Asafoetida

Journal of Ethnopharmacology 134 (2011) 110

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Journal of Ethnopharmacology

journa l homepage: www.e lsev ier .com/

Review

Traditional uses, phytochemistry and pharmacolo(Feru

MiladBiotechnol ad,

a r t i

Article history:Received 1 July 2010Received in reAccepted 26 NAvailable onlin

Keywords:ApiaceaeAsafoetidaFerula assa-foeOleo-gum-resiSesquiterpene

The old traditional phytomedicine asafoetida, an oleo-gum-resin obtained from the roots of different

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12. Traditional uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

3.1. Coumarins and sesquiterpene coumarins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23.2.3.3.

4. Pharm4.1.

5. DiscuAcknoRefer

1. Introdu

Asafoetithe rootsofThis speciessource of asfoetida, Ferunarthex, are

CorresponResearch Cent(MUMS), P.O. Bfax: +98 511 8

E-mail add

0378-8741/$ doi:10.1016/j.Sulfur-containing compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Other compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4acology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Bioactive compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

ssion and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8wledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

ences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

ction

da is an oleo-gum-resin obtained from the exudates ofthe Iranianendemicmedicinal plant, Ferula assa-foetida.(Ferula assa-foetida) is often considered to be the mainafoetida, although other Ferula species, such as Ferulala rubricaulis, Ferula rigidula, Ferula alliacea and Ferulaalso sources of asafoetida (Rajanikanth et al., 1984;

ding author at: Department of Pharmacognosy, Biotechnologyer and School of Pharmacy, Mashhad University of Medical Sciencesox 91775-1365, Mashhad, Iran. Tel.: +98 511 8823255/66;

823251.ress: [email protected] (M. Iranshahi).

Takeoka, 2001; Evans, 2002). Ferula assa-foetida grows wildly inthe central and southern mountains of Iran. The oleo-gum-resinasafoetida is called Anghouzeh, Khorakoma and Anguzakomain Iran. Other names in some different languages are shown inTable 1. The plant, which belongs to the Apiaceae family, is anherbaceous perennial with an unpleasant odor that grows to about2m in height. The oleo-gum-resin is often obtained by incision ofthe roots or removal of the stems. Hardened exudates (oleo-gum-resin) are then collected and packed for export. Asafoetida occursin two principle forms, tears and mass. Mass is the most commonform of asafoetida in the market (Tyler et al., 1976; Evans, 2002).

Asafoetida has been used as a spice and a folk phytomedicinefor centuries. Asafoetida has a characteristic sulfurous odor anda bitter taste. It is used as a avoring spice in a variety of foods,

see front matter 2010 Elsevier Ireland Ltd. All rights reserved.jep.2010.11.067vised form 18 October 2010ovember 2010e 3 December 2010

tidancoumarins

Ferula assa-foetida, is used in different countries for various purposes. Asafoetida is not only used as aculinary spice but also traditionally used to treat various diseases, including asthma, gastrointestinal dis-orders, 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 includ-ing sugars, sesquiterpene coumarins and polysuldes have been isolated from this plant. Recent studieshave shown new promising antiviral sesquiterpene coumarins from this old phytomedicine. The presentreview summarizes the information concerning the traditional uses, phytochemistry andbiological activ-ities of asafoetida.

2010 Elsevier Ireland Ltd. All rights reserved.locate / je thpharm

gy of asafoetida

Iranla assa-foetida oleo-gum-resin)A review

Iranshahy, Mehrdad Iranshahi

ogy Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashh

c l e i n f o a b s t r a c t

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

Table 1Various names of asafoetida in some different languages.

Language Name

AfghanArabicChineseDutchEnglishFinnishFrenchGermanHindiHungarianItalianNepaliPakistanPolishRussianSpanishSwedishTurkish

particularlysume it inaphrodisiac1990; Bandthe treatmstomachachinuenza (Z2009). Receshown seveantiviral (L2008; AngeSivaramakrZaiton, 201(Fatehi et afrom this ol

Along wber of phytPangarovaBuddrus etNassar et aet al., 20012005; AppeEl-Razek, 2and Hasanlincluding r(Takeoka, 2esters, coumThe gum incuronic acifraction conother volatiasafoetida htive composesquiterpeamantadine

The presistry, and preview incl

2. Traditio

We clasasafoetida.

