from Tunisia (Megdiche-Ksouri et al., 2015). 5.6. Volatile compounds The species A. campestris L. can be subdivided into several chemotypes, which can be classified according to the variability of their volatile fractions, which vary between different populations growing in various localities. The main components which predominate in the essential oil and extracts of this plant seem to be common to almost all the subspecies of A. campestris L. (Figure 6: see supplementary data on-line). Tunisia: The essential oil of the aerial part of A. campestris L., analyzed in 4 different localities from Southern Tunisia and over different phenologic stages, has been found to be more abundant in sesquiterpenes (66-93%), with a weaker content of monoterpenes (529.8%). The main terpenes found are: ß-pinene (24-49.8%), p-cymene (2.3-22.3%), αpinene (4.1-12.5%), camphor (10.3%), spathulenol (1.2-10%), γ-muurolene (0.5-9.6%), limonene (4.9-9.3%), germacrene D (7.3 %), (ar)-curcumene (6.9%), α-cubebene (6.6%), γ-terpinene (2.2-6.5%), β-eudesmol (1-6.4%), myrcene or β- myrcene (1.4-6%), (Z)-ß-ocimene (1.8-5.5%), geranyl acetate (5%), (E)-ß-ocimene (4.3%) and (Z)-βfarnesene (2.9- 4.2%) (Akrout et al., 2011, 2010, 2007, 2003, 2001). Additional analysis showed that essential oil of the subspecies glutinosa growing in Tunisia was rich in βpinene (41.1%), p-cymene (9.9%), α-terpinene (7.9%), (Z)-β-ocimene (6.7%), limonene (6.5%) and myrcene (4.1%) (Aicha et al., 2008). Moreover, menthol and artemisinic acid have been found in the ethyl acetate and methanolic extracts of A.campestris L. 15 from Tunisia (Megdiche-Ksouri et al., 2015). Algeria In Algeria, little variability has been found in essential oils obtained from A. campestris L. growing in two different regions, which were rich in monoterpenes (84.5-91.7%), while the total of sesquiterpenes were estimated as (5.1%-7.2%). The major components of A. campestris L. have been identified as β-pinene (25.6%), α-Terpenyl acetate (18.8%), α-pinene (18.4%), sabinene (17%), (Z, E)-farnesol (10.3%), camphor (9.2%), camphene (7.7%), limonene (6.6%), cedrol (5.4%), borneol (5.2%), p-cymene (4.1%), and verbenone (3.8%) (Belhattab et al. , 2011; Boulanouar et al., 2013; Dob et al. , 2005). Spain In a study conducted by De Pascual Teresa et al. (1983), the hexane extract from the leaves of the Spanish A. campestris L. contained the sesquiterpenes: phytol, spathulenol and β-eudesmol. Portugal The analysis of A. campestris subsp. maritima essential oil from Portugal afforded the identification of 31 terpenic compounds; the most abundant compounds were: β-pinene (17.8%) and cadin-4-en-7-ol (16.4%), γ-terpinene (8.7%), cis-β-ocimene (7.4%), aromadendrene (6.7%), δ-cadinene (5.1%) and limonene (4.2%) (Silva et al. , 2002; Silvestre et al. , 1999). France In France, the comparison between the different phenological stages of A. campestris 16 subsp. glutinosa showed that the essential oil composition was quite similar between the various stages; with as main components: γ-terpinene (20.8-46.5%), capillene (8.933.1%), 1-phenyl-2,4-pentadiyne (16.2-29.7%), spathulenol (11.3%), O-methyleugenol (4.5-6.6%), 1-phenyl-2,4-pentadiynone (6%) and p-cymene (4.5%). However, it should be noted that γ-terpinene was more abundant in the vegetative stage, while capillene was more quantified during the seed stage (Juteau et al., 2002). Another screening of the volatile composition of the ethanolic extract obtained from the aerial part of A.campestris subsp. glutinosa occurring in France showed the presence of the major components: capillene (49.1%), γ-terpinene (23%) and 1-phenylpenta-2,4-diyne (18.1%) (Masotti et al., 2012). Italy In Italy, the essential oil composition of three varieties of A. campestris L. has been determined. The first study reported the seasonal composition of A. campestris