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Journal of Ethnopharmacology 134 (2011) 110

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Journal of Ethnopharmacology
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Review

Traditional uses, phytochemistry and pharmacology of asafoetida


(Ferula assa-foetida oleo-gum-resin)A review
Milad Iranshahy, Mehrdad Iranshahi
Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

a r t i c l e

i n f o

Article history:
Received 1 July 2010
Received in revised form 18 October 2010
Accepted 26 November 2010
Available online 3 December 2010
Keywords:
Apiaceae
Asafoetida
Ferula assa-foetida
Oleo-gum-resin
Sesquiterpene coumarins

a b s t r a c t
The old traditional phytomedicine asafoetida, an oleo-gum-resin obtained from the roots of different
Ferula assa-foetida, is used in different countries for various purposes. Asafoetida is not only used as a
culinary spice but also traditionally used to treat various diseases, including asthma, gastrointestinal disorders, intestinal parasites, etc. This oleo-gum-resin has been known to possess antifungal, anti-diabetic,
anti-inammatory, anti-mutagenic and antiviral activities. A wide range of chemical compounds including sugars, sesquiterpene coumarins and polysuldes have been isolated from this plant. Recent studies
have shown new promising antiviral sesquiterpene coumarins from this old phytomedicine. The present
review summarizes the information concerning the traditional uses, phytochemistry and biological activities of asafoetida.
2010 Elsevier Ireland Ltd. All rights reserved.

Contents
1.
2.
3.

4.
5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Traditional uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Coumarins and sesquiterpene coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
Sulfur-containing compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.
Other compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Bioactive compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Discussion and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Asafoetida is an oleo-gum-resin obtained from the exudates of
the roots of the Iranian endemic medicinal plant, Ferula assa-foetida.
This species (Ferula assa-foetida) is often considered to be the main
source of asafoetida, although other Ferula species, such as Ferula
foetida, Ferula rubricaulis, Ferula rigidula, Ferula alliacea and Ferula
narthex, are also sources of asafoetida (Rajanikanth et al., 1984;

Corresponding author at: Department of Pharmacognosy, Biotechnology


Research Center and School of Pharmacy, Mashhad University of Medical Sciences
(MUMS), P.O. Box 91775-1365, Mashhad, Iran. Tel.: +98 511 8823255/66;
fax: +98 511 8823251.
E-mail address: iranshahim@mums.ac.ir (M. Iranshahi).
0378-8741/$ see front matter 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2010.11.067

1
2
2
2
3
4
4
8
8
8
9

Takeoka, 2001; Evans, 2002). Ferula assa-foetida grows wildly in


the central and southern mountains of Iran. The oleo-gum-resin
asafoetida is called Anghouzeh, Khorakoma and Anguzakoma
in Iran. Other names in some different languages are shown in
Table 1. The plant, which belongs to the Apiaceae family, is an
herbaceous perennial with an unpleasant odor that grows to about
2 m in height. The oleo-gum-resin is often obtained by incision of
the roots or removal of the stems. Hardened exudates (oleo-gumresin) are then collected and packed for export. Asafoetida occurs
in two principle forms, tears and mass. Mass is the most common
form of asafoetida in the market (Tyler et al., 1976; Evans, 2002).
Asafoetida has been used as a spice and a folk phytomedicine
for centuries. Asafoetida has a characteristic sulfurous odor and
a bitter taste. It is used as a avoring spice in a variety of foods,

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

Table 1
Various names of asafoetida in some different languages.
Language

Name

Afghan
Arabic
Chinese
Dutch
English
Finnish
French
German
Hindi
Hungarian
Italian
Nepali
Pakistan
Polish
Russian
Spanish
Swedish
Turkish

Kama, Anguza
Shajarat-ul-Heltit, Angudn
A-wei
Duivelsdrek
Asafetida, Stinking assa, Devils dung
Pirunpaska, Pirunpihka
Ase-ftide
Stinkender assand, Teufelsdreck
Hing, Hingu
Ordoggyoker
Asa fetida
Hing, Hingu
Kama, Anguza
Zapaliczka Cuchnaca, Asafetida
Asafetida
Asaftida
Dyvelstrck
Seytan tersi, Seytan boku, Seytanotu

