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.

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Persian Medicine
Ethnobotanical and traditional uses, phytochemical constituents and
biological activities of Eryngium species 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
*
1
Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran,
Iran. 2
Drug and Food Control Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran,
Iran. 3
Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
4
Pharmaceutical Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
5
Pharmacognosy 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: n_sadati@sina.tums.ac.ir.
Highlights
Eryngium is the largest genus of Apiaceae 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.

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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.

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Background
Eryngium is the largest genus of Apiaceae family. It
contains 274 accepted species that are distributed all
around the world especially in Europe, Africa, America
and Australia [1-3]. Eryngium species are spiny
perennial or biennial herbaceous plants with 30 to 150
cm height with vertical roots, one principal stem main
or several stems and elliptic and ovate-oval-shaped
spiny fruits. The spiny leaves are often long and wide,
may have two or three section; basal leaves have
petiole and the stem leaves without petiole with spiny
flattened pods. The inflorescence is commonly
paniculous or pistil cluster shape. Flowers are most
often bisexual, without peduncule; petals are white or
nearly greenish, rarely blue sky [4]. All parts of these
plants produce a pleasant volatile oil. Beside their uses
as food ingredients, these plants are utilized as herbal
remedies for their renowned medicinal properties [5,
6].
Eryngium species have variety of uses in folklore
and traditional medicine in different nations. In
addition, new research demonstrates that different
plant species from this genus are rich sources of
various phytochemicals. In vivo and in vitro
investigations have reported several pharmacological
and biological activities from Eryngium species [5-7].
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 [4]. Young leaves of these
plants which locally called “Chuchagh” are mainly
collected in large quantities from the wild by native
people and sold in local markets for using in different
local foods as a flavoring cooked vegetable [2, 8].
Eryngium genus is one of the medicinal herbs
mentioned in several Persian medicine references by
the name of “Qaracaane” and as its description;
widespread morphologies are mentioned due to
different species and varieties. In Persian medicine,
numerous therapeutic properties as well as good
nutritional values have been mentioned for Eryngium
and the use of its roots is confirmed beside the aerial
parts [9].
Given that there is no review on Iranian species of
Eryngium, the aim of this study is to pay attention to
various prospects of Iranian species of Eryngium,
including pharmacological activity and phytochemical
constituents as well as ethnopharmacological and
traditional uses of these species in Persian medicine
and various nations in other regions of the world to
provide a scientific document for prospective exploits
of natural drugs from these plants for management of
various disorders.
Method and search strategy
Electronic databases including PubMed, Scopus,
Science Direct (ISI Web of Knowledge) and Embase
library were searched for research on Eryngium. The
search period was from 1966 to October 2018. the
search keywords were as follows: “Eryngium”, “E.
caeruleum”, “E. caucasicum”, “E. billardieri”, “E.
kotschyi”, “E. thyrsoideum”, “E. bungei”, “E.
creticum”, “E. glomeratum”, “E. parviflorum”, “E.
bornumulleri”, “E. pyramidale”, “E. wanaturi” or “E.
noeanum”.
Inclusion criteria were in vitro, in vivo or
phytochemical evaluations as well as traditional and
ethnobotany uses of ten Iranian Eryngium species as
well as papers with available English full texts.
Exclusion criteria were review articles and papers with
non-English full-texts.
Results
A total of 57 papers were enrolled in analyses, in
which there 14 reports of E. caucasicum, 5 of E.
caeruleum, 7 of E. billardieri, 6 of E. kotschyi, 5 of E.
bungei, 1 of E. glomeratum, 21 of E. creticum, 1 of E.
pyramidale. Data from the final included articles were
summarized in Tables 1 and Appendix.
Traditional and ethnobotany uses
In different Persian medicine references, various
therapeutic effects and pharmacological actions of
Eryngium have been mentioned including antidote
(antitoxin), diuretic, emmenagogue, aphrodisiac,
galactagogue, digestive, anti-flatulent, anti-
inflammatory and analgesic properties. Other
applications of this plant in Persian medicine are for
pulmonary disease, halitosis, snakebite and insect bites,
cramps and gripes and early stages of lymphatic
filariasis (elephantiasis) [9, 10].