subsp. glutinosa, and the major compounds characterized were β-pinene (6.9-57.2%), germacrene D (5.9-28.6%), bicyclogermacrene (3.9- 14.5%), myrcene (3.8- 11.2%), αpinene (5.3-9.2%), α-bisabolol (3.2-7%), methyl eugenol (3.7-6.9%), limonene (46.7%), spathulenol (4.1-6.6%), viridiflorol (4.1-6.6%), (E,E)-α-farnesene (5-5.9%), (E)β-ocimene (4.9-5.4%) and α-humulene (4.8%) (Bellomaria et al., 2001). The second analysis carried out on A. campestris subsp. borealis, highlighted the presence of the caryophyllene oxide (18.2%) as the main component, followed by α-pinene (15.3%), βpinene (9.8%), spathulenol (9.3%), 2, 3-dihydro-1,8-cineole (5.2%), limonene (4.9%) and pinocarveol (3.8%) (Mucciarelli et al. , 1995). Poland 17 A comparative study of the volatiles contained in the essential oils of the different parts of A. campestris subsp. campestris from Poland showed a new major compound (Z)falcarinol (19-38.8%), that mainly existed in the stem and roots, followed by germacrene D (9.7-28%) in the inflorescences, flowers, leaves and stems parts. The remaining major compounds: γ-humulene (4-8.2%), (E)-ß-caryophyllene (4.1-6.5%), Germacra-4(15),5,10(14)-trien-1α-ol (4.2-5.5%), (E,E)-α-Farnesene (3.5-4.3%), were similarly distributed in the inflorescences, flowers, stems and leaves. In this subspecies, the sesquiterpenes predominate (38.7-76.7%) the monoterpenes (7-19.8%) (Lis and Kowal, 2015). Lithuania The essential oil profiling of A. campestris subsp. campestris from different parts of Lithuania showed different profiles of the essential oils with the presence of caryophyllene oxide (3.7-38.8%), germacrene D (3.8-31.2%), γ-curcumene (4-14.8%), β-pinene (3.9-13.8%), α-pinene (4-11.4%), humulene epoxide II (3.7-11.7%), β-silene (6.5-10.8%), β-caryophyllene (3.8-10%), spathulenol (4-9.7%), (E,E)-α-farnesene (5.79.4%), β-ylangene (3.7-8.3%), β-elemene (3.8-7.6%), eudesma-4(15),7-dien-1β-ol (0.17.1%), junenol (4.6-6.1%), cis-pinane (6%), (Z)-β-farnesene (3.8-5.6%), α-cadinol (4.17.4%), germacra-4(15),5(10),14-trien-1α-ol (4-6.3%), α-humulene (5%), limonene (5%), (E)-β-ocimene (4.5%), sabinene (4.2%), epi-α-muurolol (4.1%); δ-cadinene (0.23.8%). In the subspecies occurring in Poland, this essential oil is characterized by a predominance of sesquiterpenes (41.1-79.3%) over the monoterpenes (5.4-19.7%) (Judzentiene and Budiene, 2014; Judzentiene et al. , 2010). Southern Ural 18 Another study in Southern Ural confirmed that the essential oil of A. campestris L. was composed by α-pinene (41%), β-pinene (29.7%), limonene (6.4%) and sabinene (4.5%) (Khalilov et al. , 2001). Iran From Iran, Kazemi et al. (2009) drew the comparative profile of the terpenic compounds of three parts of A. campestris L.; accordingly, it has been found that the flower and stem contain sub-equal levels of monoterpenes (48.1% and 45.8%, respectively), and sesquiterpenes (7.3% and 18.2%, respectively), while the leaves own 60.1% of monoterpenes and 20.9% of sesquiterpenes; all the different parts however contained spathulenol (15.8-29.2%), α-pinene (23-29.2%), β-pinene (4.5-12.6%), bicyclogermacrene (9.1-12%), (Z)-ß-ocimene (3.2- 6.8%), germacrene D (5.3-6.6%), limonene (3.4-6.3), p-cymene (4.8%) and (E)-ß-ocimene (3.9%). Turkey The Turkish essential oil of A. campestris L. aerial part appeared to have a different chemical composition; the main constituents are: tremetone (15.83%), capillin (10.38%), spathulenol (6.47%), β-pinene (6.31%), methyl-eugenol (5.49%), α-thujone (4.78%) and p-cymene (3.75%) (Baykan Erel et al. , 2012). Serbia The essential oil of A. campestris L. growing in Serbia contained approximately equal quantity of monoterpenes (22.5%) and sesquiterpenes (20.8%). Also, it was poor in volatile fractions and the major components found were spathulenol (9.2%) and βpinene (9.1%) (Chalchat et al., 2003). 