Proceedings of the Pakistan Academy of Sciences: Pakistan Academy of Sciences B. Life and Environmental Sciences 54 (4): 265–287 (2017) Copyright © Pakistan Academy of Sciences ISSN: 2518-4261 (print), ISSN 2518-427X (online) Review Article

Pharmacological Promises of Genus Artemisia (Asteraceae): a Review

1* 2 3 4 Adil Hussain , Muhammad Q. Hayat , Sumaira Sahreen , Qurrat ul Ain , 1 and Syed A. I. Bokhari

1Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, 44000 Pakistan 2Department of Plant Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan 3Botanical Sciences Division, Pakistan Museum of Natural History, Islamabad 44000, Pakistan 4Department of Biological Sciences, Karakoram International University, Gilgit 15100, Pakistan

Abstract: A huge amount of scientific literature is available about plant extracts and their compounds having great pharmacological importance. Although, plant-based medicines have been used since antiquity, but knowledge about their effectiveness on human health is still unclear. Artemisia genus belongs to the plant family Asteraceae. This genus comprises of about 500 species, which are well known for their medicinal properties. The aim of this review was to provide an insight about recent published scientific literature concerning pharmacological aspects of genus Artemisia. The compilation of literature has been done by using references from important databases such as Science Direct, Medicinal and Aromatic Plants Abstracts, PubMed, Chemical Abstracts, Kings American Dispensatory, SciFinder, Research gate, Google Scholar and Phytochemical and Ethnobotanical Databases. In this review, special emphases have been given to the reported chemical compounds and biological activities from different Artemisia species. This review emphasis on the plant species from genus Artemisia possessing significant phytochemicals holding a broad range of biological actions like antimicrobial, antimalarial, anti-cancerous, antioxidant and anthelmintic activity. Certain crucial drugs have been unveiled from different species of Artemisia. One important constituent focused by researchers is artemisinin, which retains potential anti-malarial assets and is attained from Artemisia annua. Other groups of phytochemicals like flavonoids, steroids, glycosides, terpenoids, caffeoylquinic acids, acetylenes, coumarins and sterols are also found in this crucial genus. This genus also holds great possibilities for comprehensive scrutiny for other biological activities. The effects of constituents from various species of this genus on other deadly diseases may give better consequences. Keywords: Asteraceae, genus Artemisia, phytochemicals, biological activities, bioactive compounds

species are also found in the southern hemisphere 1. INTRODUCTION of the world [2-3]. Around five hundred species of Asteraceae is one of the largest families of herbs and shrubs fall in this genus [4, 5]. This is angiosperms, which contain 1,600 to 1,700 genera basically a cosmopolitan [6] and is considered as and nearly 24,000 species which are distributed in the diverse and largest genus of the Asteraceae mostly all parts of the world, but not found in family [2, 4, 7]. Different other conducts although Antarctica [1, 2]. Artemisia belongs to the family have accredited to the genus from 350 to 550 Asteraceae which is pharmacologically one of the species [3, 5, 8, 9, 10, 11]. Studies by Oberprieler crucial polymorphic genera. Plants of this genus et al. [2] further stretched out the contemporary are mostly found in the temperate sectors of modifications of subtribe Anthemideae northern hemisphere, but limited numbers of corroborating 522 species to the genus. Since

———————————————— Received, July 2017; Accepted, December 2017 *Corresponding author: Adil Hussain; E-mail: [email protected] 266 Adil Hussain et al ancient times plants sources are utilized for food which are pharmacologically active against and medicinal purposes and it has been estimated neurological ailments [21]. These complexes may that around 70-95% population of the globe trusts also play their part as anti-cancerous, on these plant based remedies for primary care antimutagenic and cardio-protective agents [12]. because they have free radical hunting capacity It has been found that plants have the ability to [22]. Studies by Ferreira and Stade [23] revealed generate a lot of secondary metabolites which that polyphenols are chemo preventive occurs naturally, and may be important in representatives because they pull down the level of pharmacologically. These essential metabolites cholesterol and have preventive cell damage may include essential oils, saponins, flavonoids, property. Due to these astounding findings, cyanogenic glycosides, phenols, tannins, phenolic researchers are looking for the replacement of glycosides, unsaturated lactones, and synthetic antioxidants used in foods/medicinal glucosinolates [13, 14, 15] and are predominantly purposes with new naturally occurring harmless utilized in contradiction of multiple diseases like antioxidants [21]. cancer, malaria, hepatitis, inflammation, and The phytochemical and antioxidant activity of fungal, bacterial, and viral infections. Artemisia is different Artemisia species have been checked and expanding medicinal genus among the variety of confirmed by numerous researchers suggesting world cultures [16, 17, 18]. Ethnobotany, that the species from genus Artemisia are rich in economic botany, medicinal importance and different phytochemical constituents with better phytotherapy of this genus have been reviewed antioxidant activity [24–31]. One of the important [19] and an extensive work on Artemisia unfolded plants paved with highest attention different traditional and medicinal uses of its pharmacologically is Artemisia annua, which has species [17]. been extensively studied and hundreds of secondary metabolites have been discovered and In a lot of investigations, plants and their acknowledged so far [32, 33]. Phytochemical products have been screened for health purposes, analysis of this plant authenticates the presence of because voluminous number of people has been sesquiterpenoid along with sesquiterpene lactones indulged openly or ramblingly in the traditional and between these constituents artemisinin is usage of different products from plant origin. highly focused. This compound has endoperoxide Among the numerous herbs used in modern sesquiterpene lactone that act as a bioactive drug medicine, many species of genus Artemisia are constituent [34]. In a study, Iqbal et al. [29] also included. So in this review, the primary confirmed that the ethanolic extract of A. annua objective is to deliver a brief understanding on leaves possess highest amount of phenolics and different species of the genus Artemisia with flavonoids. extraordinary attention on their phytochemistry and pharmacological potentials. Besides A. annua, another important plant is Artemisia amygdalina having prodigious therapeutic and economic prominence. Its 2. PHYTOCHEMICALS AND ANTIOXIDANT chloroform, ethyl acetate, ethanolic, methanolic, ACTIVITY OF Artemisia SPECIES aqueous and crude extracts encloses flavonoid and A plant encompasses a lot of extracts and alkaloids while tri-terpenoids exists only in the phytochemicals and their utilization could be a ethanolic extract. Tannins are present only in the milestone in developing therapeutic strategies for ethyl acetate extract while saponins are present in the treatment of many diseases. This milestone ethanolic and aqueous extracts which is absent in could be easily achieved if their antimicrobial and methanolic, chloroformic and ethyl acetate extract antioxidant worth is well understood [20]. In vitro respectively [28]. Moreover the petroleum ether studies have shown that, polyphenols with extracts of Artimesia amygdalina contain antioxidant potential are plant based compounds artemisinin, while other compounds like terpenes, Pharmacological Promises of Genus Artemisia 267