particularly in India. In addition, Nepali people regularly consume it in their daily diets, and it is believed that asafoetida has
aphrodisiac, sedative and diuretic properties (Eigner and Scholz,
1990; Bandyopadhyay et al., 2006). It is traditionally used for
the treatment of different diseases, such as asthma, epilepsy,
stomachache, atulence, intestinal parasites, weak digestion and
inuenza (Zargari, 1996; Takeoka, 2001; Evans, 2002; Lee et al.,
2009). Recent pharmacological and biological studies have also
shown several activities, such as antioxidant (Dehpour et al., 2009),
antiviral (Lee et al., 2009), antifungal (Singh, 2007; Sitara et al.,
2008; Angelini et al., 2009), cancer chemopreventive (Aruna and
Sivaramakrishnan, 1992; Saleem et al., 2001), anti-diabetic (AbuZaiton, 2010), antispasmodic (Fatehi et al., 2004), hypotensive
(Fatehi et al., 2004), and molluscicidal (Kumar and Singh, 2006)
from this oleo-gum-resin.
Along with these biological surveys, there have been a number of phytochemical investigations of asafoetida (Mahran, 1973;
Pangarova and Zapesochnaya, 1975; Rajanikanth et al., 1984;
Buddrus et al., 1985; Banerji et al., 1988; Kajimoto et al., 1989;
Nassar et al., 1995; Nassar and Mohamed, 1998; Abd El-Razek
et al., 2001; Takeoka, 2001; Duan et al., 2002; Khajeh et al.,
2005; Appendino et al., 2006; Bandyopadhyay et al., 2006; Abd
El-Razek, 2007; Ghosh et al., 2009; Lee et al., 2009; Mirzaei
and Hasanloo, 2009). Asafoetida consists of three main fractions,
including resin (4064%), gum (25%) and essential oil (1017%)
(Takeoka, 2001). The resin fraction contains ferulic acid and its
esters, coumarins, sesquiterpene coumarins and other terpenoids.
The gum includes glucose, galactose, l-arabinose, rhamnose, glucuronic acid, polysaccharides and glycoproteins, and the volatile
fraction contains sulfur-containing compounds, monoterpenes and
other volatile terpenoids. Bioassay-guided fractionation studies of
asafoetida have led to the identication of some interesting bioactive compounds; for example, Lee et al. characterized antiviral
sesquiterpene coumarins from asafoetida that are more potent than
amantadine against inuenza A (Lee et al., 2009).
The present review deals with the traditional uses, phytochemistry, and pharmacological studies of asafoetida. In addition, this
review includes bioactive compounds isolated from asafoetida.
2. Traditional uses
We classied the traditional uses according to similar uses of
asafoetida.
Gastrointestinal disorders: In Ayurveda, asafoetida is introduced
as a valuable remedy for atulence (Kapoor, 2001). Asafoetida

roasted in ghee (a claried butter without any solid milk particles or water) is usually used in gastrointestinal disorders because
unprocessed asafoetida causes irritation and inammation (Gogte,
2000). It is also used for the treatment of stomachache in the eastern region of Shimoga of India (Rajakumar and Shivanna, 2009). In
India, asafoetida is traditionally used as an antibacterial agent, an
antispasmodic, a diuretic and a laxative (Srinivasan, 2005). Water
extract of the dried gum is also taken orally as an antihelminthic
(Eigner and Scholz, 1990; Ross, 2005; Bandyopadhyay et al., 2006).
In Iranian folk medicine, asafoetida is used as an antispasmodic,
antihelminthic, and carminative agent. In addition, it is used as a
mild laxative medicine for the elderly (Zargari, 1996). American
people orally use it as an antihelminthic and it is claimed to be a
powerful antispasmodic (Ross, 2005). In China, asafoetida is used
for infestation with intestinal parasites (Emami et al., 2010). In Fiji,
water extract of the dried gum is also taken orally for the treatment
of upset stomach (Ross, 2005).
Nervous disorders: In Ayurveda, asafoetida is introduced as a
valuable remedy for hysteria and nervous disorders (Kapoor, 2001).
In Afghanistan, hot water extract of the dried gum is also taken
orally for hysteria. Nepali people use it as a sedative and a diuretic
spice (Eigner and Scholz, 1990; Ross, 2005; Bandyopadhyay et al.,
2006). In Iranian folk medicine, asafoetida is used as an anticonvulsant (Zargari, 1996) as well as it is chewed as an antiepileptic in
Morocco (Ross, 2005). American people orally use it as a stimulant
to the brain and nerves (Ross, 2005).
Respiratory problems: Apparently, one of the most important
traditional uses of asafoetida is the treatment of asthma. In India,
asafoetida is traditionally used as a useful symptomatic treatment
for angina pectoris and asthma (Srinivasan, 2005). In Ayurveda,
asafoetida is introduced as a valuable remedy for whooping cough,
pneumonia and bronchitis in children. It is also a pulmonary
stimulant (Kapoor, 2001). In Saudi Arabia, dried asafoetida is
medicinally used for whooping cough, asthma, and bronchitis
(Ross, 2005). In Iranian folk medicine, asafoetida is also used
as a medicine for the treatment of asthma (Zargari, 1996). In
Afghanistan and Fiji, the dried gum is taken for whooping cough
(Ross, 2005). In ancient Rome, it was used as a culinary spice and as
a replacement for Silphion cyrenaicum (Appendino et al., 2006). The
aforementioned plant has been used for tuberculosis and incessant
cough.
Impotence: In Ayurveda and traditional medicines of different
countries such as America and Brazil, it is considered to be an
aphrodisiac (Kapoor, 2001; Ross, 2005).
In spite of various applications of asafoetida in different cultures,
its consumption is forbidden in traditional Korean Buddhism (Kim
et al., 2006). In homeopathy, asafoetida is used for low acid levels in
the stomach, stomach pressure, atulence and loose stools (Emami
et al., 2010).
It seems that the most frequent uses of asafoetida are in
upper respiratory diseases, including the treatment of asthma,
bronchitis and whooping cough (as an expectorant), and gastrointestinal disorders as an antihelminthic, anti-atulence and
antispasmodic.
3. Phytochemistry
3.1. Coumarins and sesquiterpene coumarins
Tsukervanik et al. was the rst group to begin to investigate
plants of the genus Ferula in 1935 (Abd El-Razek et al., 2003). Ferula
is a genus rich in coumarins, particularly sesquiterpene coumarins
(Abd El-Razek et al., 2003). To date, many sesquiterpene coumarins
have been identied from this genus. A large number of different
sesquiterpene coumarins have been reported from asafoetida. The
variation in the structures of reported sesquiterpene coumarins