19 6. Pharmacology of Artemisia campestris L. 6.1 Antioxidant activity 6.1.1. DPPH (diphenyl picrylhydrazyl) radical scavenging activity From Tunisia, the studies found that the antioxidant effect of methanolic extract of shoots possesses the half maximal inhibitory concentration (IC50) of about 730µg/ml (Tlili et al., 2013); while the methanolic extract of leaves and that of the shoots expressed the respective values 22µg/ml and 6µg/ml, when compared to the standard BHT (Butylated hydroxytoluene) (IC50=72µg/ml). The antioxidant provoked by methanolic extract of shoots seems to be more efficient (El Abed et al. , 2014; Megdiche-Ksouri et al., 2015). The aqueous extract of leaves possessed an IC50 equivalent to 160µg/ml, though, this radical scavenging activity is lesser than that of ascorbic acid (IC50=72µg/ml) (Sebai et al., 2014). Otherwise, the leaf extract showed a weak antioxidant effect (IC50>62µg/ml), if compared to that of ascorbic acid which possess an IC50 ranging from 2 to 3.5µg/ml (Sefi et al. , 2013). Another report found that the aqueous fraction from the aerial part expressed an antioxidant activity, corresponding to the IC50: 27.5µg/ml; this value was two times higher than that of the standard BHT (IC50=11.5µg/ml) (Megdiche-Ksouri et al., 2015). However the IC50 of the ethyl acetate fraction was 10µg/ml, which was comparable to that displayed by BHT (IC50=11.5µg/ml) (Megdiche-Ksouri et al., 2015). In regard to the essential oil of leaves, the IC50 was about 1874µg/ml, comparatively to that of ascorbic acid (IC50=2.5µg/ml), the observed activity is too low (Akrout et al., 2010); the same observation was made with the antioxidant effect of essential oil from the aerial part, that has an IC50=94500µg/ml, which is judged to be very feeble when compared to 20 standards: ascorbic acid (IC50=240µg/ml), quercetin (IC50= 280µg/ml) and BHT (IC50=840µg/ml) (Akrout et al., 2011). From Algeria, the essential oil and the phenolic extracts obtained from the leaves and the fruits of A. campestris L. showed an important scavenging activity against DPPH radical, and the IC50 was found to be equal to 39µg/ml; this activity appear to be more effective referring to the standard BHT (IC50=89µg/ml) (Bakchiche and Gherib, 2014). Also, the ethyl acetate extract of the aerial part showed a radical scavenging activity estimated by an IC50=58µg/ml; yet, this effect is lower by comparison to the standard rutin (Djidel and Khennouf, 2014). Karabegović et al. (2011) tested the antioxidant effect of three methanolic extracts recovered by different extraction techniques from the aerial parts of A. campestris L. collected in Bulgaria; as result, it has been asserted that the extracts have relatively the same scavenging potential toward DPPH radical, with an IC50 ranging from 19.8 to 23 µg/ml. 6.1.2. ABTS+ (2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) free radical scavenging activity The phenolic extract from the aerial part of A. campestris L. occurring in Algeria, has been found to possess an IC50= 25mmol Trolox equivalent/g of extract dry weight, which corresponds to the value 573µg/g of dry matter (2006; Djeridane et al., 2007). Otherwise, the phenolic extract from the leaves and fruits gave an antioxidant effect, that corresponds to the IC50=15µg/ml. BHT, used as standard reference, showed higher antioxidant effect, regarding the IC50=4µg/ml) (Bakchiche and Gherib, 2014). Another study showed that the scavenging potential of this radical by aqueous extract was much lower and antioxidant activity was estimated by an IC50=26000µg/ml (Barkat et al. , 2014). According to other reports, it has been demonstrated that the ABTS scavenging 21 activity was estimated to be equivalent to 1737, 1000 and 77µmol Trolox equivalent/g of extract, successively for the aqueous-ethanolic extract, the infusion and the essential oil. These scavenging activities are considered interesting by comparison to the standard BHT that displayed IC50=6513µmol Trolox equivalent/g of extract (Akrout et al., 2011), while the value 16mg Trolox equivalent/g of extract dry weight corresponded to the radical scavenging power reported for the methanolic extract of the shoots (Tlili et al., 2013). 