alkaloids, phenolics, tannins, cardiac glycosides, Oils from Artemisia absinthium (also called and steroids in tissue cultured and wild Artimesia Wormwood) can be used as a cardiac stimulating amygdalina were also observed [24]. agent that have the tendency to mend circulation Also, with their antimicrobial activity, the of blood and also employed as a stomach remedy methanolic extracts from Artemisia scoparia and [44]. The whole plant is also used against diseases Artemisia spicigera have a vigorous free radical like tuberculosis, diabetes, and antihypertensive rummaging potential [35]. Artemisia nilagirica [45]. Studies substantiated that the leaves of this (Clarke) also contain essential compounds in its plant contain certain type of compounds which are extracts like sesquiterpene lactones, exiguaflavone antimalarial [46], antimicrobial activity [47], (A and B), benzo furan and macckianin [36]. This antidiabetic activity [48] and antifertility [49]. On plant is anti-leishmanial, antimalarial anthelmintic, the other hand, some traditional uses of Artemisia antiseptic, astringent, aromatic, anti-inflammatory, absinthium have also been reported by many appetizer, diuretic, antiasthma, and also used for researchers [30-50]. Its extracts have shielding the treatment of leprosy and skin diseases [37]. influence on hepatic impairment and used as a Additionally, its oil also has an antioxidant activity remedy for gastric pain [50]. Furthermore, the [38]. Extracts of Artemisia nilagirica also encloses antioxidant activity and occurrence of phenolic certain other compounds i.e., steroids, terpenoids, compounds and flavonoids in Artemisia flavonoids, saponins, tannins, proteins and absinthium have also been reported [30]. essential oil. Due to the existence of these Flavonoids are essential because they impede the compounds this plant holds a remarkable sensitivity of pain and shows anti-inflammatory antibacterial activity [31]. In one study it has been properties [51]. These inhibit the enzymes corroborated that the hexane, ethyl acetate, responsible for the synthesis of prostaglandins, methanol and water extracts from leaves and that’s why they are anti-inflammatory. Other flower of this plant contain different studies for the revelation of actions of the pain phytochemicals. Leaves contain saponins, killing activity, hepatoprotective and anti- alkaloids, tannins, flavonoid, coumarins, phenols inflammatory potential of Artemisia annua and with steroids and flower contain alkaloids, Artemisia absinthium were also performed [27]. In coumarins, saponins, terpenoids, tannins, one study, the important compound santonin was flavonoids, and phenols which confirms its high detected in different Artemisia species and its therapeutic potential [26]. quantitation was done with the help of HPLC-UV. The identification and quantification of santonin Another important medicinal plant Artemisia was done in the leaves of A. gmelinni, A terra- parviflora is employed for injuries, cuts and for albae, A. scoparia, A. sublesingiana, A. foetida, skin infections [39]. High blood pressure, diabetes, A. schrenkiana, A. frigida, A. absinthium from and anthelmintic infections are also treated with Kazakhstan and also in the extracts of leaves this plant [40]. These advantages of Artemisia of A. cina [52]. parviflora might be due to the amalgamation of phytochemicals present in it [41]. This could be The methanolic extract of Artemisia vulgaris, easily confirmed by a study where various extracts contain phenolics, flavonoids and sesquiterpenoid of aerial parts of Artemisia parviflora showed the type compounds [53] and possess antimicrobial, presence of flavonoids, triterpenoids, sterols, antitumour, antispasmodic, antiseptic, tannins, alkaloids, and coumarins that makes it a antimalarial, hepatoprotective and antirheumatic best nominee for in vitro antioxidant activity and qualities [54]. phytochemicals extraction [42]. Also, Aerial parts of Artemisia vulgaris contain Ahameethunisa and Hopper [43] reported that the polysaccharides which are employed to treat methanolic extracts of A. parviflora possess numerous diseases and carbohydrates extracted greater amount of phenolic compounds as from this plant exhibit several beneficial compared to other extracts. properties. However the main polysaccharide in 268 Adil Hussain et al

