REVIEW doi: 10.12032/TMR20190412114

Persian Medicine

Ethnobotanical and traditional uses, phytochemical constituents and biological activities of growing in Iran

Masoumeh Ghajarieh Sepanlou1, Mehran Mirabzadeh Ardakani1, Mannan Hajimahmoodi1, 2, 3, Sima Sadrai4, Gholam-Reza Amin5, Naficeh Sadeghi 2, Seyedeh Nargess Sadati Lamardi1*

1Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2Drug and Food Control Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 3Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. 4Pharmaceutical Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 5Pharmacognosy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

*Corresponding to: Seyedeh Nargess Sadati Lamardi, Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran. E-mail: [email protected].

Highlights Eryngium is the largest genus of family. Some remarkable biological and pharmacological activities of these species have been demonstrated in present scientific studies, including antimicrobial, cytotoxic and anticancer, anti-inflammatory, analgesic and antinociceptive activities as well as antioxidant, antidiabetic, anti-snake and anti-scorpion venom effects.

Traditionality Eryngium genus is one of the medicinal herbs mentioned in several Persian medicine references by the name of “Qaracaane”. It contains 274 accepted species that are distributed all around the world especially in Europe, Africa, America and Australia. Ten species of Eryngium have been identified in Iran including E. caeruleum M.B. (syn: E. caucasicum Trautv.), E. creticum Lam., E. bungei Boiss., E. billardieri F. Delaroche. (syn: E. kotschyi Boiss.), E. glomeratum Lam. (syn: E. parviflorum Sm.), E. bornumulleri Nab., E. pyramidale Boiss. & Husson., E. noeanum Boiss., E. wanaturi Woron. (syn: E. woronowii Bordz.), and E. thyrsoideum Boiss. These species are distributed in all regions of Iran and especially are abundant in the northern provinces such as Gilan and Mazandaran.

Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 148 REVIEW doi: 10.12032/TMR20190412114

Abstract Objective: Eryngium with the 274 accepted species, is the largest genus of Apiaceae family which are distributed all over the world and have been used in traditional remedies to manage various ailments in different nations. Ten species of Eryngium have been identified in Iran including E. caeruleum M.B. (syn: E. caucasicum Trautv.), E. creticum Lam., E. bungei Boiss., E. billardieri F. Delaroche. (syn: E. kotschyi Boiss.), E. glomeratum Lam. (syn: E. parviflorum Sm.), E. bornumulleri Nab., E. pyramidale Boiss. & Husson., E. noeanum Boiss., E. wanaturi Woron. (syn: E. woronowii Bordz.), and E. thyrsoideum Boiss. The aim of the present research is to review pharmacological activity, and phytochemical constituents as well as ethnobotany and traditional uses of Iranian species of Eryngium. Materials and methods: Electronic databases including PubMed, Scopus, Science Direct (ISI Web of Knowledge) and Embase library were comprehensively searched for research on Eryngium. The search period was from 1966 to October 2018. The related articles were selected according to the inclusion and exclusion criterias in our study. Results: A total of 57 papers were enrolled in analyses. The findings showed that Iranian species of Eryngium, had a noticeable diverse of traditional medicinal uses and also broad range of pharmacological activities as well as various phytochemical compounds. Some remarkable biological and pharmacological activities of these species have been demonstrated in present scientific studies, including antimicrobial, cytotoxic and anticancer, anti-inflammatory, analgesic and antinociceptive activities as well as antioxidant, antidiabetic, anti-snake and anti-scorpion venom effects. Conclusion: Iranian Eryngium species have enormous potential for prospective preparation of herbal medicinal products and are good candidates for discovering new drugs. Keywords: Eryngium, Iranian species, Pharmacological activities, Phytochemical compositions, Traditional and ethnopharmacological uses