6.1.3. Other in-vitro antioxidant effects The ability of A. campestris L. extracts of preventing the lipid peroxidation by inhibition of β-carotene bleaching have been tested. Consequently, ethyl acetate extract produced 82% of bleaching inhibition and exceeded that of BHT; similarly, chloroform extract also inhibited 79% of β-carotene bleaching (Djidel and Khennouf, 2014). Furthermore, It has been reported that the aqueous extract, the aqueous-ethanolic extract and the essential oil obtained from the aerial part of A. campestris L., showed differential antioxidant effects on the β-carotene/linoleic acid system, with the most pronounced activity of the aqueous extract (88.7%) which was comparable to that of the standard BHT (89%). However this elevated antioxidant effect of the extract is related to the high concentration used which is 9.6 times higher than that of the essential oil and the hydro-alcoholic extract (Akrout et al., 2011). Moreover, many extracts of A. campestris L. have been tested on many reactive oxygen species; thus, ethyl acetate and chloroform extracts showed a high scavenging activity of hydroxyl radicals with 0.17 and 0.22 mg/ml respectively, even though, this activity is lower than that of the vitamin C (Djidel and Khennouf, 2014). Otherwise, the aqueous extract of the aerial part inhibited 75% of the hydroxyl radical and showed 95% of peroxide anion scavenging 22 activity (Aniya et al., 2000), while the concentration 47.5 mg/ml inhibited 50% of the oxidation produced by the superoxide anion (Saoudi et al. , 2010). The crude extract and the aqueous extract of A.campestris L. aerial part afforded 100% of ferrous ion chelating activity (Djidel and Khennouf, 2014). Additional studies about the ferric reducing antioxidant power of the methanolic extract, the aqueous and the ethyl acetate fractions of the aerial part of the plant exhibited the respective efficient doses: 110, 230 and 340µg/ml, which was far from that of the standard ascorbic acid (IC50=37µg/ml) (Megdiche-Ksouri et al., 2015). Additionally, ethyl acetate and chloroform extracts of the aerial part increased the reducing power, with respective efficient doses: 45 and 170µg/ml, still the electron donation capacity of the extracts remain inferior to that of the standard BHT (Djidel and Khennouf, 2014). The phenolic extracts from the aerial part, at different concentrations have been assayed for their capacity to protect human blood against the free radical aggression. Consequently, the concentration 10-4M of the phenolic extract produced 208% of inhibition of the hemolysis, while the concentration 30µM inhibited only 50% of the hemolysis (Djeridane et al. , 2010; 2007). One more test allowed to measure the total antioxidant activity by mean of measuring the reducing power of phosphomolybdenum blue by methanolic extract of leaves (55mg ascorbic acid equivalent/g of dry weight) (El Abed et al., 2014), which appear to be much weaker once compared to methanolic extract of shoots (IC50=540mg gallic acid equivalent/g dry weight), aqueous fraction (IC50=216mg gallic acid equivalent/g dry weight) and ethyl acetate fraction (IC50=328mg gallic acid equivalent/g dry weight) (Megdiche-Ksouri et al., 2015) 6.2. Antibacterial activity Recently, many studies have been carried out with the aim of highlighting the capacity 23 of many extracts of A. campestris to prevent the growth of bacterial strains. Methanolic extract seems to exert remarkable antibacterial