Fig. 1. Plant and synflorescences of Artemisia species (Photographs by Adil Hussain).

the infusion is inulin-type fructan [55]. Another Thujone, 1,8-Cineole and α-Pinene having revelation showed that the oils from Artemisia pharmacological importance [59]. An Iranian feddei contain camphor, borneol, cineole, alpha flora Artemisia khorassanica have been assessed terpineol, chamazulene, alpha thujone, alpha and antimalaric compounds like Chrysanthenone, phellandrene, alpha terpinyl acetate, beta palmitic acid and cis-thujone were confirmed [60]. caryophyllene, and teroinen-4-ol with antibacterial Studies on Artemisia indica Willd revealed that potential [56]. Similarly, oil from different plant this plant is helpful to lessen chronic fever, parts (stem, leaf and flower) of Artemisia hepatobiliary and dyspepsia like illnesses [61]. chamaemelifolia Vill. contains compounds like The stem and leaves are anthelmintic, antiseptic, Menthyl acetate, (Z)-nerolidol, 1,8-cineole, antispasmodic, expectorant and stomachic [62]. yomogi alcohol, and artimesyl acetate while the Methanol, ethanol and hydro-methanol extracts aerial parts of Artemisia turcomanica have from the aerial parts of this plant are rich in compounds like spathulenol, camphor, santolina flavonoids, sterols carbohydrates, tri-terpenoids, alcohol and trans beta terpineol [57] and oil of reducing sugars, glycosides and phenolics. The Artemisia spicigera have many chemical ethanolic extracts do not contain Saponins and ingredients like camphor, 1,8-cineole, camphene, tannins, while methanol and hydro-methanol p-cymene with alpha and beta thujone showing extracts contained Saponins and tannins. Also, antibacterial activity [58]. with these compounds, methanolic extracts of A. In another investigation, the essential oil of indica contain amino acids and alkaloids [25]. Artemisia aucheri was assessed in-vitro and In one investigation, phenolic compounds identified compounds includes Linalool, Camphor, have been detected in Artemisia judaica L. where Borneol, р-Cymene, Davanone, α-Thujone, β- the crude ethanol extract of this plant was tested Pharmacological Promises of Genus Artemisia 269 on the black bean aphid Aphis fabae. The transmission can be initiated through transfusion insecticidal activity of the tested crude extract was or inoculation of infected blood from person to due to the phenolic compounds present in it, which person. It could also be transferred through the makes this plant known for the bio-insecticidal placenta of an infected mother to her unborn child activity [63]. Different representative species of [130]. Now a day, five species of Plasmodium the genus Artemisia reported globally are primarily, Plasmodium falciparum, Plasmodium illustrated in figure 1. ovale, Plasmodium malariae, Plasmodium knowlesi and Plasmodium vivax are active in causing human malaria. The life cycle of malaria 3. ANTIMALARIAL ACTIVITY OF Artemisia SPECIES begins when blood is searched as meal by a female Anopheline mosquito (Plasmodium infected) and Malaria is a severe and highly contagious infection inserts sporozoites into the dermal cells [131, faced by human being [127] and a universal health 132]. problem leading to death about 1 million per The parasite is resistant to conventional annum [128]. Malaria in terms of sickness and antimalarial drug that’s why; there is a dire need to death is the world’s most dangerous parasitic develop multiple approaches that can control disease [129] and Plasmodium sp. protozoa are distribution of this disease [34, 129]. Recently responsible for malaria, where the Plasmodium multi-drug resistant strains of the Plasmodium falciparum is prominent in causing infection. The have developed and there are also evidences of the

Fig. 2. Structure of some bioactive compounds derived from different Artemisia species (Source: Wikipedia commons).