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

may be due to their different sources. In Fig. 1, the chemical structures of sesquiterpene coumarins that have been reported to date
are depicted.
Sesquiterpene coumarins of Ferula assa-foetida include umbelliprenin (1), 5-hydroxyumbelliprenin (2), 8-hydroxyumbelliprenin
(3), tadshiferin (4), asacoumarin A (5), 8-acetoxy-5-Shydroxyumbelliprenin (6), asacoumarin B (7) (the structure
of this compound was revised later and it was revealed that its
structure is the same as that of galbanic acid), assafoetidin (8),
franesiferol A (9), franesiferol B (10), franesiferol C (11), galbanic
acid (12), conferol (13), gummosin (14), assafoetidinol A (15) and
assafoetidinol B (16) (Nassar et al., 1995; Abd El-Razek et al., 2001,
2003; Appendino et al., 2006, 1993; Lee et al., 2009).
Some other sesquiterpene coumarins reported from Ferula
assa-foetida are ferocaulicin (17), epi-samarcandin (18), episamarcandin acetate (19) and kamolonol (20) (Nassar et al., 1995;
Nassar and Mohamed, 1998; Abd El-Razek et al., 2003).
Other studies on Ferula assa-foetida resin have also led to the
isolation of different sesquiterpene coumarins including foetidine
(21), saradaferin (22), 10-R-acetoxy-11-hydroxyumbelliprenin
(23), 10-R-karatavicinol (24), methyl galbanate (25), lehmferin
(26), feselol (27), ligupersin A (28), epi-conferdione (29), microlobin
(30), polyanthinin (31) and umbelliferone (7-hydroxycoumarin)
(Buddrus et al., 1985; Abd El-Razek et al., 2001; Bandyopadhyay
et al., 2006).

3.2. Sulfur-containing compounds


These compounds play an important role in the odor and taste
of asafoetida. Three major sulfur constituents that have been identied in Ferula assa-foetida include 2-butyl 1-propenyl disulde
(32), 1-(methylthio)propyl 1-propenyl disulde (33) and 2-butyl
3-(methylthio)-2-propenyl disulde (34) (Takeoka, 2001).
Some other sulfur constituents include 2-methyl-2propanethiol (35), 2,3-dimethylthiirane (36), 1-methylthio-(Z)1-propene (37), 1-methylthio-(E)-1-propene (38), dimethyl disulde (39), S-methylpropanethioate (40), 2-(methylthio) butane
(41), 3,4-dimethylthiophene (42), methyl (Z)-1-propenyl disulde
(43), methyl (E)-1-propenyl disulde (44), dimethyl trisulde
(45), 2-butyl methyl disulde (46), dipropyl disulde (47), 2,3,4trimethylthiophene (58), 2-butyl vinyl disulde (49), 2-butyl ethyl
disulde (50), 2-butyl propyl disulde (51), 2-butyl 1-propenyl
disulde (52), methyl 1-(methylthio)propyl disulde (53), di-2butyl disulde (54), methyl 1-(methylthio)ethyl disulde (55),
1-(methylthio)propyl propyl disulde (56), 1-(methylthio)propyl
1-propenyl disulde (57) (Takeoka, 2001) and asadisulde (58)
(Kajimoto et al., 1989). Asafoetida also contains 2-butyl methyl
trisulde (59), di-2-butyl trisulde (60) and di-2-butyl tetrasulde
(61) (Fig. 2) (Rajanikanth et al., 1984).
Foetisulde A (62) and foetisulde C (63) are two other polysulde derivatives of asafoetida (Lee et al., 2009). These compounds