In various regions of Iran specially the northern
provinces, E. caeruleum leaves are used as flavoring
vegetable in different local foods [8, 11]. In southwest
of Iran, E. billardieri is used orally for treatment of
constipation [12]. It is also reported that E. caeruleum
is used as enforcing generative power, diuretic, lenitive
and appetizer [13]. In southeastern of Turkey, roots
decoction and crushed leaves of E. billardieri have
been used for toothache and wound healing,
respectively. Also young fresh shoots are eaten after
peeling [14]. In Jordan E. creticum roots are used for
scorpion and snakes bite [15].

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Table 1 Essential oil analysis of Eryngium species growing in Iran
Eryngium species Part used Method of extraction/
yield (%)
The main components
Eryngium
caeruleum M.B.
(syn: Eryngium
caucasicum
Trautv.)
Aerial parts-
pre-flowering stage
Hydrodistillation (3 h) Cyclobuta, dicyclooctene, hexadecahydro (47.03%),
n-hexadecanoic acid (11.16%), linoleic (5.41%), limonene
(4.23%), cis-α-bisabolene (2.14%) [23].
Arial parts-during
the flowering stage
Hydrodistillation (3 h)/
0.3
Limonene (60.5%) and δ-3-carene (13.0%) [21]
Aerial parts Hydrodistillation (5 h)/
0.65
Limonene (56.7%), β-sesquiphellandrene (8.9%), α-pinene
(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.
E. kotschyi Boiss.)
Aerial parts (at full
flowering stage)
Hydrodistillation (4 h)/
0.6
α-Muurolene (42.0%), β-gurjunene (17.0%), δ-cadinene
(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)/
0.98
Cumin alcohol (55.3%), terpinolene (14.6%), carvacrol
(8.9%) and limonene (7.5%) [26]
Aerial parts
(flowering stage)
Hydrodistillation (3.5
h)/ 0.18
Borneol (44.4%), isobornyl formate (14.7%), isoborneol
(9.2%), 1,8-cineol (9.1%) and camphor (7.9 %) [25]
Microwave-assisted
hydrodistillation (at 700
W for 50 min)
Yomogi alcohol (14.3%), terpinolene (14.2%), cumin alcohol
(13.6%), borneol (12.4%), Z-β-ocimene (10.6%) and
sabinene (6.2%)
Headspace SPME
GC–MS analysis
Borneol (22.1%), camphor (11.1%), terpinolene (8.1%),
carvacrol (7.5%) and yomogi alcohol (5.2%)
Aerial parts Hydrodistillation (5 h)/
0.63
P-cymen-7-ol (55.3%), terpinolene (14.6%), carvacrol
(8.9%), limonene (7.5%), sabinene (3.9%) [29]
E. creticum Lam. Stems (flowering
stage)
Hydrodistillation (2-3.5
h)/0.18
Bornyl acetate (28.4%), camphor (17.8%), α-pinene (12.1%),
germacrene D (9.4%), borneol (8.6%) and α-thujene (4.2%)
[13]
Aerial parts
(flowering stage)
Direct thermal
desorption method
Hexanal (52.9%), heptanal (13.9%), 3,4-dimethylhex-1-ene
(8.95%), 2-butylfuran (2.79%), α-pinene (2.5%) [46]
E. glomeratum L. Aerial parts
(flowering stage)
Hydrodistillation (4
h)/0.73
Cis-chrysanthenyl acetate (27.3%), 14-hydroxy-a-muurolene
(19.6%), α-bisabolol (12%), germacrene D (4.6%), α-pinene
(4.2%) and β-eudesmol (2.9%) [1]
Roots (flowering
stage)
Hydrodistillation (4
h)/0.11
β-Oplopenone (20%), di epicedrenoxide (15.9%), γ-selinene
(15.6%), germacrene D (5.1%), 9-hydroxyisolongifolene
(4.1%), isolongifolene epoxide (3.4%) and c-eudesmol
(3.4%) [1]

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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.