270 Adil Hussain et al occurrence of parasites resistant to artemisinin Artemisia nilagirica (Clarke) have reasonably [133]. Several species of Artemisia are employed high potency against plasmodium falciparum in China as antimalarial since prehistoric times [147]. An In vitro examination of crude extracts of especially Artemisia annua, Artemisia apiacea Artemisia abrotanum L. showed that two Hance and Artemisia lancea Vaniot [16, 134]. In compounds (isofraxadin and a novel sequiterpene 1970s, Chinese scientists found the effective 1(S*)-hydroxy-a-bisabloloxide A acetate) are antimalarial medicine, i.e. artemisinin from effective against plasmodium falciparum [148]. Artemisia annua L. which is a Chinese traditional In a rodent antimalarial model, Artemisia medicinal plant [71]. Artemisinin is also obtained vulgaris leaf extract is orally active, nontoxic from different species of Artemisia and other against Plasmodium yoelii and as well as microbial sources through genetic engineering antiparasitic and antidisease weed. This plant has techniques. Malaria and other diseases are treated the tendency to be a low cost antimalarial source with Artemisinin, which is actually a current drug [149]. In other study, the light petroleum and of choice against plasmodium falciparum. ethanol extracts of Artemisia maritima, Artemisia Artemisinin is essentially a sesquiterpenoid, nilegarica and Artemisia japonica, inhibit schizont and it is obtained from the glandular trichomes of maturation and are found to be atimalarial [150]. Artemisia annua [135]. It contains endoperoxide Another investigation revealed fifteen extracts of 3 bridge with in the 1, 2, 3-trioxane system (as Artemisia species from Iran namely; Artemisia shown in figure 2) that holds a significant rank due ciniformis, Artemisia biennis and Artemisia to its antimalarial properties. Artemisia annua, is turanica have better antimalarial activity. wide spread in China and it is utilized since 2000 Dichloromethane extracts of Artemisia ciniformis years to treat malaria [134]. Besides that, the have highest activity followed by Artemisia presence of artemisinin has also been documented biennis and Artemisia turanica [81]. The in Artemisia lancea and Artemisia apiacea [134], dichloroethane extract of Artemisia armeniaca Artemisia cina [136] Artemisia vulgaris, Artemisia Lam. and Artemisia aucheri Boiss. also have japonica [137] and in the upper portions of better antimalarial activity [79]. Artemisia sieberi [138]. Moreover, its presence In the quest of novel antimalarial compounds has also been confirmed in Artemisia absinthium from plants, chloroform extracts fractions of [139], Artemisia dubia and Artemisia indica [140]. Artemisia maciverae against plasmodium berghei Currently, the supreme operational means to have been assessed where triterpenes and alkaloids get rid of the spreading rate of malaria is were found with antimalarial activity [151]. Artemisinin combination therapy (ACT) [141] and Investigations showed that the diverse solvent ACT is recommended by the World Health extracts and volatile oil of Artemisia indica have Organization (WHO) as a principal treatment for Artemisinin and polymethoxy flavanoid having malaria initiated by Plasmodium falciparum [142]. antiprotozoal potential against different protozoal Artemisinin also showed its detrimental effects parasites, showing the antiparasitic worth of against some other parasites together with Artemisia indica. This plant extracts also have a Schistosoma [143], Leishmania [144] and potential malaria prophylactic effect, due to the Toxoplasma [145. ACT is comparatively harmless inhibition of two plasmodial fatty acid medication because it has no clear antagonistic biosynthesis enzymes [152]. reactions or sterling side effects [146]. An In vitro anti leishmanicidal analysis of Studies confirmed that the hydro alcoholic and ethanolic extracts of Artemisia ciniformis, aqueous extracts of Artemisia annua L. are very Artemisia santolina and Artemisia kulbadica operative on malaria and it gives antimalarial showed some compounds which have better anti activity by potentiating artemisinin activity on leishmanicidal activity and found best for Plasmodium [75]. Another study corroborated that leishmaniasis management [153]. In another study, the crude methanolic and ethanolic extracts of the anti-malarial effect have been found In vivo in Pharmacological Promises of Genus Artemisia 271