effect on many bacterial strains and with various zone of inhibition. El Abed et al. (2014) and Naili et al. (2010) showed a significant antibacterial effect of the methanol extract of leaves of A. campestris against a wide range of bacteria such as Escherichia coli (17 and 10mm), Bacillus cereus (25mm), Bacillus subtilis (21 to 32mm), Staphylococcus aureus (20 and 27mm), Salmonella enteritidis and Salmonella typhi (13 and 8mm), Pseudomonas aeruginosa (9mm) compared to the effects of chloramphenicol (20 -33mm), streptomycin (1222mm) and ceftazidime (12-27mm). Similarly examined the effect of two types of methanol extracts of the aerial part against seven strains of bacteria; the best action was obtained against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, with the zones of inhibition ranging from 18 to 21mm; these effects appear to be higher than those obtained with erythromycin (20-20.5mm) and tylosin Tartarat (17-18mm). On the contrary, other authors reported little or no antibacterial effect of methanolic extract or compounds isolated from methanolic extract of the aerial part of A.campestris (Baykan Erel et al., 2012; Megdiche-Ksouri et al., 2015; Tharib et al. , 1983) compared to standard antibiotics. Also, the ethyl acetate fraction from the aerial part exhibited significant levels of inhibition against Bacillus thuringiensis (18.3mm), Listeria monocytogene (13.5mm), Escherichia coli (13 mm), Aeromonas hydrophila (12mm), Vibrio parahaemolyticus (9mm), Staphylococcus aureus (9mm), Vibrio alginolyticus (10mm), Vibrio cholerac (11mm) and Vibrio vulnificus (10.5mm) strains, but, this effect is considered weak compared to the examined standards: gentamicine (15-46 mm) and chloramphenicol (8-30 mm) (Megdiche-Ksouri et al., 2015). Moreover, the essential oil displayed varying 24 magnitude of inhibition patterns with Escherichia coli (18-20mm), Pseudomonas aeruginosa (18mm) and Staphylococcus aureus (10.5-14mm), the results seem to be close to those found with the antibiotics tested: ceftazidine and gentamicine (14-22 mm) (Akrout et al., 2010; 2007; Baykan Erel et al., 2012; Ghorab et al. , 2013). However, the acetone and the aqueous extracts possessed relatively weak activity towards the microorganisms: Staphylococcus aureus (7.7-13mm), Vibrio parahaemolyticus (10mm), Staphylococcus epidermidis (10mm), Staphylococcus saprophiticus (10mm), Listeria monocytogene (8.5mm), Escherichia coli (7 mm) and Salmonella typhimirium (7mm), when compared to antibiotics: oxacillin, tetracyclin, chloramphenicol, streptomycin, and gentamicine (Ben Sassi et al., 2007; El Abed et al., 2014). 6.3 Antifungal activity A promising antifungal efficiency for several extracts of A. campestris L. against many fungal species has been evidenced. When tested on the strains Trichophyton tonsurans, Trichophyton rubrum and Microsporum canis, the aqueous extract of A. campestris induced 100% of growth inhibition; the same result was obtained with standards voriconazole, fluconazole, itraconazole and amphotericin B (Webster et al. , 2008). Against Candida glabrata, Candida parapsilosis and Candida albicans, the same extract produced 7 mm as zone of inhibition; again, this effect is quite similar to that of amphotericin B (8.4-10mm) (Megdiche-Ksouri et al., 2015). Moreover, the methanolic extract of stems has been noted to possess differential degrees of antifungal activity revealed by different percentages of inhibition against Fusarium oxysporum (54%), Aspergillus fumigatus (47%), Fusarium verticillioides (39%), Penicillium brevicompactum (31%) and Aspergillus flavus (30%) (Zabka et al. , 2011); also, the methanolic extract of this plant blocked the growth of Aspergillus niger and provoked a 25 zone of inhibition about 32.5-33 mm, which is more important than erythromycin (20.5 mm) and tylosin tartarat (18 