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In Israel, whole plant decoction of E. creticum has
been used for the treatment of anaemia, infertility
problems, poisonings and liver diseases. Also
decoction of fresh leaves has been used for treatment
of snake bites or applied on wounds directly. Leaves
decoction also is used for diabetes treatment [16,17]. E.
creticum leaves and stalk or aerial parts are used for
hypoglycemic effects, anti-poisonous property and
blood properties in Lebanon [18]. Also it has been
reported that E. creticum aerial parts, roots and seeds
are used traditionally as laxative, diuretic, antidote and
treatment of snakebites, poisoning, liver diseases,
tumors, kidney stone, infections, skin diseases,
infertility and anemia in different countries [19, 20].
Phytochemical composition
Table 1 and Figure 1 show the chemical structure and
phytochemical category of compounds from different
parts of Iranian Eryngium species.
Essential oil. Studies have shown that the yield of the
essential oil extracted from the aerial parts, seeds and
roots of Eryngium spp., collected in different growth
conditions of Iran were 0.05-0.98% (v/w). The
essential oil of this plant was found to be a yellowish
liquid. According to the reports, monoterpenoids and
sesquiterpenoids are the major components of
Eryngium spp. oil. Figure 1 shows the structures of
some major active components in the essential oil of
Eryngium spp.
Alcohols and hydrocarbons. Yomogi alcohol (1), and
some hydrocarbons were reported from the essential
oil of Eryngium species collected in Iran such as:
n-hexadecanoic acid (2), 3-hexyne (3),
4-(1,5-dimethylhex-4-enyl) cyclohex-2-enone (4),
hexanal (5), heptanal (6), and 3,4-dimethylhex-1-ene
(7) [21-24].
Monoterpenes. Several monoterpenes including:
monoterpene hydrocarbons, monoterpene alcohols, and
oxygenated monoterpens have been reported as major
components of essential oils from Eryngium spp. It has
been presented that the essential oil of Iranian
Eryngium spp. contains a high amount of monoterpens
hydrocarbons, such as: limonene (8), terpinolene (12),
δ-3-carene (13), (Z)-β-ocimene (9), α-Pinene (10),
sabinene (11) and α-thujene (14). Borneol (15),
isoborneol (16), endo-isofenchol (17), carvacrol (18),
thymol (19), and cumin alcohol (ρ-Cymen-7-ol) (20)
have been reported as the major monoterpen alcohol
while oxygenated monoterpens such as: 1,8-Cineole
(21), camphor (22), chrysanthenyl acetate (23),
isobornyl formate (24), and bornyl acetate (25) have
been reported [1, 13, 21-30].
Sesquiterpenes. Several major sesquiterpene
hydrocarbons identified in the essential oil from
Iranian Eryngium spp. including: δ-Cadinene (26),
trans-β-farnesene (27), β-sesquiphellandrene (28),
cis-α-bisabolene (29), α-muurolene (30),
14-hydroxy-α-muurolene (31), β-gurjunene (32),
valencene (33), germacrene D (34) and γ-Selinene (35).
Moreover, spathulenol (36), α-bisabolol (37),
β-eudesmol (38), γ-eudesmol (39), and 9-hydroxy
isolongifolene (40), as sesquiterpene alcohols and 4-(1,
5-dimethylhex-4-enyl) cyclohex-2-enone (41),
β-oplopenone (42), Di-epi-cedrenoxide (43),
Isolongifolene epoxide (44) as oxygenated
sesquiterpenes, as well as 5-methyl-2-pyrimidone (45),
6-acetoxy-2, 3-dihydro-1H-pyrrolizin (46), 4
(5)-acetyl-1H-imidazole (47) and 2-butylfuran (48)
have been reported [1, 13, 21-24, 27, 28, 30].
Other phytochemicals. Genus Eryngium is known for
it’s secondary metabolites like triterpenoid saponins,
triterpenoids, flavonoids, coumarins, and steroids [7].