R2

COOH

R3

R1

1 R1= R2 =R3= H

HO

7
O

2 R1= OH, R2=R3= H


3 R1=R3= H, R2= OH

R1

4 R1=R2= H, R3= OH

R2

5 R1=R2= OH, R3 = H

HO

10

9 R1= OH, R2 = H

6 R1= OH, R2= OAc, R3= H

14 R1 = H, R2 = OH

O
O

O
13

HOOC

HO
12

11

R1
H

OH

R3

R4
R1
R2

R3

AcO
O

15 R1= OH, R2=R3= H


16 R1= H, R2= OAc, R3= OH

O
O

R2

17

18 R1= H, R2= OH, R3=Me, R4= OH


19 R1= H, R2= OAc, R3=Me, R4= OH

Fig. 1. Sesquiterpene coumarins isolated from asafoetida.

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

O
O

O
O

H
20

21

HO

OH

HO

22

O
O

HO
23

OH

26

HO

25

24

27

28

HO

O
O

29
O

HO

O
H3COOC

HO
OAc

30

AcO

OH

31

Fig. 1. (Continued )

have also been reported from the roots of Ferula foetida (Duan et
al., 2002).
3.3. Other compounds
The compounds of Ferula assa-foetida are not limited to
sesquiterpene coumarins and sulfur-containing compounds; it also
contains some other compounds belonging to different classes
of natural products, such as diterpenes like 7-oxocallitrisic acid
(64), picealactone C (65) and 15-hydroxy-6-en-dehydroabietic
acid (66) (Lee et al., 2009), phenolics like vanillin and 3,4dimethoxycinnamyl-3-(3,4-diacetoxyphenyl) acrylate (67) (Abd
El-Razek, 2007), acetylenes such as falcarinolone (68) (Christensen
and Brandt, 2006), sesquiterpenes like taraxacin (69) (Appendino
et al., 2006), fetidone A (70) and B (71) (Appendino et al., 2006) and
other miscellaneous compounds, such as oleic acid, -sitosterol,
galactose, arabinose, glucuronic acid, rhamnose, luteolin 7--dglucopyranoside (72) and ferulic acid (Fig. 3) (Pangarova and
Zapesochnaya, 1975; Zargari, 1996; Lee et al., 2009).
4. Pharmacology
In vitro studies: Recently, antiviral activity of asafoetida was
assessed against some human rhinovirus serotypes (Rollinger et al.,
2008). In this study, Rollinger et al. proved that cytopathic effects

in HeLa cells induced by HRV-2 (human rhinovirus) were inhibited


by asafoetida gum resin in a dose-dependent and selective manner
(Table 2). The mentioned study offers a rationalization for the use of
this gum resin in upper respiratory diseases in traditional medicine
(Lee et al., 2009).
In 2006, Kumar et al. reported a molluscicidal activity for
different root extracts of Ferula assa-foetida against the snail Lymnaea acuminata. Among the different organic extracts, the ethanol
extract was the most toxic. They concluded that the root extracts of
Ferula assa-foetida may be used as a potent molluscicide (Kumar and
Singh, 2006). They also concluded that the molluscicidal activity of
Ferula assa-foetida may be due to the ferulic acid and umbelliferone.
There are also a few anti-parasitic reports of asafoetida, including
activity against Trichomonas vaginalis (Ramadan and Al Khadrawy,
2003) and Schistosoma mansoni (Ramadan et al., 2004).
In 2004, Gowda et al. tested the antifungal activities of a series
of herbal compounds. They found that asafoetida possesses moderate antifungal properties against Aspergillus parasiticus (Gowda
et al., 2004). In a recent study, Rani et al. showed in vitro synergistic fungicidal activity of different concentrations of Ferula
assa-foetida with some unsaturated carbonyl compounds against
Sclerotium rolfsii and Macrophomina phaseolina (Rani et al., 2009).
They proved that the formulations containing Ferula assa-foetida
possessed signicant antifungal activity, justifying its application
as an antimicrobial spice. Other studies have conrmed the anti-

Table 2
Pharmacological/biological activities reported from asafoetida in detail.
Activity

Dosage form/type of extract

Concentrations/dosages

Tested living
system/organ/cell

Result(s)

Reference(s)

Anti-diabetic

Boiling water extract of


oleo-gum-resin (IP)

0.2 g/kg for 14 days

Alloxan-induced
diabetic rats (in vivo)

Abu-Zaiton (2010)

Anti-fertility

Methanol extract (oral)