Abbreviations: RBC, Red blood cells. Acknowledgments: We thank our colleagues who provided insight and expertise that greatly assisted the research. Competing interests: The authors report no conflicts of interest in this work. Contributors: NS designed and supervised the study, wrote the manuscript and edited the content of manuscript. MGS did the electronic databases search, reviewed and selected related articles, wrote the manuscript and edited the content of manuscript. The rest of the co-authors in our team reviewed and edited the content of manuscript finally. Citation: Masoumeh Ghajarieh Sepanlou, Mehran Mirabzadeh Ardakani, Mannan Hajimahmoodi, et al. Ethnobotanical and traditional uses, phytochemical constituents and biological activities of Eryngium species growing in Iran. Traditional Medicine Research, 2019, 4(3): 148-159. Appendix: Appendix is available at https://www.tmrjournals.com/tmr/EN/10.12032/TMR20190412114. Executive Editor: Cui-Hong Zhu. Submitted: 27 February 2019, Accepted: 8 April 2019, Online: 20 April 2019. Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 149 REVIEW doi: 10.12032/TMR20190412114 and various nations in other regions of the world to Background provide a scientific document for prospective exploits of natural drugs from these for management of Eryngium is the largest genus of Apiaceae family. It various disorders. contains 274 accepted species that are distributed all around the world especially in Europe, Africa, America Method and search strategy and Australia [1-3]. Eryngium species are spiny perennial or biennial herbaceous plants with 30 to 150 Electronic databases including PubMed, Scopus, cm height with vertical roots, one principal stem main Science Direct (ISI Web of Knowledge) and Embase or several stems and elliptic and ovate-oval-shaped library were searched for research on Eryngium. The spiny fruits. The spiny leaves are often long and wide, search period was from 1966 to October 2018. the may have two or three section; basal leaves have search keywords were as follows: “Eryngium”, “E. petiole and the stem leaves without petiole with spiny caeruleum”, “E. caucasicum”, “E. billardieri”, “E. flattened pods. The inflorescence is commonly kotschyi”, “E. thyrsoideum”, “E. bungei”, “E. paniculous or pistil cluster shape. Flowers are most creticum”, “E. glomeratum”, “E. parviflorum”, “E. often bisexual, without peduncule; petals are white or bornumulleri”, “E. pyramidale”, “E. wanaturi” or “E. nearly greenish, rarely blue sky [4]. All parts of these noeanum”. plants produce a pleasant volatile oil. Beside their uses Inclusion criteria were in vitro, in vivo or as food ingredients, these plants are utilized as herbal phytochemical evaluations as well as traditional and remedies for their renowned medicinal properties [5, ethnobotany uses of ten Iranian Eryngium species as 6]. well as papers with available English full texts. Eryngium species have variety of uses in folklore Exclusion criteria were review articles and papers with and traditional medicine in different nations. In non-English full-texts. addition, new research demonstrates that different species from this genus are rich sources of Results various phytochemicals. In vivo and in vitro investigations have reported several pharmacological A total of 57 papers were enrolled in analyses, in and biological activities from Eryngium species [5-7]. which there 14 reports of E. caucasicum, 5 of E. Ten species of Eryngium have been identified in Iran caeruleum, 7 of E. billardieri, 6 of E. kotschyi, 5 of E. including E. caeruleum M.B. (syn: E. caucasicum bungei, 1 of E. glomeratum, 21 of E. creticum, 1 of E. Trautv.), E. creticum Lam., E. bungei Boiss., E. pyramidale. Data from the final included articles were billardieri F. Delaroche., (syn: E. kotschyi Boiss.), E. summarized in Tables 1 and Appendix. glomeratum Lam. (syn: E. parviflorum Sm.), E. bornumulleri Nab., E. pyramidale Boiss. & Husson., E. Traditional and ethnobotany uses noeanum Boiss., E. wanaturi Woron. (syn: E. In different Persian medicine references, various woronowii Bordz.), and E. thyrsoideum Boiss. These therapeutic effects and pharmacological actions of species are distributed in all regions of Iran and Eryngium have been mentioned including antidote especially are abundant in the northern provinces such (antitoxin), diuretic, emmenagogue, aphrodisiac, as Gilan and Mazandaran [4]. Young leaves of these galactagogue, digestive, anti-flatulent, anti- plants which locally called “Chuchagh” are mainly inflammatory and analgesic properties. Other collected in large quantities from the wild by native applications of this plant in Persian medicine are for people and sold in local markets for using in different pulmonary disease, halitosis, snakebite and insect bites, local foods as a flavoring cooked vegetable [2, 8]. cramps and gripes and early stages of lymphatic Eryngium genus is one of the medicinal herbs filariasis (elephantiasis) [9, 10]. mentioned in several Persian medicine references by In various regions of Iran specially the northern the name of “Qaracaane” and as its description; provinces, E. caeruleum leaves are used as flavoring widespread morphologies are mentioned due to vegetable in different local foods [8, 11]. In southwest different species and varieties. In Persian medicine, of Iran, E. billardieri is used orally for treatment of numerous therapeutic properties as well as good constipation [12]. It is also reported that E. caeruleum nutritional values have been mentioned for Eryngium is used as enforcing generative power, diuretic, lenitive and the use of its roots is confirmed beside the aerial and appetizer [13]. In southeastern of Turkey, roots parts [9]. decoction and crushed leaves of E. billardieri have Given that there is no review on Iranian species of been used for toothache and wound healing, Eryngium, the aim of this study is to pay attention to respectively. Also young fresh shoots are eaten after various prospects of Iranian species of Eryngium, peeling [14]. In Jordan E. creticum roots are used for including pharmacological activity and phytochemical scorpion and snakes bite [15]. constituents as well as ethnopharmacological and traditional uses of these species in Persian medicine Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 150 REVIEW doi: 10.12032/TMR20190412114

Table 1 Essential oil analysis of Eryngium species growing in Iran Eryngium species Part used Method of extraction/ The main components yield (%) Eryngium Aerial parts- Hydrodistillation (3 h) Cyclobuta, dicyclooctene, hexadecahydro (47.03%), caeruleum M.B. pre-flowering stage n-hexadecanoic acid (11.16%), linoleic (5.41%), limonene (syn: Eryngium (4.23%), cis-α-bisabolene (2.14%) [23]. caucasicum Arial parts-during Hydrodistillation (3 h)/ Limonene (60.5%) and δ-3-carene (13.0%) [21] Trautv.) the flowering stage 0.3 Aerial parts Hydrodistillation (5 h)/ Limonene (56.7%), β-sesquiphellandrene (8.9%), α-pinene 0.65 (6.5%) and δ-2-carene (5.9%) [28] Leaves and stems Hydrodistillation (4 h) Vegetative stages in May (leaves): Coastal plants, 3-Hexyne (46.1%), β-sesquiphellandrene (20.4%) and limonene (10.7%) Hill slope plants, 5-Methyl-2-pyrimidone (53.4%), limonene (12.8%) and 6-acetoxy-2,3-dihydro-1H-pyrrolizin (12.4%) [24] Vegetative phase in June (Leaves): Coastal plants, 4 (5)-Acetyl-1H-imidazole (63.6%), thymol (13.9%) and β-sesquiphellandrene (10.0%) Hill slope plant, β-Sesquiphellandrene (44.3%), limonene (20.1%) and trans-β-farnesene (14.1%) Generative phase in July (stem): Coastal plants, 5-Methyl-2-pyrimidone (74.9%), 4-(1,5-dimethylhex- 4-enyl) cyclohex-2-enone (15.8%) and β-sesquiphellandrene (2.9%) Hill slope plant, β-Sesquiphellandrene (25.8%), 5-methyl-2-pyrimidone (18.7%) and limonene (11.8%) E.billardieri (syn. Aerial parts (at full Hydrodistillation (4 h)/ α-Muurolene (42.0%), β-gurjunene (17.0%), δ-cadinene E. kotschyi Boiss.) flowering stage) 0.6 (6.2%) and valencene (5.7%) [30] E.bungei Boiss. Seed Hydrodistillation (4 h) Chrysanthenyl acetate (20.0%), spathulenol (17.2%), endo-isofenchol (10.8%) and α-pinene (5.1%) [27] Aerial parts Hydrodistillation (5 h)/ Cumin alcohol (55.3%), terpinolene (14.6%), carvacrol 0.98 (8.9%) and limonene (7.5%) [26] Aerial parts Hydrodistillation (3.5 Borneol (44.4%), isobornyl formate (14.7%), isoborneol (flowering stage) h)/ 0.18 (9.2%), 1,8-cineol (9.1%) and camphor (7.9 %) [25] Microwave-assisted Yomogi alcohol (14.3%), terpinolene (14.2%), cumin alcohol hydrodistillation (at 700 (13.6%), borneol (12.4%), Z-β-ocimene (10.6%) and W for 50 min) sabinene (6.2%) Headspace SPME Borneol (22.1%), camphor (11.1%), terpinolene (8.1%), GC–MS analysis carvacrol (7.5%) and yomogi alcohol (5.2%) Aerial parts Hydrodistillation (5 h)/ P-cymen-7-ol (55.3%), terpinolene (14.6%), carvacrol 0.63 (8.9%), limonene (7.5%), sabinene (3.9%) [29] E. creticum Lam. Stems (flowering Hydrodistillation (2-3.5 Bornyl acetate (28.4%), camphor (17.8%), α-pinene (12.1%), stage) h)/0.18 germacrene D (9.4%), borneol (8.6%) and α-thujene (4.2%) [13] Aerial parts Direct thermal Hexanal (52.9%), heptanal (13.9%), 3,4-dimethylhex-1-ene (flowering stage) desorption method (8.95%), 2-butylfuran (2.79%), α-pinene (2.5%) [46] E. glomeratum L. Aerial parts Hydrodistillation (4 Cis-chrysanthenyl acetate (27.3%), 14-hydroxy-a-muurolene (flowering stage) h)/0.73 (19.6%), α-bisabolol (12%), germacrene D (4.6%), α-pinene (4.2%) and β-eudesmol (2.9%) [1] Roots (flowering Hydrodistillation (4 β-Oplopenone (20%), di epicedrenoxide (15.9%), γ-selinene stage) h)/0.11 (15.6%), germacrene D (5.1%), 9-hydroxyisolongifolene (4.1%), isolongifolene epoxide (3.4%) and c-eudesmol (3.4%) [1]

Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 151 REVIEW doi: 10.12032/TMR20190412114

Figure 1 Chemical structures of essential oil analysis reported from Eryngium species growing in Iran

(1) Yomogi alcohol, (2) N-hexadecanoic acid, (3) 3-Hexyne, (4) 4-(1,5-Dimethylhex-4-enyl) cyclohex-2-enone, (5) Hexanal, (6) Heptanal, (7) 3,4-Dimethylhex-1-ene, (8) Limonene, (9) (Z)-β-ocimene, (10) α-Pinene, (11) Sabinene, (12) Terpinolene, (13) δ-3-Carene, (14) α-Thujene, (15) Borneol, (16) Isoborneol, (17) Endo-isofenchol, (18) Carvacrol, (19) Thymol, (20) Cumin alcohol (ρ-Cymen-7-ol), (21) 1,8-Cineole, (22) Camphor, (23) Chrysanthenyl acetate, (24) Isobornyl formate, (25) Bornyl acetate, (26) δ-Cadinene, (27) Trans-β-farnesene, (28) β-Sesquiphellandrene, (29) Cis-α-bisabolene, (30) α-Muurolene, (31) 14-Hydroxy-α-muurolene, (32) β-Gurjunene, (33) Valencene, (34) Germacrene D, (35) γ-Selinene, (36) Spathulenol, (37) α-Bisabolol, (38) β-Eudesmol, (39) γ-Eudesmol, (40) 9-Hydroxy isolongifolene, (41) 4-(1, 5-Dimethylhex-4-enyl) cyclohex-2-enone, (42) β-Oplopenone, (43) Di-epi-cedrenoxide, (44) Isolongifolene epoxide, (45) 5-Methyl-2-pyrimidone, (46) 6-Acetoxy-2, 3-dihydro-1H-pyrrolizin, (47) 4 (5)-Acetyl-1H-imidazole, (48) 2-Butylfuran.

Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 152 REVIEW doi: 10.12032/TMR20190412114 In Israel, whole plant decoction of E. creticum has valencene (33), germacrene D (34) and γ-Selinene (35). been used for the treatment of anaemia, infertility Moreover, spathulenol (36), α-bisabolol (37), problems, poisonings and liver diseases. Also β-eudesmol (38), γ-eudesmol (39), and 9-hydroxy decoction of fresh leaves has been used for treatment isolongifolene (40), as sesquiterpene alcohols and 4-(1, of snake bites or applied on wounds directly. Leaves 5-dimethylhex-4-enyl) cyclohex-2-enone (41), decoction also is used for diabetes treatment [16,17]. E. β-oplopenone (42), Di-epi-cedrenoxide (43), creticum leaves and stalk or aerial parts are used for Isolongifolene epoxide (44) as oxygenated hypoglycemic effects, anti-poisonous property and sesquiterpenes, as well as 5-methyl-2-pyrimidone (45), blood properties in Lebanon [18]. Also it has been 6-acetoxy-2, 3-dihydro-1H-pyrrolizin (46), 4 reported that E. creticum aerial parts, roots and seeds (5)-acetyl-1H-imidazole (47) and 2-butylfuran (48) are used traditionally as laxative, diuretic, antidote and have been reported [1, 13, 21-24, 27, 28, 30]. treatment of snakebites, poisoning, liver diseases, Other phytochemicals. Genus Eryngium is known for tumors, kidney stone, infections, skin diseases, it’s secondary metabolites like triterpenoid saponins, infertility and anemia in different countries [19, 20]. triterpenoids, flavonoids, coumarins, and steroids [7]. Among Eryngium spp. growing in Iran, Erdem et al. Phytochemical composition reported five new oleanane-type saponins from the Table 1 and Figure 1 show the chemical structure and roots of Eryngium kotschyi including phytochemical category of compounds from different 3-O-α-l-rhamnopyranosyl-(1→4)-β-d- parts of Iranian Eryngium species. glucuronopyranosyl-22-O-β, β-dimethylacryloylA1- Essential oil. Studies have shown that the yield of the barrigenol, 3-O-α-l-rhamnopyranosyl-(1→4)-β-d- essential oil extracted from the aerial parts, seeds and glucuronopyranosyl-22-O-angeloylA1-barrigenol, 3-O roots of Eryngium spp., collected in different growth -β-d-glucopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→ conditions of Iran were 0.05-0.98% (v/w). The 6)]-β-d-glucopyranosyl-21,22,28-O-triacetyl-(3β,21β,2 essential oil of this plant was found to be a yellowish 2α)-olean-12-en-16-one, 3-O-β-d-glucopyranosyl-(1 liquid. According to the reports, monoterpenoids and →2)-glucopyranosyl-22-O-β-d-glucopyranosylstegano sesquiterpenoids are the major components of genin, 3-O-β-d-galactopyranosyl-(1→2)-[α-l- Eryngium spp. oil. Figure 1 shows the structures of arabinopyranosyl-(1→3)]-β-d-glucuronopyranosyl-22- some major active components in the essential oil of O-angeloylA1-barrigenol and 3-O-α-l- Eryngium spp. rhamnopyranosyl-(1→4)-β-d-glucuronopyranosylolean Alcohols and hydrocarbons. Yomogi alcohol (1), and olic acid [31]. In addition, Ur Rehman et al. identified some hydrocarbons were reported from the essential two flavonol glycosides, kaempferol oil of Eryngium species collected in Iran such as: 3-O-[6-O-E-p-coumaroyl]-β-D-glucopyranoside and n-hexadecanoic acid (2), 3-hexyne (3), kaempferol 3-O-(2",6"-di-O-E-p-coumaroyl)-β-D 4-(1,5-dimethylhex-4-enyl) cyclohex-2-enone (4), -glucopyranoside from E. caeruleum [32]. Three hexanal (5), heptanal (6), and 3,4-dimethylhex-1-ene sesquiterpenes with an unusual carbon skeleton, (7) [21-24]. 1-n-propyl-perhydronaphthaline, and a methyl ketone Monoterpenes. Several monoterpenes including: eicos-8, 11-dien-18-ol-2-one were isolated from the monoterpene hydrocarbons, monoterpene alcohols, and fresh aerial parts of E. creticum collected from Sinai oxygenated monoterpens have been reported as major (Egypt) [33]. components of essential oils from Eryngium spp. It has been presented that the essential oil of Iranian Pharmacological effects Eryngium spp. contains a high amount of monoterpens All biological and pharmacological activities of Iranian hydrocarbons, such as: limonene (8), terpinolene (12), Eryngium including in vitro and in vivo studies were δ-3-carene (13), (Z)-β-ocimene (9), α-Pinene (10), summarized in Appendix. Various investigations sabinene (11) and α-thujene (14). Borneol (15), demonstrated a broad range of pharmacological and isoborneol (16), endo-isofenchol (17), carvacrol (18), biological activities from different parts and extracts of thymol (19), and cumin alcohol (ρ-Cymen-7-ol) (20) these plants are explained below. have been reported as the major monoterpen alcohol Antioxidant activities. As evident oxidative stress while oxygenated monoterpens such as: 1,8-Cineole condition is an important cause in the pathogenesis of (21), camphor (22), chrysanthenyl acetate (23), different human diseases. Therefore, discovering isobornyl formate (24), and bornyl acetate (25) have natural antioxidants which have positive biological been reported [1, 13, 21-30]. potentials can lead to developing of new Sesquiterpenes. Several major sesquiterpene multifunctional natural drugs to prevent or treat hydrocarbons identified in the essential oil from various human disorders [11, 34]. Various in vitro Iranian Eryngium spp. including: δ-Cadinene (26), studies confirmed remarkable antioxidant potential of trans-β-farnesene (27), β-sesquiphellandrene (28), Iranian Eryngium species. Several in vitro cis-α-bisabolene (29), α-muurolene (30), investigations reported that n_hexane, ethyl acetate, 14-hydroxy-α-muurolene (31), β-gurjunene (32), acetone, aqueous fractions, ethanolic and methanolic Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 153 REVIEW doi: 10.12032/TMR20190412114 extracts of E. caeruleum aerial parts, leaves and both Eryngium species presented apparent inflorescence, had remarkable antioxidant properties antinociceptive and anti-inflammatory activities [50]. by various methods [35-40]. Yurdakok and Gencay It has been demonstrated that various fractions of reported that lyophilized extracts from the aerial parts methanolic extract from the roots of E. kotschyi, and roots of E. kotschyi possessed significant showed remarkably antinociceptive activity in mice antioxidant properties in three different methods [41]. [51]. Petals essential oil of E. pyramidale demonstrated In vitro investigation revealed that volatile oil significant anti-nociceptive, analgesic and obtained from the seeds of Eryngium bungei anti-inflammatory activities in rats [52]. demonstrated antioxidant activity [27]. Ethanol extract Antidiabetic activity. Rehman