Among Eryngium spp. growing in Iran, Erdem et al.
reported five new oleanane-type saponins from the
roots of Eryngium kotschyi including
3-O-α-l-rhamnopyranosyl-(1→4)-β-d-
glucuronopyranosyl-22-O-β, β-dimethylacryloylA1-
barrigenol, 3-O-α-l-rhamnopyranosyl-(1→4)-β-d-
glucuronopyranosyl-22-O-angeloylA1-barrigenol, 3-O
-β-d-glucopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→
6)]-β-d-glucopyranosyl-21,22,28-O-triacetyl-(3β,21β,2
2α)-olean-12-en-16-one, 3-O-β-d-glucopyranosyl-(1
→2)-glucopyranosyl-22-O-β-d-glucopyranosylstegano
genin, 3-O-β-d-galactopyranosyl-(1→2)-[α-l-
arabinopyranosyl-(1→3)]-β-d-glucuronopyranosyl-22-
O-angeloylA1-barrigenol and 3-O-α-l-
rhamnopyranosyl-(1→4)-β-d-glucuronopyranosylolean
olic acid [31]. In addition, Ur Rehman et al. identified
two flavonol glycosides, kaempferol
3-O-[6-O-E-p-coumaroyl]-β-D-glucopyranoside and
kaempferol 3-O-(2"
,6"
-di-O-E-p-coumaroyl)-β-D
-glucopyranoside from E. caeruleum [32]. Three
sesquiterpenes with an unusual carbon skeleton,
1-n-propyl-perhydronaphthaline, and a methyl ketone
eicos-8, 11-dien-18-ol-2-one were isolated from the
fresh aerial parts of E. creticum collected from Sinai
(Egypt) [33].
Pharmacological effects
All biological and pharmacological activities of Iranian
Eryngium including in vitro and in vivo studies were
summarized in Appendix. Various investigations
demonstrated a broad range of pharmacological and
biological activities from different parts and extracts of
these plants are explained below.
Antioxidant activities. As evident oxidative stress
condition is an important cause in the pathogenesis of
different human diseases. Therefore, discovering
natural antioxidants which have positive biological
potentials can lead to developing of new
multifunctional natural drugs to prevent or treat
various human disorders [11, 34]. Various in vitro
studies confirmed remarkable antioxidant potential of
Iranian Eryngium species. Several in vitro
investigations reported that n_hexane, ethyl acetate,
acetone, aqueous fractions, ethanolic and methanolic

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extracts of E. caeruleum aerial parts, leaves and
inflorescence, had remarkable antioxidant properties
by various methods [35-40]. Yurdakok and Gencay
reported that lyophilized extracts from the aerial parts
and roots of E. kotschyi possessed significant
antioxidant properties in three different methods [41].
In vitro investigation revealed that volatile oil
obtained from the seeds of Eryngium bungei
demonstrated antioxidant activity [27]. Ethanol extract
from aerial parts of E. billardieri showed antioxidant
properties by different methods [42]. Methanolic and
aqueous extract from aerial parts of E. creticum
showed remarkable antioxidant activities through
various in vitro methods [19, 20, 43].
Antimicrobial effects. The antibacterial activity from
leaves and aerial parts of E. caeruleum have been
confirmed by several in vitro investigations. Sadiq et al.
reported that methanolic extract and its different
fractions of E. caeruleum aerial parts demonstrated
remarkable antibacterial and antifungal activities
against six bacterial strains and three fungal strains
[44]. Essential oil obtained from the aerial parts of E.
caeruleum showed high antibacterial activity against
six bacterial strains that are important pathogens in
plants and human [23]. Ethanol extract of leaves of E.
caeruleum and E. bungei demonstrated antibacterial
effect against four strains of bacteria that are oral and
skin pathogens [45].