Gastroinas a valuab

roasted in ghee (a claried butter without any solid milk parti-cles or water) is usually used in gastrointestinal disorders becauseunprocessed asafoetida causes irritation and inammation (Gogte,2000). It is also used for the treatment of stomachache in the east-

ion oasafosmo

t of tr andian flminxatioral

ful astati

extrat stovousle remanis

for hEigneIn Irt (Zaco (Rbrainpiratonaltida iginatida ioniaant (nally2005edicistan2005cemeenti

otenies sisiacpite osump006)mach010)Kama, AnguzaShajarat-ul-Heltit, AngudnA-weiDuivelsdrekAsafetida, Stinking assa, Devils dungPirunpaska, PirunpihkaAse-ftideStinkender assand, TeufelsdreckHing, HinguOrdoggyokerAsa fetidaHing, HinguKama, AnguzaZapaliczka Cuchnaca, AsafetidaAsafetidaAsaftidaDyvelstrckSeytan tersi, Seytan boku, Seytanotu

in India. In addition, Nepali people regularly con-their daily diets, and it is believed that asafoetida has, sedative and diuretic properties (Eigner and Scholz,yopadhyay et al., 2006). It is traditionally used forent of different diseases, such as asthma, epilepsy,e, atulence, intestinal parasites, weak digestion andargari, 1996; Takeoka, 2001; Evans, 2002; Lee et al.,nt pharmacological and biological studies have alsoral activities, such as antioxidant (Dehpour et al., 2009),ee et al., 2009), antifungal (Singh, 2007; Sitara et al.,lini et al., 2009), cancer chemopreventive (Aruna andishnan, 1992; Saleem et al., 2001), anti-diabetic (Abu-0), antispasmodic (Fatehi et al., 2004), hypotensivel., 2004), and molluscicidal (Kumar and Singh, 2006)eo-gum-resin.ith these biological surveys, there have been a num-ochemical investigations of asafoetida (Mahran, 1973;and Zapesochnaya, 1975; Rajanikanth et al., 1984;al., 1985; Banerji et al., 1988; Kajimoto et al., 1989;l., 1995; Nassar and Mohamed, 1998; Abd El-Razek; Takeoka, 2001; Duan et al., 2002; Khajeh et al.,ndino et al., 2006; Bandyopadhyay et al., 2006; Abd007; Ghosh et al., 2009; Lee et al., 2009; Mirzaeioo, 2009). Asafoetida consists of three main fractions,esin (4064%), gum (25%) and essential oil (1017%)001). The resin fraction contains ferulic acid and itsarins, sesquiterpene coumarins and other terpenoids.

cludes glucose, galactose, l-arabinose, rhamnose, glu-

ern regIndia,antispaextrac(EigneIn Iranantihemild lapeoplepowerfor infewaterof upse

NervaluabIn Afghorallyspice (2006).vulsanMorocto the

Restraditiasafoefor anasafoepneumstimulmedici(Ross,as a mAfghan(Ross,a replaaforemcough.

Impcountraphrod

In sits conet al., 2the stoet al., 2d, polysaccharides and glycoproteins, and the volatiletains sulfur-containing compounds,monoterpenes andle terpenoids. Bioassay-guided fractionation studies ofave led to the identication of some interesting bioac-unds; for example, Lee et al. characterized antiviralne coumarins fromasafoetida that aremorepotent thanagainst inuenza A (Lee et al., 2009).

ent review deals with the traditional uses, phytochem-harmacological studies of asafoetida. In addition, thisudes bioactive compounds isolated from asafoetida.

nal uses

sied the traditional uses according to similar uses of

testinal disorders: In Ayurveda, asafoetida is introducedle remedy for atulence (Kapoor, 2001). Asafoetida