and Hashmi reported from aerial parts of E. billardieri showed antioxidant two new flavone glycosides obtained from the aerial properties by different methods [42]. Methanolic and parts of E. caeruleum. These two components aqueous extract from aerial parts of E. creticum demonstrated remarkable antidiabetic activities via in showed remarkable antioxidant activities through vitro experimental investigations [32]. various in vitro methods [19, 20, 43]. It has been reported that n-hexane, ethyl acetate and Antimicrobial effects. The antibacterial activity from methanolic extracts of aerial parts of E. caeruleum leaves and aerial parts of E. caeruleum have been possesses antidiabetic effect. Methanolic extract confirmed by several in vitro investigations. Sadiq et al. showed higher inhibitory effect followed by ethyl reported that methanolic extract and its different acetate and n-hexane extracts [11]. fractions of E. caeruleum aerial parts demonstrated Aqueous extract from aerial parts and roots of E. remarkable antibacterial and antifungal activities creticum demonstrated notable acute against six bacterial strains and three fungal strains antihyperglycemic activities in rats [53, 54]. Also [44]. Essential oil obtained from the aerial parts of E. methanolic extract of E. creticum illustrated in vitro caeruleum showed high antibacterial activity against anti-lipase activity. As evident, enhanced levels of fatty six bacterial strains that are important pathogens in acids and triglycerides had important role in plants and human [23]. Ethanol extract of leaves of E. development of type 2 diabetes and insulin resistance caeruleum and E. bungei demonstrated antibacterial [55]. effect against four strains of bacteria that are oral and Cytotoxic, antimutagenic and anticancer activities. skin pathogens [45]. Aqueous extracts of aerial parts and roots from E. Aqueous extracts obtained from aerial parts and kotschyi possesses cytotoxic activity. Root parts roots of E. kotschyi possessed antibacterial properties showed more toxicity activity than aerial parts [56]. [41]. E. creticum essential oil possessed antimicrobial Esmaeili et al. evaluated cytotoxic activity of 26 activity against seven methicillin-resistant species grown in south-west of Iran. Among these 26 Staphylococcus aureus strains [46]. Also, methanolic species, only four species were toxic and two out of extract from the leaves of E. creticum showed these four species containing E. billardieri have shown antimicrobial activity [47]. Another study cytotoxic effects on all tested cell lines with lower IC50 demonstrated that petroleum ether and methanolic values [57]. extract from the leaves of E. creticum demonstrated In an in vitro assessment, methanolic extracts of 35 antifungal activity against 4 fungi species, although species from southwest of Iran were examined for petroleum ether extract showed higher activities [48]. prophage induction ability in Escherichia coli K-12(λ). Essential oil from aerial parts of E. glomeratum E. billardieri aerial parts was one of five species that showed antimicrobial activity against 15 microbial demonstrated the potency to interact with DNA and strains [1]. Volatile oil obtained from the seeds of E. might have cytotoxic effects [12]. Among 15 tested bungei demonstrated notable antifungal effect plant species, aqueous extract of E. creticum showed comparing with amphotericin B [27]. the highest antitumor effect by 84.30% inhibition [58]. Anti-inflammatory, analgesic and antinociceptive In vitro assesments demonstrated that methanolic effects. Erdem et al. reported that methanolic extract extracts from both leaves and stems of E. creticum from whole plant of E. billardieri demonstrated exerted cytotoxicity effect [20]. Ethanolic extract from anti-inflammatory activity in mice. This study also the inflorescences of E. creticum demonstrated evaluated anti-inflammatory effect of various fractions inhibitory effect on mutagenicity in rats [59]. from the aerial parts and roots of E. billardieri. The Phytotoxic activity. Seeds volatile oil of E. bungei results showed that the precipitated portion of butanol was evaluated for phytotoxic activity on six plants. It extract of the roots demonstrated significant demonstrated noticeable effect on germination of the anti-inflammatory activity. This anti-inflamatory effect seeds and epicotyl and radicle growth of these plants of the roots can be related to its saponin contents [49]. with IC50 values ranging from 1.32 to 2.1 μg/mL [27]. Küpeli et al. investigated anti-inflammatory and Anti-scorpion, snake and venoms activities. antinociceptive activities of eight Eryngium species Aqueous and ethanolic extracts of fresh and dried including E. kotschyi and E. creticum. The aqueous leaves and roots of E. creticum demonstrated inhibition and ethanolic extracts from roots and aerial parts of effects on hemolytic activities of Leiurus Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 154 REVIEW doi: 10.12032/TMR20190412114 quinquesteiartus scorpion venoms. The extract of fresh Both concentrations of the leaf extracts illustrated leaf showed higher inhibition of hemolytic activity of significant retardation on oxidative deterioration, the scorpion venom compared with the extract of dried bacterial growth and had positive efficacy on sensory leaf. Both fresh and dried roots extracts illustrated quality [39]. 100% inhibition of the snake and scorpion venoms, Percutaneous penetration enhancing effect. although ethanolic extracts from the leaves and roots Different concentrations of methanol extract and increased hemolysis of RBC (red blood cells) rather essential oil from the aerial parts of E. bungei showed than inhibition activity of venom effects on RBC [60]. significant enhancing effect on transport of piroxicam Roots aqueous extract of E. creticum showed in rat skin. The results showed that both of the antagonistic effect against Leiurus quinquestriatus essential oil and methanol extract in various scorpion venom. The results showed that the extract concentration enhanced piroxicam absorption. The inhibited 40-50% of the maximum tracheal muscles highest permeation rate was due to the highest contraction induced by the venom in both guinea pigs concentration of the essential oil. It illustrated and rabbits. Also, the extract partially inhibited 9.17-fold increase in permeability coefficient of contraction of rabbit and guinea pig jejunum before piroxicam [29]. Another similar study demonstrated and after exposure to the venom [61]. that essential