Aqueous extracts obtained from aerial parts and
roots of E. kotschyi possessed antibacterial properties
[41]. E. creticum essential oil possessed antimicrobial
activity against seven methicillin-resistant
Staphylococcus aureus strains [46]. Also, methanolic
extract from the leaves of E. creticum showed
antimicrobial activity [47]. Another study
demonstrated that petroleum ether and methanolic
extract from the leaves of E. creticum demonstrated
antifungal activity against 4 fungi species, although
petroleum ether extract showed higher activities [48].
Essential oil from aerial parts of E. glomeratum
showed antimicrobial activity against 15 microbial
strains [1]. Volatile oil obtained from the seeds of E.
bungei demonstrated notable antifungal effect
comparing with amphotericin B [27].
Anti-inflammatory, analgesic and antinociceptive
effects. Erdem et al. reported that methanolic extract
from whole plant of E. billardieri demonstrated
anti-inflammatory activity in mice. This study also
evaluated anti-inflammatory effect of various fractions
from the aerial parts and roots of E. billardieri. The
results showed that the precipitated portion of butanol
extract of the roots demonstrated significant
anti-inflammatory activity. This anti-inflamatory effect
of the roots can be related to its saponin contents [49].
Küpeli et al. investigated anti-inflammatory and
antinociceptive activities of eight Eryngium species
including E. kotschyi and E. creticum. The aqueous
and ethanolic extracts from roots and aerial parts of
both Eryngium species presented apparent
antinociceptive and anti-inflammatory activities [50].
It has been demonstrated that various fractions of
methanolic extract from the roots of E. kotschyi,
showed remarkably antinociceptive activity in mice
[51]. Petals essential oil of E. pyramidale demonstrated
significant anti-nociceptive, analgesic and
anti-inflammatory activities in rats [52].
Antidiabetic activity. Rehman and Hashmi reported
two new flavone glycosides obtained from the aerial
parts of E. caeruleum. These two components
demonstrated remarkable antidiabetic activities via in
vitro experimental investigations [32].
It has been reported that n-hexane, ethyl acetate and
methanolic extracts of aerial parts of E. caeruleum
possesses antidiabetic effect. Methanolic extract
showed higher inhibitory effect followed by ethyl
acetate and n-hexane extracts [11].
Aqueous extract from aerial parts and roots of E.
creticum demonstrated notable acute
antihyperglycemic activities in rats [53, 54]. Also
methanolic extract of E. creticum illustrated in vitro
anti-lipase activity. As evident, enhanced levels of fatty
acids and triglycerides had important role in
development of type 2 diabetes and insulin resistance
[55].
Cytotoxic, antimutagenic and anticancer activities.
Aqueous extracts of aerial parts and roots from E.
kotschyi possesses cytotoxic activity. Root parts
showed more toxicity activity than aerial parts [56].
Esmaeili et al. evaluated cytotoxic activity of 26
species grown in south-west of Iran. Among these 26
species, only four species were toxic and two out of
these four species containing E. billardieri have shown
cytotoxic effects on all tested cell lines with lower IC50
values [57].
In an in vitro assessment, methanolic extracts of 35
species from southwest of Iran were examined for
prophage induction ability in Escherichia coli K-12(λ).
E. billardieri aerial parts was one of five species that
demonstrated the potency to interact with DNA and
might have cytotoxic effects [12]. Among 15 tested
plant species, aqueous extract of E. creticum showed
the highest antitumor effect by 84.30% inhibition [58].
In vitro assesments demonstrated that methanolic
extracts from both leaves and stems of E. creticum
exerted cytotoxicity effect [20]. Ethanolic extract from
the inflorescences of E. creticum demonstrated
inhibitory effect on mutagenicity in rats [59].
Phytotoxic activity. Seeds volatile oil of E. bungei
was evaluated for phytotoxic activity on six plants. It
demonstrated noticeable effect on germination of the
seeds and epicotyl and radicle growth of these plants
with IC50 values ranging from 1.32 to 2.1 μg/mL [27].
Anti-scorpion, snake and venoms activities.