It seemupper respbronchitistrointestinaantispasmo

3. Phytoch

3.1. Couma

Tsukervplants of this a genus r(Abd El-Razhave beensesquiterpevariation inf Shimoga of India (Rajakumar and Shivanna, 2009). Inetida is traditionally used as an antibacterial agent, andic, a diuretic and a laxative (Srinivasan, 2005). Waterhe dried gum is also taken orally as an antihelminthicScholz, 1990; Ross, 2005; Bandyopadhyay et al., 2006).olk medicine, asafoetida is used as an antispasmodic,thic, and carminative agent. In addition, it is used as ave medicine for the elderly (Zargari, 1996). Americanly use it as an antihelminthic and it is claimed to be antispasmodic (Ross, 2005). In China, asafoetida is usedon with intestinal parasites (Emami et al., 2010). In Fiji,ct of the dried gum is also taken orally for the treatmentmach (Ross, 2005).disorders: In Ayurveda, asafoetida is introduced as aedy for hysteria andnervous disorders (Kapoor, 2001).

tan, hot water extract of the dried gum is also takenysteria. Nepali people use it as a sedative and a diureticr and Scholz, 1990; Ross, 2005; Bandyopadhyay et al.,anian folk medicine, asafoetida is used as an anticon-rgari, 1996) as well as it is chewed as an antiepileptic inoss, 2005). American people orally use it as a stimulantand nerves (Ross, 2005).

ory problems: Apparently, one of the most importantuses of asafoetida is the treatment of asthma. In India,s traditionally used as a useful symptomatic treatmentpectoris and asthma (Srinivasan, 2005). In Ayurveda,s introduced as a valuable remedy for whooping cough,and bronchitis in children. It is also a pulmonary

Kapoor, 2001). In Saudi Arabia, dried asafoetida isused for whooping cough, asthma, and bronchitis

). In Iranian folk medicine, asafoetida is also usedine for the treatment of asthma (Zargari, 1996). Inand Fiji, the dried gum is taken for whooping cough

). In ancient Rome, it was used as a culinary spice and asnt for Silphion cyrenaicum (Appendino et al., 2006). The

oned plant has been used for tuberculosis and incessant

ce: In Ayurveda and traditional medicines of differentuch as America and Brazil, it is considered to be an(Kapoor, 2001; Ross, 2005).f various applicationsof asafoetida indifferent cultures,tion is forbidden in traditional Korean Buddhism (Kim. In homeopathy, asafoetida is used for low acid levels in, stomach pressure, atulence and loose stools (Emami.s that the most frequent uses of asafoetida are iniratory diseases, including the treatment of asthma,and whooping cough (as an expectorant), and gas-l disorders as an antihelminthic, anti-atulence anddic.

emistry

rins and sesquiterpene coumarins

anik et al. was the rst group to begin to investigatee genus Ferula in 1935 (Abd El-Razek et al., 2003). Ferulaich in coumarins, particularly sesquiterpene coumarinsek et al., 2003). To date, many sesquiterpene coumarinsidentied from this genus. A large number of differentne coumarins have been reported from asafoetida. Thethe structures of reported sesquiterpene coumarins

M. Iranshahy, M. Iranshahi / Journal of Ethnopharmacology 134 (2011) 110 3

may be due to their different sources. In Fig. 1, the chemical struc-tures of sesquiterpene coumarins that have been reported to dateare depicted.

Sesquiterpene coumarins of Ferula assa-foetida include umbel-liprenin (1), 5-hydroxyumbelliprenin (2), 8-hydroxyumbelliprenin(3), tadshiferin (4), asacoumarin A (5), 8-acetoxy-5-S-hydroxyumbelliprenin (6), asacoumarin B (7) (the structureof this compound was revised later and it was revealed that itsstructure is the same as that of galbanic acid), assafoetidin (8),franesiferol A (9), franesiferol B (10), franesiferol C (11), galbanicacid (12), conferol (13), gummosin (14), assafoetidinol A (15) andassafoetidinol 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 Ferulaassa-foetida are ferocaulicin (17), epi-samarcandin (18), epi-samarcandin 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 theisolation 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), ligupersinA (28), epi-conferdione (29),microlobin(30), polyanthinin (31) and umbelliferone (7-hydroxycoumarin)(Buddrus et al., 1985; Abd El-Razek et al., 2001; Bandyopadhyayet al., 2006).