400 mg/kg

Antifungal

Oleo-gum-resin

Antispasmodic

Aqueous extract of
oleo-gum-resin

0.1, 1.2 and 0.5% (w/v) of


potato dextrose agar
1, 2, 3, 5 and 7 mg/ml

SpragueDawley rats
(in vivo)
Aspergillus parasiticus

Antispasmodic

Aqueous extract of
oleo-gum-resin

3 mg/ml

Guinea-pig ileum
(in vitro)

Antitumor

Water extract of
oleo-gum-resin (oral)
Oleo-gum-resin

50 mg/animal daily for 5 days

Colloidal solution of
oleo-gum-resin (oral)
Acetone extract of
oleo-gum-resin (topical)

50 mg/kg, 60 min before


experiment
Pretreatment of animals with
300, 400 and 500 g/0.2
ml/asafoetida

Inbred strains Swiss


albino mice (in vivo)
Infected HeLa cells by
rhinovirus (in vitro)
Rat (in vivo)

Increase in body weight and insulin (from 0.33 to


0.48 ng/ml), and decrease of serum glucose (from
10.28 to 6.75 mmol/l) as compared to control
(alloxan-induced)
Prevention of pregnancy in 80% of rats, and in 100% of
rats when administered as a PVP complex
24% inhibition of Aspergillus growth in all
concentrations
Reduction of the average amplitude of the
spontaneous contractions to 83, 68, 54, 21 and 9% of
control (normal saline), respectively
Concentration-dependent relaxation in precontracted
tissues with KCl (28 mM), but no relaxatory effect in
the presence of indomethacin, propanolol, atropine
and chlorpheniramine
53% increase in life span

Cancer chemopreventive
(another study)

Oleo-gum-resin (oral)

1.25 and 2.5% in food pellets

Female
SpragueDawley rats
(in vivo)

Digestive enzyme inhibition

Oleo-gum-resin (oral)

250 mg% for 8 weeks

Rat (in vivo)

Digestive enzyme inhibition

Oleo-gum-resin (oral)

250 mg% for 8 weeks

Rat (in vivo)

Hypotensive

Aqueous extract of
oleo-gum-resin
Dried latex powder, ethanol,
chloroform, acetone and ether
extracts of dried latex powder
Resin

0.32.2 mg/100 g body weight


in 0.4 ml
70, 90, 120, 170 mg/l in
different time periods of 14, 48,
72, 96 h
On agar plate at a
concentration 200 g/ml

Anaesthetized rat
(in vivo)
Snail (in vivo)

Antiulcerogenic
Cancer chemopreventive

Molluscicidal

Mutagenic
a
b

0.7525 g/ml

Male mice (in vivo)

Salmonella
typhimurium

Inhibition of HRV-2 induced cytopathic effect


(1060%), IC50 = 10.98 g/ml
Signicant protection against gastric ulcer induced by
aspirin, 2 h cold restraint stress and 4 h pylorus ligation
Signicant increase of cutaneous antioxidants e.g.
glutathione, and signicant decrease of cutaneous
oxidative parameters e.g. xanthine oxidase, compared
to TPA-treated animals (20 nm/0.2 ml/animal)
Increase of latencya from 2.55 to 4.7 weeks in both
concentrations, decrease of tumor burdenb in each
animal from 5.45 to 3.6 (1.25%) and 2.3 (2.5%), and
decrease of tumor volume from 3.2 to 1.6 (1.25%) and
1.3 cm3 (2.5%)
Decrease the levels of phosphatase and sucrase in the
small intestine
Enhancement of pancreatic lipase activity and
stimulation of pancreatic amylase and chymotrypsin
Decreasing blood pressure from 11 mm Hg to 5 mm Hg
in a dose-dependent manner
The best results have been observed for ethanol extract
in different time periods. LC50 s were 132.31 (24 h),
111.16 (48 h), 79.7 (72 h) and 46.62 (96 h) mg/l
Active on S. typhimurium TA 1537 and inactive on S.
typhimurium TA 1538 and TA 98

Gowda et al. (2004)


Fatehi et al. (2004)

Fatehi et al. (2004)

Unnikrishnan and
Kuttan (1990)
Rollinger et al. (2008)
Agrawal et al. (2000)
Saleem et al. (2001)

Mallikarjuna et al.
(2003)

Platel and Srinivasan


(1996)
Platel and Srinivasan
(2000)
Fatehi et al. (2004)

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

Antiviral

Guinea-pig ileum
(in vitro)

Keshri et al. (1999)

Kumar and Singh


(2006)
Siwaswamy et al.
(1991)

The time of appearance of rst tumor.


Mean number of tumors/animal.