Aqueous and ethanolic extracts of fresh and dried
leaves and roots of E. creticum demonstrated inhibition
effects on hemolytic activities of Leiurus

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quinquesteiartus scorpion venoms. The extract of fresh
leaf showed higher inhibition of hemolytic activity of
the scorpion venom compared with the extract of dried
leaf. Both fresh and dried roots extracts illustrated
100% inhibition of the snake and scorpion venoms,
although ethanolic extracts from the leaves and roots
increased hemolysis of RBC (red blood cells) rather
than inhibition activity of venom effects on RBC [60].
Roots aqueous extract of E. creticum showed
antagonistic effect against Leiurus quinquestriatus
scorpion venom. The results showed that the extract
inhibited 40-50% of the maximum tracheal muscles
contraction induced by the venom in both guinea pigs
and rabbits. Also, the extract partially inhibited
contraction of rabbit and guinea pig jejunum before
and after exposure to the venom [61].
Anticonvulsant activity. Different doses of
methanolic and polyphenolic extracts of E.
caucasicum inflorescence showed antiepileptic activity
in mice. Polyphenolic extract showed more protection
effect against seizures [62].
Antihypoxic activity. Various disorders such as heart
diseases, hemorrhage, stroke, etc. can be the cause of
hypoxia followed by deleterious effects and tissue
destruction and possible death. Also, hypoxia can
produce nitric oxide and other free radicals [63].
Various doses of methanolic extract and polyphenol
fraction obtain from E. caeruleum inflorescence
demonstrated significant protective effects against
asphyctic, hemic and circulatory models of hypoxia in
mice. The hypoxia effects of extracts were dose
dependent [64].
Renoprotective effect. Renoprotective activity of
methanol extract from the aerial parts of E. caeruleum
was demonstrated in mice. The results of this study
demonstrated that E. caeruleum extract reduced blood
urea nitrogen serum creatinine, and urea in nephrotoxic
mice blood serum. This reduction was significant at the
dose of 200, 400 mg/kg/day from the extract [65].
Antihemolytic activity. Different fractions of acetone
extract obtained from the leaves of E. caeruleum
showed antihemolytic effects on rat erythrocyte [38].
Contractile effect. Contraction induction of E.
kotschyi aerial parts and roots was illustrated on
isolated ileum and detrussor muscle of rat. The results
showed that aqueous extracts of both the aerial parts
and roots had contractile effects in detrusor and ileum
muscle in different doses and various protocols [66].
Food preservative. Raeisi et al. demonstrated that E.
caeruleum leaves extract had good potential for use as
natural preservatives for the extension of fish products
shelf-life.
Two concentrations of ethanolic extracts (2% and
4%) obtained from the leaves of E. caeruleum were
evaluated for effects on the quality deterioration
indices, sensory and microbiological characteristics
and lipid oxidation in silver carp (Hypophthalmichthys
molitrix) fillets within refrigerated storage at 40
C ± 1.
Both concentrations of the leaf extracts illustrated
significant retardation on oxidative deterioration,
bacterial growth and had positive efficacy on sensory
quality [39].
Percutaneous penetration enhancing effect.
Different concentrations of methanol extract and
essential oil from the aerial parts of E. bungei showed
significant enhancing effect on transport of piroxicam
in rat skin. The results showed that both of the
essential oil and methanol extract in various
concentration enhanced piroxicam absorption. The
highest permeation rate was due to the highest
concentration of the essential oil. It illustrated
9.17-fold increase in permeability coefficient of
piroxicam [29]. Another similar study demonstrated
that essential oil from E.caeruleum aerial parts
enhanced permeation of piroxicam significantly
through rat skin. The plant essential oil in 5 % w/v,
showed 8.56-fold increase in permeability coefficient
of piroxicam [28].
Nutrition values. Atomic absorption spectrometer
analysis showed that the E. caeruleum leaf was a good
source of various elements. The amount of iron was
remarkably higher than other minerals (Fe > Zn >
Mn > Cr > Cu) [36]. Metin et al. analyzed the mineral
content of 26 species of edible plant leaves in eastern
Anatolia. Among them E.billardieri had the highest
content of potassium. This study concluded that most
of these plants had significant quantities of essential
nutrients. Micro and macro mineral contents of E.
billardieri were approximately in the middle of the
rang contents of these 26 plants and also was higher
than mineral content of eight selected cultivated
vegetables [67].