oil from E.caeruleum aerial parts Anticonvulsant activity. Different doses of enhanced permeation of piroxicam significantly methanolic and polyphenolic extracts of E. through rat skin. The plant essential oil in 5 % w/v, caucasicum inflorescence showed antiepileptic activity showed 8.56-fold increase in permeability coefficient in mice. Polyphenolic extract showed more protection of piroxicam [28]. effect against seizures [62]. Nutrition values. Atomic absorption spectrometer Antihypoxic activity. Various disorders such as heart analysis showed that the E. caeruleum leaf was a good diseases, hemorrhage, stroke, etc. can be the cause of source of various elements. The amount of iron was hypoxia followed by deleterious effects and tissue remarkably higher than other minerals (Fe > Zn > destruction and possible death. Also, hypoxia can Mn > Cr > Cu) [36]. Metin et al. analyzed the mineral produce nitric oxide and other free radicals [63]. content of 26 species of edible plant leaves in eastern Various doses of methanolic extract and polyphenol Anatolia. Among them E.billardieri had the highest fraction obtain from E. caeruleum inflorescence content of potassium. This study concluded that most demonstrated significant protective effects against of these plants had significant quantities of essential asphyctic, hemic and circulatory models of hypoxia in nutrients. Micro and macro mineral contents of E. mice. The hypoxia effects of extracts were dose billardieri were approximately in the middle of the dependent [64]. rang contents of these 26 plants and also was higher Renoprotective effect. Renoprotective activity of than mineral content of eight selected cultivated methanol extract from the aerial parts of E. caeruleum vegetables [67]. was demonstrated in mice. The results of this study demonstrated that E. caeruleum extract reduced blood Discussion urea nitrogen serum creatinine, and urea in nephrotoxic mice blood serum. This reduction was significant at the More than half of the 57 articles that were selected for dose of 200, 400 mg/kg/day from the extract [65]. this review, are related to recent years (2013-2018). It Antihemolytic activity. Different fractions of acetone can show ever increasingly attention to medicinal extract obtained from the leaves of E. caeruleum plants for treatment or prevention of diseases in recent showed antihemolytic effects on rat erythrocyte [38]. years. Enormous traditional and ethnobotanical uses of Contractile effect. Contraction induction of E. Eryngium species have been reported in Persian kotschyi aerial parts and roots was illustrated on medicine and other regions that require to be evaluated isolated ileum and detrussor muscle of rat. The results by clinical trials in humans and more new research. showed that aqueous extracts of both the aerial parts Although several of these ethnobotanical and and roots had contractile effects in detrusor and ileum traditional properties have been confirmed with new in muscle in different doses and various protocols [66]. vivo and in vitro studies such as anti-inflammatory, Food preservative. Raeisi et al. demonstrated that E. analgesic and antinociceptive activities, anti-scorpion, caeruleum leaves extract had good potential for use as snake and venoms activities and antidiabetic effects. natural preservatives for the extension of fish products Some other reported traditional and ethnobotany shelf-life. activities could be related to proven compounds and Two concentrations of ethanolic extracts (2% and activities of these plants including: 1. Antidote 4%) obtained from the leaves of E. caeruleum were activities, treatment of liver diseases and poisonings evaluated for effects on the quality deterioration that can be related to high antioxidant properties. 2. indices, sensory and microbiological characteristics Chop and break up calculus property and tissue and lipid oxidation in silver carp (Hypophthalmichthys sclerosis discutient activity that can be related to molitrix) fillets within refrigerated storage at 40C ± 1. anticancer and cytotoxic effects. 3. Elimination of Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 155 REVIEW doi: 10.12032/TMR20190412114 spasmodic pain in the bowels and removing gripes and used worldwide as ethnobotanical remedies to manage cramps, flatus discutient property, beneficial in a broad range of diseases and several of the various pulmonary disease and halitosis that can be related to traditional and ethnobotany properties of Eryngium antibacterial and antifungal activities. 4. Hormonal and genus had been confirmed with new in vivo and in sexual effects such as aphrodisiac and erectile activity, vitro studies. emmenogogue and galactogogue and treatment of Considering enormous diversity of pharmacological infertility problems that can be related to phytosterols effects of Iranian Eryngium species as well as their compositions. 5. Treatment of anaemia that can be large variety of phytochemical compounds, it can be related to high nutritional value of these Eryngium concluded that these plants have immense potential for species. prospective preparation of herbal medicinal products According to presence of triterpen saponins and are good candidates for discovering new drugs in especially olean-type saponins in Eryngium species, it future. Especially considering notable anticancer and can be concluded that several medicinal properties of antioxidant properties of Eryngium species, it can lead this genus can be related to these components. It has to further investigations for development of new been proven that, olean-type saponins which are anticancer drugs. glycosides of oleanolic acid found in food and medicinal plants have several biological and References pharmacological importance. Recently, it was confirmed that oleanolic acid had antimicrobial and 1. Landoulsi A, Roumy V, Duhal N, et al. Chemical hepatoprotective power, anti-inflammatory and composition and antimicrobial activity of the antipruritic activities, spasmolytic effect, essential oil from aerial parts and roots of anti-angiogenic property, antiallergic, antiviral, Eryngium barrelieri Boiss. and Eryngium anti-tumor and cytotoxic effects, antihyperlipidemic, glomeratum Lam. from Tunisia. Chem Biodivers antioxidant, and anti-diabetic activities. These 2016, 13:1720-1729. compounds also can increase the bioavailability of the 2. Abbaspour Z, Jaimand K, Mozaffari S. active component of some pharmaceuticals. In addition Comparison of essential oils compositions of to these compounds, the presence of flavonoid eryngo (Eryngium caucasicum) in different parts derivatives as well as essential oils in these plants are of plant in two growth conditions. J Med Plants involved in their biological effects [68]. By-Products 2015, 4: 83-98. Although, up to date only a few studies have been 3. . A working list of all plant species. done on the toxicity of the plants belonging to the Eryngium. 