Iranian flora Artemisia khorassanica [60] and in [121]. Numerous investigations validate the Artemisia turanica Krasch crude extracts against methanolic and ethanolic extracts of Artemisia Plasmodium berghei [116]. A dose dependent species as better antimicrobial candidates [64, 66, antiplasmodial activity of the methanolic extract 76, 97, 110, 120, 121, 168, 169, 170]. In a study from upper part of Artemisia abyssinica against antimicrobial efficacy of methanolic extracts of chloroquine sensitive Plasmodium berghei has upper section of Artemisia diffusa, Artemisia promising antiplasmodial activity [69]. Moreover, oliveriana, Artemisia scoparia and Artemisia other Artemisia species like Artemisia scoparia turanica against S. aureus, B. subtilis, E. coli, C. Waldst. & Kit. And Artemisia spicigera C. Koch albicans and P. aeruginosa has been documented also possess antimalarial and free radical [169]. Important compounds like flavones could scavenging action and the dichloromethane be obtained from Artemisia giraldii that have extracts of these species have moderate level of extraordinary antibiotic action contrary to several antimalarial action [35]. These studies collectively microorganisms including P. aeruginosa, S. endorse the pharmacological importance of aureus, S. lutea, E. coli, Proteus sp, T. viride and Artemisia plants because of their high potency to A. flavus [91]. combat with malaria. Essential oils of Artemisia aucheri contain 4. ANTIMICROBIAL ACTIVITY OF compounds such as decane, p-cymene borneol, Artemisia SPECIES 1,8-cineole, linalool, lavandulol, triene, bornyl Since past decades, a lot of studies have been acetate, p-mentha-8-ol, chrysanthenyl acetate and performed to reveal the anticancer, anti- caryophyllene oxide. These all essential inflammatory and antimicrobial properties of compounds are recovered from the upper portions different constituents of plants [154–159]. The of Artemisia aucheri and the oils from seeds of exploration of novel antimicrobial compounds this plant have better antimicrobial activity against E.Coli, S. aureus and Listeria monocytogenes with high effectiveness for deadly diseases is [171]. today’s continuous and dire need [160]. Researchers are trying to develop effective drugs Similarly, in the essential oil of Artemisia against microbial diseases by dragging their spicigera compounds like, camphor-a-theojone, B- attention towards traditional medicine [161]. There theojone, 1,8-cineole and p-cymene are active are a lot of scientific revelations on the against various types of bacteria, i.e., Bacillus antimicrobial activity of plants [162] and cereus, Serratia marcescens, E. Coli, Enterobacter numerous antimicrobial components have been aerogenes, Citrobacter amalanoficus, Bacillus identified from plant origin which are aromatic or megaterium, St. saprophyticus and Bacillus might be some saturated carbon-based compounds. megatarium [58]. Oils obtained from the aerial These aromatic compounds are attained by means portion of Artemisia incana L. also contain a lot of of ethanolic or methanolic extraction [163]. compounds where camphor and borneol are Saponins and sterols are important compounds abundant, showing inhibitory efficacy against which can be extracted easily when methanol and twenty six bacteria, fifteen fungi and three yeast species [172]. Oils from Artemisia feddei also ethanol are used as extracting solvents [164]. contain important compounds, which are highly Other compounds like polyphenols [165] alkaloids active against obligate anaerobic bacteria [56]. [166] and terpenoids [167] can also be extracted Artemisia chamaemelifolia, Artemisia using methanol and ethanol as extracting solvent. turcomanica and Artemisia sipicigera also possess On the other hand, dichloromethane is also used antibacterial activity [58]. Invitro assessment of for terpenoids extraction [162]. essential oil of Artemisia aucheri Boiss for Fore mostly, the crude alcohol extraction antimicrobial effect authenticates better results method is employed in initial plant screening for against B. cereus, P. vulgaris, P. aeruginosa, S. antimicrobial activities and secondly, several other cereviciae, C. utilis, P. digitatum and A. niger organic extraction methods are implemented [59]. 272 Adil Hussain et al

Table 1. Biological activities of substances, parts and fractions derived from Artemisia species. Plant Species Bioactive part or fraction Bioactive substance Reference Antifungal [64] Artemisia abrotanum L. Ethanolic extract Antibacterial

Aqueous MeOH extract Antitumor [65]

Essential oil, methanolic and ethanolic Antioxidant [66-30] extract Artemisia absinthium L. Hot alcoholic extract Antimalarial [67] Ethanolic extract Cytoprotective [30] Essential Oil Antifungal [68] Aqueous extract Anthelmintic [214]

Methanolic extract Antiplasmodial, [69] Artemisia abyssinica Water and alcoholic extract Antioxidant [70]

Petroleum ether and ethyl acetate extract Antimalarial [71-72] Anti-algal [73]

Methanol, water extract Antibacterial [74] Artemisia annua L. Aqueous and hydro alcoholic extract Antimalarial [75] Essential oil Antibacterial [76] Ethanolic extract Antiulcerogenic [77] Methanol and water extracts Anticancer [74] Artemisia arborescens Essential oils and methanolic extract Antioxidant [66] Artemisia argyi Methanolic extract Antitumor [78] Artemisia armeniaca Lam Dichloromethane extract Antimalarial [79] Essential oil Antimicrobal [59] Artemisia aucheri Boiss Dichloromethane extract Antimalarial [79] Artemisia barrelieri Eudesmanolides Anti-inflammatory [80] Artemisia biennis Ethyl acetate extract Antimalarial [81] Methanolic extract Antitumor [82] Polyacetylene extract Antiviral [83] Crude extract Antihepatitis [84] Artemisia capillaris Methanolic extract Anticancer [82-85] Methanolic extract Antiobesity [82-86] Methanolic extract Anti-inflammatory [82] Antibacterial Artemisia cina Essential Oil Antioxidant [87] DNA protecting Artemisia ciniformis Dichloromethane extract Antimalarial [81]

Methanolic extract Hepatoprotective [88] Artemisia douglasiano Ethanolic extract Antiulcerogenic [89] Artemisia feddei Essential Oil Antibacterial [56] Ethanol, n-hexane, dichloromethane, Artemisia fukudo Cytotoxic [90] ethylacetate, and butanol

Artemisia giroldu Pamp. Flavones Antimicrobial [91] Artemisia iudoviciana Methanolic extract Antimicrobial [92] Contd..... Pharmacological Promises of Genus Artemisia 273

Table 1 (Contd.....) Chloroform, ethyl acetate and n-hexane Antimicrobial [93] extract Artemisia indica Methanol extract Anti-inflammatory [94] Ethyl acetate extract Antitumor [97] Flavone, cirsimaritin Antispasmodic [95] Artemisia judaico Ethanol extract Insecticidal [63]

Ethanolic extract Cytoprotective Artemisia montana [30] Ethanolic extract Antioxidant

Artemisia myriantha Arglabin Antitumor [96] Ethanolic extract Antibacterial [31] Petroleum ether, n-hexane, dEther, Ethanol Phytochemical analysis [98] Artemisia Nilagirica and water