Discussion
More than half of the 57 articles that were selected for
this review, are related to recent years (2013-2018). It
can show ever increasingly attention to medicinal
plants for treatment or prevention of diseases in recent
years. Enormous traditional and ethnobotanical uses of
Eryngium species have been reported in Persian
medicine and other regions that require to be evaluated
by clinical trials in humans and more new research.
Although several of these ethnobotanical and
traditional properties have been confirmed with new in
vivo and in vitro studies such as anti-inflammatory,
analgesic and antinociceptive activities, anti-scorpion,
snake and venoms activities and antidiabetic effects.
Some other reported traditional and ethnobotany
activities could be related to proven compounds and
activities of these plants including: 1. Antidote
activities, treatment of liver diseases and poisonings
that can be related to high antioxidant properties. 2.
Chop and break up calculus property and tissue
sclerosis discutient activity that can be related to
anticancer and cytotoxic effects. 3. Elimination of

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spasmodic pain in the bowels and removing gripes and
cramps, flatus discutient property, beneficial in
pulmonary disease and halitosis that can be related to
antibacterial and antifungal activities. 4. Hormonal and
sexual effects such as aphrodisiac and erectile activity,
emmenogogue and galactogogue and treatment of
infertility problems that can be related to phytosterols
compositions. 5. Treatment of anaemia that can be
related to high nutritional value of these Eryngium
species.
According to presence of triterpen saponins
especially olean-type saponins in Eryngium species, it
can be concluded that several medicinal properties of
this genus can be related to these components. It has
been proven that, olean-type saponins which are
glycosides of oleanolic acid found in food and
medicinal plants have several biological and
pharmacological importance. Recently, it was
confirmed that oleanolic acid had antimicrobial and
hepatoprotective power, anti-inflammatory and
antipruritic activities, spasmolytic effect,
anti-angiogenic property, antiallergic, antiviral,
anti-tumor and cytotoxic effects, antihyperlipidemic,
antioxidant, and anti-diabetic activities. These
compounds also can increase the bioavailability of the
active component of some pharmaceuticals. In addition
to these compounds, the presence of flavonoid
derivatives as well as essential oils in these plants are
involved in their biological effects [68].
Although, up to date only a few studies have been
done on the toxicity of the plants belonging to the
genus Eryngium, which can be cytotoxic especially at
high doses. So it is necessary to carry out more toxicity
studies before clinical trials assessments. Also, there is
no clinical information about these beneficial effects.
Investigation about the molecular mechanisms of
chemicals isolated from these Eryngium species that
are responsible for various pharmacological effects
such as cytotoxicity, anticancer activity, etc., can lead
to prospective drug development.
Therefore, recommend future studies which should
be performed are: finding the exact mechanism of
pharmacological effects of Eryngium species that have
been confirmed with in vitro studies, toxicity
evaluation of the plant belonging to genus Eryngium,
clinical studies of the safety and efficacy of Eryngium
species, discovering safe doses that are most effective
for clinical studies and ascertaining the possible
interactions of the genus Eryngium with foods.
Conclusion
Eryngium genus is one of the medicinal herbs
mentioned in several Persian medicine references
which its roots and aerial parts has various therapeutic
properties as well as good nutritional values. Results
acquired from the present review revealed that
Eryngium species were nutritional plants that were
used worldwide as ethnobotanical remedies to manage
a broad range of diseases and several of the various
traditional and ethnobotany properties of Eryngium
genus had been confirmed with new in vivo and in
vitro studies.
Considering enormous diversity of pharmacological
effects of Iranian Eryngium species as well as their
large variety of phytochemical compounds, it can be
concluded that these plants have immense potential for
prospective preparation of herbal medicinal products
and are good candidates for discovering new drugs in
future. Especially considering notable anticancer and
antioxidant properties of Eryngium species, it can lead
to further investigations for development of new
anticancer drugs.
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