mm) (Karabegović et al., 2011). Whereas, the zone of inhibition ranging from 7 to 9 mm has been observed after the treatment of Candida glabrata, Candida parapsilosis and Candida krusei and Candida albicans colonies with the methanol and ethyl acetate extracts from the aerial part (Megdiche-Ksouri et al., 2015); this antifungal effect is close to that exerted by the standard amphotericin B . Quite simply, the antifungal effect of the essential oil has been restricted, only, on the variety Trichophyton longifusus, for which the growth inhibition was 65%; the same antifungal effect has been found with miconazole (70% of growth inhibition) (Akrout et al., 2007). 6.4 Insecticidal activity Nowadays, the search for botanical pesticides creates great interest, due to their minor toxic effects on the environment and humans. In this regard, further research about the insecticidal activity of A. campestris L. has been undertaken. It has been found that the methanolic extract of its stem displayed the highest larvicidal activity, with 100% mortality of Culex quinquefasciatus (mosquito larvae), and the appraised value of the LD50 was approximately 23 parts per million (Pavela, 2009). However, the larval mortality induced by the ethanolic extract was quite mild, and killed only 33.6% of the Culex pipiens L. mosquito larvae (Masotti et al., 2012). However, the lifespan of the insects Spodoptera littoralis and Bruchus obtectus were moderately reduced, in response to the treatment with the essential oil, with an average inhibition of 50% (Akrout et al., 2007). Another research study indicated different larvicidal efficiency, represented mainly by the repellency effect on Tribolium castaneum larvae after 2-24 hours of exposure to both hexane and acetone extracts from the aerial part of the plant 26 (Pascual-Villalobos and Robledo, 1998). 6.5. Anthelmintic activity Helminthiasis represent one of the major constraints that livestock producers meet; Also, it is well known that A. campestris L. is an abundant pastoral species especially in arid regions. In this respect, ethanolic and aqueous extracts of this plant have been tested in-vitro for their anthelmintic activity, by using the sheep parasite Haemonchus contortus. Both extracts, at 2 mg/ml, provoked the total inhibition of egg hatching; moreover, after 24 hours of exposure, 100% worm’s mortality had been achieved in the presence of the ethanolic extract at 2mg/ml, while, the same concentration of the aqueous extract killed 70 % of worms (Akkari et al., 2014). 6.6 Antitumor activity The anti-mutagenicity effects are potentially useful as an antitumoral treatment; the anti-mutagenic potential of the essential oil from aerial part of A. campestris has been assessed on two Salmonella typhimurium strains after induction of mutagenicity caused by the incorporation of the carcinogen benzo-[a]-pyrene. As result, the inhibitory percentages 87.3% and 73.2% have been noted, respectively in the presence of the S.typhimurium TA97 and S. typhimurium TA98 assay systems at a dose of 100 µg of the oil/plate (Aicha et al., 2008). Despite all the studies and advances in cancer research, the plant species are regarded as promising sources of new anticancer agents with low toxicity against non-tumoral cells. Many investigations reported the cytotoxic effect of extracts from A. campestris L. against several types of cancerous cells using the colorimetric MTT assay (3-(4,5methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), for assessing the cell viability. 