Antioxidant [38] Essential oil Artemisia pacifica Antimicrobial [99] Artemisia princeps Smoke and water soluble extract Anticancerous [100] Ethanolic extract Antioxidant [42] Artemisia parviflora Methanolic extract Anthelmintic [213] Artemisia rehan Ethanolic extract Antimalarial [101]

Methanolic extract Cytotoxic [102]

Dichloromethane extract Antioxidant [103] Insecticidal Artemisia scoparia Methanol extract

Antioxidant Essential oil and methanolic extract Antibacterial [66] Antimalarial Flavonoids Antitumor [65] Artemisia sieversiana Methanolic extract Anthelmintic [213] Cytostatic Antiobesity Artemisia stolonifera Ethanolic extract Anticancer [104] Anti-inflammatory Artemisia tridentata Nutt. Ethanolic extract Plant growth regulator [105] Artemisia xanthochroa Flavonoids Antitumor [65]

Anti-inflammatory Ethyl acetate, Butanol, Water and Antioxidant Activity [106 Chloroform extract

Antibacterial [107] Essential oils Artemisia herba-alba Asso. Aqueous extract Hypoglycemic [108] Essential oil Antiradical [107] Essential oil and crude extract Hypoglycaemic [109] Methanol extract Anti-Listerial [110] Anticancer [82] Artemisia Japonica Methanol extract Antiobesity Anti-inflammatory Anticancer

Artemisia Montana Methanol extract Antiobesity [82] Anti-inflammatory Artemisia judaica Water and alcoholic extract Anti-Diabetic [111] Contd..... 274 Adil Hussain et al

Table 1 (Contd.....)

Anticancer

Artemisia Sylvatica Methanol extract Antiobesity [82] Anti-inflammatory Anticancer

Artemisia Keiskeana Methanol extract Antiobesity [82] Anti-inflammatory Anticancer

Artemisia Selengensis Methanol extract Antiobesity [82] Anti-inflammatory Artemisia khorassanica Ethanol extract Anti-plasmodial [60] Artemisia kulbadica Methanol extract Anticancer [112] Crude extracts Antimalarial [113] Artemisia sieberi Essential oils Antimalarial [114] Ethanol extract Antidiabetic [115]

Ethyl acetate extract Anticancer [112] Artemisia turanica Crude extract Antimalarial [81] Ethanol extract Antimalarial [116] Artemisia santolina Ethanol extract Anticancer Activity [112] Artemisia diffusa Essential oil Anticancer Activity [112] Ethanol, hexane and water extract Antiradical [107]

Aqueous extract [117] Antioxidant, Antitumor

Antidiabetic [118] Essential oils, Ethyl acetate extract Methanolic extract Antibacterial [119-107]

Artemisia campestris L. Essential oils and methanolic extract Antibacterial [120-121]

Essential oil Antioxidant [120, 66, 121]

Antimutagenic [122] Dichloromethane extract, aqueous extract Water and alcoholic extract Anti-venomous [123-124] Ethanolic extract Antioxidant [70] Artemisia afra Essential Oil Antimalarial [101] Artemisia dracunculus L. Essential Oil Antioxidant [68] Essential oil and methanolic extract Antifungal, Antibacterial [68] Artemisia santonicum Essential Oil Antibacterial [66] Essential Oil Antifungal, Antibacterial [68] Artemisia spicigera Dichloromethane extracts Antimalarial Insecticidal [103] Methanolic extract Antioxidant [103] Artemisia thuscula Ethanolic extract Diuretic [125] Antibacterial Artemisia pallens Ethanolic extract [64] Antifungal Antibacterial Essential oil Antioxidant [87] Artimisia vulgaris L. DNA protecting

Methanolic extract Anti-inflammatory [126]