2013. Available from: genus Eryngium, which can be cytotoxic especially at http://www.theplantlist.org/. high doses. So it is necessary to carry out more toxicity 4. Mozaffarian V. Flora of Iran. Research Institute studies before clinical trials assessments. Also, there is of Forests and Rangelands, Tehran, Iran. 2007. no clinical information about these beneficial effects. 5. Erdem SA, Nabavi SF, Orhan IE, et al. Blessings Investigation about the molecular mechanisms of in disguise: a review of phytochemical chemicals isolated from these Eryngium species that composition and antimicrobial activity of plants are responsible for various pharmacological effects belonging to the genus Eryngium. Daru 2015, 23: such as cytotoxicity, anticancer activity, etc., can lead 53. to prospective drug development. 6. Paul JH, Seaforth CE, Tikasingh T. Eryngium Therefore, recommend future studies which should foetidum L.: a review. Fitoterapia 2011, 82: be performed are: finding the exact mechanism of 302-308. pharmacological effects of Eryngium species that have 7. Wang P, Su Z, Yuan W, et al. Phytochemical been confirmed with in vitro studies, toxicity constituents and pharmacological activities of evaluation of the plant belonging to genus Eryngium, Eryngium L.(Apiaceae). Pharm Crop 2012, 3: clinical studies of the safety and efficacy of Eryngium 99-120. species, discovering safe doses that are most effective 8. Khoshbakht K, Hammer K, Pistrick K. Eryngium for clinical studies and ascertaining the possible caucasicum Trautv. cultivated as a vegetable in interactions of the genus Eryngium with foods. the Elburz Mountains (Northern Iran). Genet Resour Crop Evol 2007, 54: 445-448. Conclusion 9. AghiliShirazi S. Makhzan-ol-Advieh (Storehouse of Medicaments), Sabz Arang,Tehran University Eryngium genus is one of the medicinal herbs of Medical Sciences, Tehran, Iran. 2009 mentioned in several Persian medicine references (originally was written in 1771), 634-635. which its roots and aerial parts has various therapeutic 10. Ansarishirazi A. Ekhtiarat Badiee The Drug properties as well as good nutritional values. Results Distributing Company of Razi, Tehran, Iran. 1993 acquired from the present review revealed that (originally was written in 1368). Eryngium species were nutritional plants that were 11. Dehghan H, Sarrafi Y, Salehi P. Antioxidant and Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 156 REVIEW doi: 10.12032/TMR20190412114 antidiabetic activities of 11 herbal plants from leaves and stems of Eryngium caucasicum Trautv. Hyrcania region, Iran. J Food Drug Anal 2016, 24: from Iran. J Essent Oil Bearing Plants 2011, 14: 179-188. 693-698. 12. Hamzeloo-Moghadam M, Eslami Tehrani B, 25. Mohammadhosseini M, Mahdavi B, Akhlaghi H. Pirani A, et al. A survey about prophage induction Characterization and chemical composition of the ability in Escherichia coli K-12 (λ) by ethnic volatile oils from aerial parts of Eryngium bungei medicinal plants of Kohgiluyeh va Boyerahmad, Bioss.(Apiaceae) by using traditional Iran. Res J Pharmacogn 2014, 1: 7-10. hydrodistillation, microwave assisted 13. Mohammadhosseini M. Hydrodistilled volatile oil hydrodistillation and head space solid phase from stems of Eryngium creticum Lam. in the microextraction methods prior to GC and GC/MS marginal brackish regions of Semnan province by analyses: A comparative approach. J Essent Oil using gas chromatography combined with mass Bearing Plants 2013, 16: 613-623. spectrometry. Asian J Chem 2013, 25: 390-392. 26. Morteza-Semnani K. Essential oil composition of 14. Bulut G, Biçer M, Tuzlacı E. The folk medicinal Eryngium bungei Boiss. J Essent Oil Res 2005, 17: plants of Yüksekova (Hakkari-Turkey). J Fac 485-486. Pharm Istanbul / İstanbul Ecz Fak Derg 2016, 46: 27. Razavi SM, Vahidipour HR, Ghasemian A, et al. 115-124. Chemical composition and bioactivities of the 15. Al-Quran S. Conservation of medicinal plants in volatile oil of the seeds of Eryngium bungei Boiss. Ajlun/ Jordan. J Med Plants Res 2011, 5: Indian J Nat Prod Resour 2018, 9: 9-15. 5857-5862. 28. Saeedi M, Morteza-Semnani K. Effect of the 16. Said O, Khalil K, Fulder S, et al. essential oil of Eryngium caeruleum on Ethnopharmacological survey of medicinal herbs percutaneous absorption of piroxicam through rat in Israel, the Golan Heights and the West Bank skin. J Essent Oil Bearing Plants 2008, 11: region. J Ethnopharmacol 2002, 83: 251-265. 485-495. 17. Yaniv Z, Dafni A, Friedman J, et al. Plants used 29. Saeedi M, Morteza-Semnani K. Penetration- for the treatment of diabetes in Israel. J enhancing effect of the essential oil and Ethnopharmacol 1987, 19:145-151. methanolic extract of Eryngium bungei on 18. Jeambey Z, Johns T, Talhouk S, et al. Perceived percutaneous absorption of piroxicam through rat health and medicinal properties of six species of skin. J Essent Oil Bearing Plants 2009, 12: wild edible plants in north-east Lebanon. Public 728-741. Health Nutr 2009, 12: 1902-1911. 30. Sefidkon F, Dabiri M, Alamshahi A. Chemical 19. Farhan H, Malli F, Rammal H, et al. composition of the essential oil of Eryngium Phytochemical screening and antioxidant activity billardieri F. Delaroche from Iran. J Essential Oil of Lebanese Eryngium creticum L. Asian Pac J Res 2004, 16: 42-43. Trop Biomed 2012, 2: S1217-S1220. 31. Erdem SA, Mitaine-Offer AC, Miyamoto T, et al. 20. Hawraa RHFHM, Ahmad HAKAD, Bassam B. Triterpene saponins from Eryngium kotschyi. Antioxidant, cytotoxic properties and Phytochemistry 2015, 110: 160-165. phytochemical screening of two Lebanese 32. Rehman AU, Hashmi MA, Tehseen Y, et al. medicinal plants. Int Res J Pharm 2013, 4: Antidiabetic flavonol glycosides from Eryngium 132-136. caeruleum. Rec Nat Prod 2017, 11: 229-234. 21. Assadian F, Masoudi S, Nematollahi F, et al. 33. Ayoub NA, Kubeczka KH, Nawwar M. An unique Volatile constituents of Xanthogalum n-propyl sesquiterpene from Eryngium creticum purpurascens Ave-Lall., Eryngium caeruleum MB L.