27 When compared to a negative control growth, essential oil of the aerial part of A. campestris L. at 100 µg/ml exhibited 80% of inhibition of HT-29 human adenocarcinoma cell line, followed by the infusion and the hydro-ethanolic extract which showed respectively 87% and 43% of the control growth of HT-29 cells (Akrout et al., 2011), while the hexanic and chloroform extracts demonstrated a weak anticancer profile against the cervix adenocarcinoma (Hela cells) with the correspondent percentage of inhibition 26% and 28%. The chloroform extract showed a less pronounced antiproliferative affect against A431 cells (skin epidermoid carcinoma) with 19% of inhibition, similarly, the methanolic extract, inhibited only, 15% of the MCF7 breast carcinoma cells (Réthy et al. , 2007). An important dose-response cytotoxic effect has been detected with the doses ranging from 25 to 3200 µg/ml of the ethanolic extract on the Hep-2 (human Caucasian hepatocyte carcinoma) and HepG-2 cells (human Caucasian larynx carcinoma) (Vahdati-Mashhadian et al. , 2009). Nonetheless, the concentration range from 25 to 1000µg/ml of the methanolic extract tested on MCF7 and A549 cancerous cell lines and on A7R5 and 293T normal cell lines expressed a very low cytotoxic effect (Erel et al. , 2011). 6.7. Antihypertensive effect According to the clinical trial conducted on 14 adult smoker and non-smoker volunteers, diastolic pressure and heart rate were decreased after 30 – 45mins in both groups after taking a decoction of A. campestris L. leaves at 20 mg/ml. without affecting the mean blood pressure of the latter non-hypertensive group. The percent of men with pre diagnosed hypertension in the cigarette smoking group decreased from 50 to 33%, after one hour from taking the water boiled extract. Whilst this only demonstrated an immediate response, this result showed the potential of Artemisia 28 extract to offset hypertension. (Ben-Nasr et al. , 2014). 7Toxicology of Artemisia campestris L. Two acute toxicity tests of A. campestris L. aqueous extract of leaves, collected in Tunisia have been evaluated on mice. After 24 hours following the intraperitoneal administration of five different doses (1, 2, 3, 4, 5 g/kg) of the extract, general depression and abdominal constriction have been observed at doses higher than 3 g/kg body weight, and the mean value of the median lethal dose (LD50) has been equivalent to 2.5 g/kg of body weight (Sefi et al 2010). However, after the oral administration of the doses 0.0125, 0.025, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2 g/kg of the aqueous extract neither abnormal behavior nor mortality has been detected during the observation period. Thus, the LD50 value was greater than 3.2 g/kg body weight (Sebai et al. 2014). Moreover, toxicity of A. campestris ssp. campestris essential oils from Lithuania has been determined using the brine shrimp (Artemia sp.) assay. The test showed that lethality (LD50) of brine shrimp larvae was about 15 to 20 µg/ml (Judzentiene et al., 2010). On the other hand, marked signs of intoxications, like the irritation in the digestive tracts and diarrhea besides to a proteinuria and hematuria, have been observed when large amounts of young growth of A. campestris L. have been ingested by dromedaries and goats in Tunisia (El Bahri et al. , 1997). 8 Conclusion and perspectives In this review, we report the results of works carried out on A. campestris L., which provide practical support for further research that can be undertaken in the future. Pharmacological studies listed in this document show almost all ethnomedicinal uses of this herb, including anthelmintic, anticancer, antifungal and antimicrobial and many 29 other applications. Concerning the chemical composition of the different parts of A. campestris L., it can be clearly concluded that this species has a variable phytochemical profile, which can possibly justify its bioactive potential. However, the lack of bioguided isolation strategies is unfortunate since all bioassays so far on A. campestris L. concern only the crude extracts or essential oils. Therefore, it would be interesting to explore the path to isolate