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

32
S

38

37

S S

S
44

45

S S
50

55

SH

59

40

41

S
47

S
52

51

42

S
S

S
57

56

63

60

43

48

S
54

53

OH

49 S S

36

58

S S

35

34

33

S S

46 S S

S
39

S
61

O
O
S

S
62

S
O
Fig. 2. Sulfur-containing compounds isolated from asafoetida.

fungal activity of asafoetida against some pathogenic (Kamble and


Patil, 2008; Sitara et al., 2008) and non-pathogenic fungi (Angelini
et al., 2009). There is also an old report of antibacterial activity of asafoetida against Clostridium perfringens and Clostridium
sporogenes (Garg et al., 1980). They observed 60% inhibition at the
concentration 0.1% of asafoetida in an agar plate method.
In vivo studies: In 2004, Fatehi et al. evaluated the antispasmodic
and hypotensive properties of asafoetida in animal models. They
found that asafoetida can reduce the spontaneous contraction of
the isolated guinea-pig ileum in a concentration-dependent and
reversible manner. They also showed that the gum resin is effective in reducing blood pressure in anaesthetized normotensive rats
(Table 2). In total, it was concluded that asafoetida exerts relaxant effects on vascular and ileal smooth muscles via reducing the
cytosolic Ca2+ in a non-specic way (Fatehi et al., 2004).
Post-coital antifertility is another pharmacological property
reported from Ferula assa-foetida extract. A study by Keshri et al.
revealed that the methanolic extract of Ferula assa-foetida resin
at a dose of 400 mg/kg daily on days 110 post-coitus prevented
pregnancy in 80% of adult SpragueDawley rats. They also found
that this dose inhibits pregnancy in 100% of the rats, when administered in combination with PVP (polyvinyl pyrrolidone) (Keshri
et al., 1999).
In 2010, Abu-Zaiton reported an anti-diabetic activity for
asafoetida. He showed that Ferula assa-foetida extract has protective effects in diabetes by preserving pancreatic cell integrity,

justifying its traditional uses in preventing diabetic complications


(Abu-Zaiton, 2010). He also proved that the extract reduces blood
glucose and increases insulin secretion.
There are also a few negative results of pharmacological activities of asafoetida. For example, recent investigations of the author
revealed that asafoetida (300 mg/kg) has no anticonvulsant activity in pentylenetetrazole-induced seizures in mice (Bagheri et al.,
2010). Also, previous studies showed no anti-cholestrolemic activity from asafoetida (kamanna and Chandrasekhara, 1982). In
addition, hot water extract of the plant was inactive on estrogen of
uterus, and uterus of pregnant rats, therefore, it was not considered
to be an abortifacient (Misra et al., 1969).
In spite of some old evidence about genotoxicity and mutagenicity of asafoetida (Abraham and Kesavan, 1984), recent studies
have revealed its potential antioxidant, antimutagenicity and cancer chemopreventive activities (Soudamini et al., 1995; Saleem
et al., 2001). In a recent in vivo study (Table 2), Saleem et al.
showed that pretreatment of animals with doses of 300, 400 and
500 g/200 l acetone/animal of asafoetida could cause the reversal of early events of carcinogenesis (Saleem et al., 2001). Another
study showed that asafoetida (1.25 and 2.5% (w/w) in diet) reduced
the multiplicity and size of N-methyl-N-nitrosourea-induced palpable mammary tumors in SpragueDawley rats (Mallikarjuna
et al., 2003).
Other biological activities of asafoetida are summarized in
Table 2.

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

OH

HOOC

64

O
O

COOH

65

67

OH

68

66

O
O
HO

69

O
70

71

OH
OH

HO

HO

O
OH

OH O

OH
72

Fig. 3. Miscellaneous compounds from different classes of natural products reported from asafoetida.

Toxicological studies: To our knowledge, there is no comprehensive toxicological study of asafoetida. However, a case of
methemoglobinemia has been reported after administration of
asafoetida in a 5-week-old black male infant. The infant was admitted to the hospital 6 h after the onset of tachypnea, grunting, and
cyanosis. Treatment was with intravenous methylene blue and the

infant recovered (Kelly et al., 1984). The intake of larger dosages can
lead to swelling of the lips, digestive complaints such as atulence
and diarrhea, discomfort and headache. Swelling of the genital
organs has been observed following external administration on
the abdomen. It is not recommended to be used during pregnancy
(Emami et al., 2010).