Pharmacological Promises of Genus Artemisia 275

Against certain type of microorganisms, the containing numerous compounds including methanolic extracts of Artemisia campestris L. are saponins, tannins, steroids, flavonoids, terpenoids, considered to be vigorous [120]. This might be proteins and essential oil with better antibacterial due to the presence of bioactive metabolites of action [97]. countless chemical types, like phenolic Studies of Erel et al. [66] substantiated that the compounds. Shoko et al. [170] confirmed that methanolic extracts and essential oils of Artemisia phenolic compounds are very dynamic substances santonicum and Artemisia scoparia holds fine against microorganisms particularly bacteria. antimicrobial activity where Staphylococcus These compounds are quite active in contradiction aureus was the supreme sensitive bacteria to oils. of few Gram-positive species while the same Also these two plants are active against Candida extracts are weak against some Gram-negative albicans respectively. Some bacterial species, viz., species. Artemisia campestris is not merely an Salmonella enteritidis, Escherichia coli O157, antimicrobial plant but also contains effective Salmonella typhi, Listeria monocytogenes and phenolic antioxidants [121]. The antimicrobial Yersinia enterocolitica were tested against the compounds modes of action in bacteria comprises essential oil and compounds of Artemisia annua membrane damage, membrane potential, changes showing their high sensitivity [76]. In another in pH inside the cell, and the synthesis of ATP study, Javid et al. [93] showed the chloroform, [173, 174]. butanol and ethyl acetate extracts of Artemisia Another study revealed the effective anti-viral indica with better inhibitory activities towards properties of Artemisia Parviflora [41]. The Salmonella typhi. On the other hand, chloroform antibacterial effect of crucial oil and crude extracts and n-Hexane extracts of this plant fully hinder the of Artemisia herba-alba Asoo. against Listeria progression of fungal species like Aspergillus monocytogenes have properties, that can hinder flavus and Fusariun solani. the progression of psychrophils resistant Another study indicated that the methanolic organisms [110]. One more study showed that the extracts of Artemisia ludoviciana are more active aqueous and solvent extracts of Artemisia indica against Vibrio cholera because these extracts were highly active against Gram-positive encompasses compounds which are able to disturb organism where S. aureus, was maximally the cell membranes of Vibrio cholerae cells with inhibited [168]. These inhibitions might be due to pH reduction, cell membrane hyperpolarization, the presence of essential compounds like phenols, and cellular ATP reduction [92]. Besides the steroids, triterpenoids, valavinoids, carotenoids, antibacterial and antifungal activities, compounds tetratriterpenoids azadirachtin and ketones [175]. from the extracts of Artemisia annua have anti- Even though, extracts of few Artemisia species algal activity against Microcystis aeruginosa. This like Artemisia aspera and Artemisia parviflora, might be due to the presence of artemisinin which were not effective or having negligible inhibition escalates the level of reactive oxygen species on human and phytopathogenic bacteria [168]. (ROS) in algae cells [73]. Ethanolic extracts of other species of genus Artemisia like Artemisia abrotanum and Artemisia 5. ANTICANCEROUS ACTIVITY OF pallens are active against Pseudomonas cepacia Artemisia SPECIES and Bacillus stearothermophilus. These plants extracts not only possess antibacterial activity but Medicinal plants possess a lot of natural products also have maximum antifungal activity against with better properties for cancer treatment [176]. Trichosporon beigelii and Saccharomyces Plants have numerous essential products like cerevisiae. This suggests that the ethanolic lignin and flavonoids of polyphenols. These extracts of these two novel plants have both products are evaluated in vitro and in vivo to find antibacterial and antifungal potential [64]. potential biological activities like antitumor Artemisia nilagirica is another important plant activity [177]. Beforehand, a lot of studies have 276 Adil Hussain et al been conducted to unfold the in vitro cytotoxic most active compound artemisinin induces action of various plant extracts for their anticancer apoptosis and it does not induce necrosis against action on different types of human cancer cell human lymphoid leukaemia (Molt-4) cells [180]. lines [178, 179]. Hitosugi et al. [193] reported, in the Like previously reported in other plants, myelogenous leukaemia cell line of human (HL- several studies confirmed Artemisia species as 60), Artemisia capillaries smoke and aqueous better cytotoxic and anti-cancerous candidates [30, extracts are responsible for cellular decease, but 90, 102, 126, 180, 197]. The poisonousness of these extracts are not effective in breast cancer Artemisia species on cancer cells has also shown (MCF-7) and other sort of tumour cells. On the in vitro [181, 182] and in vivo [183] respectively. other hand, macro molecular constituents of These activities might be due to the presence of Artemisia capillaris are liable to encourage one or more essential compounds present in the apoptosis in hepatoma cell lines in human [85]. plant. Among those compounds, Artemisinin, is The water soluble extracts of Artemisia argyi are very active ingredient of many Artemisia species not very much active against human tumour cell mainly Artemisia annua, having better cellular lines and also in breast cancer cell lines, but toxicity against human lymphoid leukaemia cells profoundly active in murine tumour cells [194]. In [180] a study, the induction of apoptosis caused by the Also the artemisinin and its allied compounds smoke and water extracts of Artemisia princeps in have the capacity to thwart cellular growth of human breast cancer MCF-7 cells diminishes cells human colorectal and breast cancer [180, 184]. through the mitochondrial alleyway that seems to Other compounds like terpenoids, cesquiterpen be a milestone for breast cancer treatment [100]. lactones and flavonoids are correspondingly Artemisia argyi and Artemisia Asiatic also important antitumor constituents acquired from contain essential compound called flavones, which Artemisia species [185]. Another offshoot of have the potency to impede certain types of cancer artemisinin, called Artesunate, possess both in by promoting apoptosis including human lung vitro and in vivo anticancer properties [186]. cancer, prostate cancer, myeloid leukaemia, gastric A lot of beneficial compounds have also been cancer and melanoma [78, 195]. Nevertheless, well-known in Artemisia absinthium and other researchers found flavones to be Artemisia vulgaris, which have low molecular unproductive in contradiction of human breast weight. These compounds are flavonoids, cancer cells [196]. Similarly, n-hexane extracts of sesquiterpene, lactones, lignans and monoterpenes Artemisia turanica Krash. possess better cytotoxic, [187, 188, 189]. These are considered to be the antiproliferative and anticancer effects against two main vigorous anticancerous compounds of these leukemic cancer cell lines predominantly HL-60 plants [190, 191, 192]. Another study corroborate and K562 [197]. In another study the infusions from aerial parts of Artemisia dichloromethane, methanol, ethyl acetate, and n- vulgaris and Artemisia absinthium contain hexane extracts from upper parts of different polysaccharides which are used in traditional plant Artemisia species (Artemisia ciniformis, Artemisia made medicine [55]. Studies showed that the diffusa Karasch, and Artemisia vulgaris) have crucial consequence of the vigorous constituents potent antiproliferative properties which could be of Artemisia species is apoptosis; it is a programed a promising chemotherapeutic agent in cancer cell death which is initiated via the cell cycle treatment [198]. arrest [85, 90]. Instigation of caspases, Studies confirmed that the ethanolic extracts mitochondrial membrane depolarization potential of Artemisia montana and Artemisia absinthium or the down governing expression of Bcl-2 gene are rich in essential compounds like, flavonoids might also induce apoptosis of cells [100]. Kim et and phenolic acids. These compounds have better al. [90] validates the utilization of Artemisia antioxidant activity and also have cytoprotective fukudo as a defensive measure against cancer. The influence towards oxidative damage in fibroblast- Pharmacological Promises of Genus Artemisia 277