and purify the chemical components that may be biologically active. In addition, the mechanism of action, the bioavailability and pharmacokinetics of isolated pure compounds will have the greatest interest in the valuation of the obtained pharmacological effect. Another relevant feature that can also contribute to the development of this plant is its use in clinical practice; to date, there is a huge shortage in this regard; therefore, clinical studies are needed to confirm the relevance of its traditional use. Conflict of interest None declared. Acknowledgements We are grateful to Mr. A. Berrichi, Professor in Faculté des Sciences (Département de Biologie, Université Mohammed Premier, Oujda-Maroc) for his huge efforts in the care and maintenance of the plant A. campestris L. growing in his experimental station within the Faculty. We are also thankful to Mr. A. Berraaouan, PhD student and member of ―Laboratoire de Physiologie, Génétique et Ethnopharmacologie‖ URAC-40, (Département de Biologie, Faculté des Sciences, Université Mohammed Premier, Oujda-Maroc) for the high quality of A. campestris L. photos taken in the experimental station. 30 References Aicha N, Ines S, Mohamed BS, Ines B, Soumaya K, Kamel G, et al. Chemical composition, mutagenic and antimutagenic activities of essential oils from (Tunisian) Artemisia campestris and Artemisia herba-alba. J Essent Oil Res 2008;20:471-477. Akkari H, Rtibi K, B’chir F, Rekik M, Darghouth MA, Gharbi M. 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Country Common name Part used Mode of Traditional uses References preparation Morocco Algeria Allal, chih lakhrissi Leaves, Decoction, Antidiabetic, treatment of eye (Bnouham et al., 2002; El flowers, seeds infusion, diseases, melisma and for Hassani et al., 2013; poultice digestive, respiratory and allergic Fakchich and Elachouri, problems 2014) Taguq, tguft, degoufet, Leaves, stems, Decoction, Treatment of cutaneous and (Benchelah et al., 2004; tadjuq, tedjok, alala, fruits, aerial infusion, gastro-intestinal problems, Boudjelal et al., 2013; hellala, tamemmayt, part powder, analeptic, anthelmintic, Boulanouar et al., 2013; poultice antidiabetic, antihypertensive, Djidel et al., 2009; Ferchichi diuretic, vulnerary, circulation et al., 2006; Gast, 1989; regulator, febrifuge, vermifuge, Hammiche and Maiza, 2006) um nefsa emmenagogue and for postpartum care, analeptic Tunisia Dguft , tgouft Leaves, Decoction aerialpart Antivenom, anti-inflammatory, (Ben Sassi et al., 2007; anti-rheumatic, anthelmintic, anti- Leporatti and Ghedira, 2009; eczema and cutaneous issues, 43 treatment of fever, cough, urinary Tlili et al., 2013) infections and digestive problems; used for fever and cough and as a tonic Libya sc’ahâl, togoft, tegoft, taghert, tâghiat, teghoch Spain escoba de río, Flowers, NS Anthelmintic (De Natale and Pollio, 2012) Flowers Decoction Treatment for baldness (Benítez et al., 2010) NS NS Antiulcer, and febrifuge (Guarino et al., 2008; leaves mojariega, tomillo, granilloPeganoSalsoletea Italy Tammarice Leporatti and Ghedira, 2009) Serbia NS Leaves Antihelminthic, antiseptic, NS (Popović et al., 2012) emmenagogue, tonic, nervine Iran Berenjasf (common NS Anticancer NS name to some 44 (Naghibi et al. , 2014) Artemisia sp.) India Nagdona (common Leaves Antivenom NS name to some (Bahekar et al., 2012; Kapoor and Saraf, 2011) Artemisia sp.) Japan Ryukyuyomogi NS NS Treatment of liver, kidney and (Aniya et al., 2000; Minami diabetes disorders and for et al., 2010) jaundice, Argentina Alcanfor USA and Field wormwood, field Canada sagewort Leaves, stems Leaves, roots Infusion, Treatment for cough, bronchitis, (Kujawska and Hilgert, maceration and contusions. 2014) Poultice, tea, Abortifacient, respiratory, (Shemluck, 1982) infusion cutaneous conditions, digestive problems NS: not 45 specified