(Apiaceae). Pharmazie 2003, 58: 674-676. and Pimpinella aurea DC. three umbelliferae 34. Farzaei MH, Bahramsoltani R, Abbasabadi Z, et herbs growing in Iran. J Essent Oil Res 2005, 17: al. A comprehensive review on phytochemical 243-245. and pharmacological aspects of E laeagnus 22. Çelik A, Aydınlık N, Arslan I. Phytochemical angustifolia L. Journal of Pharmacy and constituents and inhibitory activity towards Pharmacology 2015, 67:1467-1480. methicillin‐resistant Staphylococcus aureus 35. Ebrahimzadeh M, Nabavi S, Nabavi S, et al. strains of Eryngium species (Apiaceae). Chem Nitric oxide radical scavenging potential of some Biodivers 2011, 8: 454-459. Elburz medicinal plants. African J Biotechnol 23. Dehghanzadeh N, Ketabchi S, Alizadeh A. 2010, 9: 5212-5217. Essential oil composition and antibacterial 36. Ebrahimzadeh MA, Nabavi SM, Nabavi SF, et al. activity of Eryngium caeruleum grown wild in Mineral elements and antioxidant activity of three Iran. J Essent Oil Bearing Plants 2014, 17: locally edible and medicinal plants in Iran. Asian 486-492. J Chem 2010, 22: 6257-6266. 24. Hashemabadi D, Kaviani B. Chemical 37. Nabavi S, Ebrahimzadeh M, Nabavi S, et al. Free constituents of essential oils extracted from the radical scavenging activity and antioxidant Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 157 REVIEW doi: 10.12032/TMR20190412114 capacity of Eryngium caucasicum Trautv and evaluation of the anti-inflammatory and Froripia subpinnata. Pharmacologyonline 2008, 3: antinociceptive activity of Turkish Eryngium 19-25. species. J Ethnopharmacol 2006, 107: 32-37. 38. Nabavi S, Nabavi S, Alinezhad H, et al. 51. Erdem SA, Arıhan O, Mitaine-Offer AC, et al. Biological activities of flavonoid-rich fraction of Antinociceptive effects of Turkish Endemic Eryngium caucasicum Trautv. Eur Rev Med Eryngium kotschyi Boiss. roots by bioactivity Pharmacol Sci 2012, 16: 81-87. guided fractionation. Rec Nat Products 2016, 10: 39. Raeisi S, Ojagh SM, Sharifi‐Rad M, et al. 168-175. Evaluation of Allium paradoxum (MB) G. Don. 52. Fallahzadeh AR, Zarei M, Mohammadi S. and Eryngium caucasicum trauve. Extracts on the Preliminary phytochemical screening, analgesic shelf‐life and quality of silver carp and anti-inflammatory effect of Eryngium (Hypophthalmichthys molitrix) fillets during pyramidale Boiss. & Husson essential oil in male refrigerated storage. J Food Safety 2017, 37: rat. Entomol Applied Sci Lett 2016, 3: 140-147. e12321. 53. Kasabri V, Afifi FU, Hamdan I. Evaluation of the 40. Riekandeh SM, Mazandarani M, Ebrahimzadeh acute antihyperglycemic effects of four selected M, et al. Antioxidant activities of Eryngium indigenous plants from Jordan used in traditional caucasicum Inflorescence. Eur Rev Med medicine. Pharm Biol 2011, 49: 687-695. Pharmacol Sci 2016, 20: 946-949. 54. Jaghabir M. Hypoglycemic effects of Eryngium 41. Yurdakok B, Gencay YE, Baydan E, et al. creticum. Arch Pharm Res 1991, 14: 295-297. Antibacterial and antioxidant activity of 55. Bustanji Y, Issa A, Moulay A, et al. Hormone Eryngium kotschyi and Eryngium maritimum. J sensitive lipase inhibition by selected medicinal Food Agric Environ 2014, 12: 35-39. plants. J Med Plants Res 2011, 5: 4405-4410. 42. Mavi A, Lawrence GD, Kordali Ş, et al. 56. Yurdakök B, Baydan E. Cytotoxic effects of Inhibition of iron‐fructose‐phosphate‐induced Eryngium kotschyi and Eryngium maritimum on lipid peroxidation in lecithin liposome and Hep2, HepG2, Vero and U138 MG cell lines. linoleic acid emulsion systems by some edible Pharm Biol 2013, 51: 1579-1585. plants. J Food Biochem 2011, 35: 833-844. 57. Esmaeili S, Irani M, Moazzeni Zehan H, et al. 43. Ljubuncic P, Azaizeh H, Portnaya I, et al. Cytotoxic activity of some ethnic medicinal plants Antioxidant activity and cytotoxicity of eight from southwest of Iran. Res J Pharmacogn 2016, plants used in traditional Arab medicine in Israel. 3: 43-47. J Ethnopharmacol 2005, 99: 43-47. 58. Oran SA. disc bioassay for some Jordanian 44. Sadiq A, Ahmad S, Ali R, et al. Antibacterial and medicinal plants. Pharm Biol 1999, 37: 296-299. antifungal potentials of the solvents extracts from 59. Khader M, Bresgen N, Eckl P. Antimutagenic Eryngium caeruleum, Notholirion thomsonianum effects of ethanolic extracts from selected and Allium consanguineum. BMC Complement Palestinian medicinal plants. J Ethnopharmacol Altern Med 2016, 16: 478. 2010, 127: 319-324. 45. Alipour M, Khanmohammadi O. Antibacterial 60. Alkofahi A, Sallal A, Disi A. Effect of Eryngium activity of plant extracts against oral and skin creticum on the haemolytic activities of snake and pathogens. Afr J Microbiol Res 2011, 5: scorpion venoms. Phytother Res 1997, 11: 2909-2911. 540-542. 46. Khalili M, Dehdar T, Hamedi F, et al. 61. Afifi FU, Al-Khalil S, Aqel M, et al. Antagonistic Antihypoxic activities of Eryngium caucasicum. effect of Eryngium creticum extract on scorpion Eur Rev Med Pharmacol Sci 2015, 19: venom in vitro. J Ethnopharmacol 1990, 29: 3282-3285. 43-49. 47. Mansour O, Darwish M, Ismail G, et al. 62. Ebrahimzadeh MA, Chitsaz Z, Shokrzadeh M, et Screening of antibacterial activity in vitro of al. Evaluation of anticonvulsant activities of Eryngium creticum. Res J Pharm Technol 2016, 9: Eryngium caucasicum with maximal electroshock 128-130. and kindling model of seizure in mice. Iran J 48. Abou-Jawdah Y, Sobh H, Salameh A. Psychiatry Behav Sci 2017, 11: e3571. Antimycotic activities of selected plant flora, 63. Kiang JG, Tsen K. Biology of hypoxia. ChinJ growing wild in Lebanon, against Physiol 2006, 49: 223. phytopathogenic fungi. J Agric Food Chem 2002, 64. Khalili M, Dehdar T, Hamedi F, et al. 50: 3208-3213. Antihypoxic activities of Eryngium caucasicum 49. Yesilada E, Tanaka S, Tabata M, et al. The and Urtica dioica. Eur Rev Med Pharmacol Sci antiinflammatory activity of the fractions from 2015, 19: 3282-3285. Eryngium billardieri in mice. Phytother Res 1989, 65. Eslami S, Ebrahimzadeh M, Moghaddam HA, et 3: 38-40. al. Renoprotective effect of Eryngium caucasicum 50. Küpeli E, Kartal M, Aslan S, et al. Comparative in gentamicin-induced nephrotoxic mice. Arch Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 158 REVIEW doi: 10.12032/TMR20190412114 Biol Sci 2011, 63: 157-160. 66. SA E. Contractile effects of Eryngium kotschyi Boiss. on rat isolated ileum and detrussor muscle. Kafkas Üniv Vet Fak Derg 2014, 20: 779-785. 67. Turan M, Kordali S, Zengin H, et al. Macro and micro mineral content of some wild edible leaves consumed in Eastern Anatolia. Acta Agric Scand B Soil Plant Sci 2003, 53: 129-137. 68. Sultana N, Ata A. Oleanolic acid and related derivatives as medicinally important compounds. J Enzyme Inhib Med Chem 2008, 23: 739-756.

Submit a manuscript: https://www.tmrjournals.com/tmr TMR | May 2019 | vol. 4 | no. 3 | 159