Table 3
Biological activities reported from the bioactive coumarins of asafoetida.
Compound number

Compound name

Biological activities

Reference(s)

Antiviral (inuenza H1 N1 ), NF-B inhibitor

Appendino et al. (2006), Lee et al. (2009)

Antiviral (inuenza H1 N1 )

Lee et al. (2009)

29
13

8-Acetoxy-5-Shydroxyumbelliprenin
10-R-acetoxy-11hydroxyumbelliprenin
epi-Conferdione
Conferol

Lee et al. (2009)


Behnam Rassouli et al. (2009), Lee et al. (2009)

9
10
11

Farnesiferol A
Farnesiferol B
Farnesiferol C

Antiviral (inuenza H1 N1 )
Antiviral (inuenza H1 N1 ), Cytotoxic (HepG2, Hep3B and
MCF-7), synergistic effect with anticancer agents
(vincristine)
Antiviral (inuenza H1 N1 )
Antiviral (inuenza H1 N1 , HRV-2)
Antiviral (inuenza H1 N1 , HRV-2), antiangiogenic,
antitumor
Molluscicidal, anticoagulant, antioxidant (as sodium
ferulate), cancer chemopreventive, anti-atherosclerotic,
angiogenesis inducer, neuroprotective, antigenotoxic,
vasodilator, hypoglycemic

6
23

Ferulic acid

12

Galbanic acid

24
28
25

10-R-karatavicinol
Ligupersin A
Methyl galbanate
Umbelliferone

Umbelliprenin

Antiviral (inuenza H1 N1 , HRV-2), bacterial resistance


modulator (Staphylococcus aureus), antileishmanial
Antiviral (inuenza H1 N1 )
Antiviral (inuenza H1 N1 )
Antiviral (inuenza H1 N1 )
Molluscicidal, antioxidant, antihyperglycemic,
antihyperlipidemic, antioedema
Anti-inammatory, 5-lipoxygenase inhibitor, cancer
chemopreventive (in vitro and in vivo), apoptosis inducer
(Melanoma cell line), depigmentation of bacteria (Serratia
marcescens), antileishmanial

Lee et al. (2009)


Lee et al. (2009), Rollinger et al. (2008)
Lee et al. (2009, 2010), Rollinger et al. (2008)
Balakrishnan et al. (2008), Baskaran et al.
(2010), Cheng et al. (2008), Eun et al. (2007),
Kwon et al. (2009), Lin et al. (2010), Lu et al.
(1998), Pradeep et al. (2009), Suzuki et al.
(2007), Wang et al. (2008)
Iranshahi et al. (2007), Lee et al. (2009),
Rollinger et al. (2008), Shahverdi et al. (2007)
Lee et al. (2009)
Lee et al. (2009)
Lee et al. (2009)
Lino et al. (1997), Pradeep et al. (2009), Ramesh
and Pugalendi (2005, 2006), Singh et al. (2010)
Barthomeuf et al. (2008), Iranshahi et al.
(2007), Iranshahi et al. (2009a,b, 2008, 2004)

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

4.1. Bioactive compounds


Most of the bioactive compounds reported from asafoetida,
belong to the sesquiterpene coumarins class. Umbelliprenin is
the rst sesquiterpene coumarin that is synthesized by the
plant Ferula assa-foetida. There are a number of biological activities that have been reported for this compound, including
cancer chemoprevention (Iranshahi et al., 2008, 2009b), apoptosis induction in a melanoma cell line (Barthomeuf et al.,
2008), 5-lipoxygenase inhibition (Iranshahi et al., 2009a), antiinammatory action (Iranshahi et al., 2009a) and depigmentation
of Serratia marcescens (Iranshahi et al., 2004). Other bioactive
sesquiterpene coumarins include galbanic acid, 8-acetoxy-5-Shydroxyumbelliprenin, farnesiferol A, farnesiferol B, farnesiferol C,
10-R-acetoxy-11-hydroxyumbelliprenin, 10-R-karatavicinol, conferol, etc. For simplicity, biological activities of the mentioned
sesquiterpene coumarins are summarized in Table 3. However,
it should be pointed out that these sesquiterpene coumarins are
not exclusive to asafoetida. The compounds occur in other plants,
particularly in other Ferula species. For this reason, some of these
biological activities have been reported for plants with different
origins.