like cells. This validates Artemisia montana and adult worms [209]. Moreover, in ruminants, the Artemisia absinthium both as better nominees for water, aqueous, sodium bicarbonate, the treatment of skin disorders [30]. dichloromethane, and ethanol extracts obtained Extracts of Artemisia scoparia in human from leaves of Artemisia annua have better muscle cancer cells have devastating effect against anthelmintic action [202]. Perennial plant 88-93% cancer cells that endorse anticancer Artemisia indicia also possess this activity. In a activity of this plant extract [102]. Moreover, the study chloroform, methanol and aqueous extracts apex parts of two novel species of Artemisia i.e., of this plant confirmed anthelminthic property Artemisia vulgaris and Artemisia absinthium have against adult earthworm Pheretima posthuma [62]. anthelmintic, antipyretic, cytostatic, stomachic, Artemisia absinthium extracts are also a promising antibacterial, and antitumor actions [68, 199, 200] way to treat GI nematodes of sheep [210]. An while the In vitro assessment of methanol extracts important member of Artemisia is Artemisia herba of other species like Artemisia Japonica, alba, that can be employed for controlling Artemisia stolonifera, Artemisia montana, heterakid infection because it induces Artemisia selengensis, Artemisia capillaris, anthelminthic consequence by dropping worm Artemisia sylvatica, Artemisia scoparia and burden and egg shedding in the diseased birds Artemisia keiskeana possess better anti- [203] and also the methanolic extracts from leaves inflammatory, anticancer, and antiobesity activity of Artemisia herba-alba possess nematicidal [82]. Studies of Emami et al. [112] corroborated activity [211]. The anthelmintic effects on Artemisia sieberi, Artemisia kulbadica, Artemisia Haemonchus contortus from methanol and crude santolina, Artemisia turanica, and Artemisia aqueous and of Artemisia brevifolia have been diffusa with cytotoxic activity in contradiction of proved and it is confirmed that the whole plant human Caucasian hepatocyte and larynx holds strong anthelmintic activity against carcinoma (HepG-2 and Hep-2) cell lines. nematodes [212]. On the other hand, the essential oil of Artemisia pallens have tendency of strong anthelmintic action against Taenia solium, 6. ANTHELMINTIC ACTIVITY OF Pheritima posthuma and Ascaris lumbricoides Artemisia SPECIES [204]. Chloroform extracts of stem and root of Helminthic problems are exceedingly widespread, Artrmisia siversiana, also hold potency to predominantly in the3rd world countries [201] and eradicate H. nana from infected mice [205]. documented as the cause of much chronic The anthelmintic activity of extracts from ailments. Numerous studies have found Artemisia Artemisia parvflora and Artemisia sieversiana was species with potent anthelmintic activity [62, 202, evaluated in vitro and in vivo on Haemonchus 203, 204, 205]. Artemisia cina is one of the best contortus, which is a parasitic nematode of small candidates with anthelmintic activity which ruminants. Methanolic extract of these plants contains santonin, a sesquiterpenic lactone that tested against three different developmental stages might be the reason of this activity [206, 207]. using different assays were found to be better Other species like Artemisia santonica L, anthelmintic candidates [213]. Artemisia maritima, Artemisia herba-alba, Artemisia absinthium, Artemisia vulgaris, An in vitro study was conducted to find an Artemisia afra and Artemisia ludoviciana are also alternative to anthelmintic praziquantel by most prominent species with the same activity checking the activity of the crude aqueous extract [208]. of Artemisia absinthium against H. nana. The extract from Artemisia absinthium was found to In one study, Extracts from Artemisia vestita increase ultrastructural alterations, worm paralysis and Artemisia maritima are found active against and ultimately death in a dose-dependent manner. Haemonchus contortus in infected sheep’s and Also a significant decrease in the EPG and worm indicated significant activity against larvae and burden has been noticed in mice treated with A. 278 Adil Hussain et al absinthium [214]. Such studies clearly indicate 7. Watson, L.E., P.L. Bates, T.M. Evans, M.M. Artemisia species with their ability to control Unwin, & J.R. Estes. 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