5. Discussion and conclusion


Although asafoetida has been reported to be obtained from different sources, Ferula assa-foetida is considered to be the main
source of asafoetida. This plant is native to central Asia, particularly eastern Iran and Afghanistan, from where it is exported to the
rest of the world. Although asafoetida is not native to India, it has
been used in Indian medicine and cookery for ages. In addition, it
has been used in traditional medicine of other countries such as
Malaysia, Nepal and Fiji.
New pharmacological studies have almost conrmed the traditional uses of asafoetida as an antihelminthic, antispasmodic
and antibacterial agent. In addition, there is a correlation between
some traditional uses of asafoetida and those of new studies. For
example, modern phytochemical and pharmacological studies have
been revealed that umbelliprenin (1) is one of the major components of asafoetida possessing strong lipoxygenase inhibitory
activity (IC50 = 0.0725 M) (Iranshahi et al., 2009a). Regarding
lipoxygenases inhibition as one of approaches to treat asthma,
this offers a rationalization for the traditional use of asafoetida
in the treatment of asthma. Currently, anti-asthma activity of
asafoetida and umbelliprenin is investigated by the author and his
colleagues.
Another biological activity of asafoetida, which has been conrmed by a number of new studies, is cancer chemoprevention
(Saleem et al., 2001; Mallikarjuna et al., 2003). Different mechanisms seem to impact on this activity such as radical scavenging
activity of sulfur-containing compounds, lipoxygenase inhibition
by umbelliprenin and its derivatives, increase in the activity of
endogenous antioxidants and decrease in oxidative parameters. In a
study, it has been shown that asafoetida inhibits microsomal activation dependent mutagenicity of 2-acetamidoourene. The results
indicated that asafoetida may ameliorate the effect of environmental mutagens especially present in the food (Kochhar, 2008).
Umbelliprenin has also been shown to have remarkable cancer
chemoprevention in vitro and in vivo (Iranshahi et al., 2008, 2009b).
In an in vivo study, we assessed the cancer chemopreventive activity of umbelliprenin in vivo by using a two-stage carcinogenesis
assay of mouse skin tumors induced by peroxynitrite as an initiator
and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter.
We found that cancer chemoprevention of umbelliprenin is comparable with curcumin, a well-known cancer chemopreventive agent

(Iranshahi et al., 2009b). Blocking the enzyme 5-lipoxygenase may


be plausible mechanism accounting for at least part of the observed
chemopreventive activity of umbelliprenin. It seems that umbelliprenin might be a lead compound to design and synthesize new
derivatives with higher potency and more safety.
Recent in vivo study (Fatehi et al., 2004) has shown an antispasmodic activity that provides convincing support for the traditional
use of asafoetida as an antispasmodic agent. In the study, Fatehi
et al. used a water extract of oleo-gum-resin at the concentrations 1, 2, 3, 5 and 7 mg/ml on guinea-pig ileum (for more details
see Table 2). They observed a signicant reduction in the average amplitude of the spontaneous contractions. However, it should
be pointed out that a water extract of asafoetida does not necessarily include all active components of the whole oleo-gum-resin.
The water-insoluble fraction of this oleo-gum-resin may also have
potential antispasmodic components. Therefore, it seems there is
a need to evaluate the whole oleo-gum-resin for antispasmodic
activity which is emphasized in traditional medicines of different
countries.
Antihelminthic property (or anthelmintic) is another emphatically reported traditional use of asafoetida in different countries.
In Iran, China and Nepal, it is traditionally used for infestation with
intestinal parasites (Zargari, 1996; Ross, 2005; Emami et al., 2010).
There is no study regarding this important activity of asafoetida.
However the evaluation of its antihelminthic activity is something
that warrants further investigation.
In 2009, Lee et al. evaluated antiviral activity of sesquiterpene
coumarins from asafoetida against inuenza H1 N1 . Among tested
sesquiterpene coumarins, galbanic acid (12, IC50 = 0.26 g/ml),
farnesiferol C (11, IC50 = 0.29 g/ml) and epi-conferdione (29,
IC50 = 0.32 g/ml) exhibited the best potency, comparable to
amantadine (IC50 = 0.92 g/ml) as an antiviral standard. These compounds may also serve as promising lead compounds for new
drug development against viral infections, particularly inuenza
and common cold (Lee et al., 2009). Asafoetida is a complex mixture of these compounds and may exert more pronounced effects
than individual compounds. The antiviral activity of asafoetida, a
complex mixture of various antiviral compounds, needs to be investigated in clinical trials or in vivo studies. However, the aforesaid
evidence offer a rationalization for the traditional uses of asafoetida
in the treatment of upper respiratory diseases.
It should be pointed out, however, a number of pharmacological
surveys, carried out on asafoetida (Table 2), used a water extract
of asafoetida that is not the most common application form of
asafoetida. As mentioned above, the aqueous extract does not certainly include non-polar components or even some of the active
components of the whole oleo-gum-resin.
To date, one study has only addressed potential toxicity of
asafoetida in a case report (Kelly et al., 1984). There is a need to
study the acute toxicity, sub acute toxicity, chronic toxicity and
safety proling of asafoetida. However, detailed animal toxicity
studies of asafoetida and their compounds are required prior to
clinical trials.
It is strongly believed that detailed information as presented
in this review on the phytochemical and biological activities of
asafoetida provides detailed evidence for the use of this plant in
different medicines. Regarding the rich background of biological
activities of asafoetida, it seems there are still a large number
of unaccomplished investigations, particularly clinical trials of
asafoetida and its bioactive compounds.

Acknowledgments
We would like to thank Dr. Seyyed Ahmad Emami and Dr. Javad
Asili for their scientic consulting and kind help.

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110

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