3.2. Sulfur-containing compounds

These compounds play an important role in the odor and tasteof asafoetida. Three major sulfur constituents that have been iden-tied in Ferula assa-foetida include 2-butyl 1-propenyl disulde(32), 1-(methylthio)propyl 1-propenyl disulde (33) and 2-butyl3-(methylthio)-2-propenyl disulde (34) (Takeoka, 2001).

Some other sulfur constituents include 2-methyl-2-propanethiol (35), 2,3-dimethylthiirane (36), 1-methylthio-(Z)-1-propene (37), 1-methylthio-(E)-1-propene (38), dimethyl disul-de (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), 2,3,4-trimethylthiophene (58), 2-butyl vinyl disulde (49), 2-butyl ethyldisulde (50), 2-butyl propyl disulde (51), 2-butyl 1-propenyldisulde (52), methyl 1-(methylthio)propyl disulde (53), di-2-butyl disulde (54), methyl 1-(methylthio)ethyl disulde (55),1-(methylthio)propyl propyl disulde (56), 1-(methylthio)propyl1-propenyl disulde (57) (Takeoka, 2001) and asadisulde (58)(Kajimoto et al., 1989). Asafoetida also contains 2-butyl methyltrisulde (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 polysul-de derivatives of asafoetida (Lee et al., 2009). These compounds

OO O

1 R1= R2 =R3= H

2 R1= OH, R2=R3= H

3 R1=R3= H, R2= OH

4 R1=R2= H, R3= OH

5 R1=R2= OH, R3 = H

O

HO

O O

O

HO

O O

COOH

O O O

7

O

8

10H

O O

R1

R2

9 R1= OH, R2 = H

O

O

R1

R2

R3

d from6 R1= OH, R2= OAc, R3= H

O O O

OHOOC

1211

14 R1 = H, R2 = OH

HOH

R1

R2 R3

O O

15 R1= OH, R2=R3= H

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

O

O

17

O

AcO

O

Fig. 1. Sesquiterpene coumarins isolateO

H

O O

13

O

O

R1R3

R2

R4

OO

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

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

O

HO

asafoetida.


OO O

O

OO

OO O

O

H

O

have also bal., 2002).

3.3. Other c

The comsesquiterpecontains soof natural p(64), piceaacid (66)dimethoxycEl-Razek, 20and Brandtet al., 2006)other miscegalactose, aglucopyranZapesochna

4. Pharma

In vitroassessed ag2008). In thOH

H

20HO

21HOO

OO O

HO

OAc 23

O

HO

OH 24

OO O

HO26

H

OO O

27 HHOOH

O

O O O

29AcOOH

H

O

OO O

30

Fig. 1. (Continued )

een reported from the roots of Ferula foetida (Duan et

ompounds

pounds of Ferula assa-foetida are not limited tone coumarins and sulfur-containing compounds; it alsome other compounds belonging to different classesroducts, such as diterpenes like 7-oxocallitrisic acid

lactone C (65) and 15-hydroxy-6-en-dehydroabietic(Lee et al., 2009), phenolics like vanillin and 3,4-innamyl-3-(3,4-diacetoxyphenyl) acrylate (67) (Abd07), acetylenes such as falcarinolone (68) (Christensen

, 2006), sesquiterpenes like taraxacin (69) (Appendino, fetidone A (70) and B (71) (Appendino et al., 2006) andllaneous compounds, such as oleic acid, -sitosterol,rabinose, glucuronic acid, rhamnose, luteolin 7--d-oside (72) and ferulic acid (Fig. 3) (Pangarova andya, 1975; Zargari, 1996; Lee et al., 2009).

cology

studies: Recently, antiviral activity of asafoetida wasainst somehuman rhinovirus serotypes (Rollinger et al.,is study, Rollinger et al. proved that cytopathic effects

in HeLa cellby asafoetid(Table 2). Ththis gum re(Lee et al., 2

In 2006different ronaea acumiextractwasFerulaassa-Singh, 2006Ferula assa-There are aactivity aga2003) and S

In 2004,of herbal coerate antifuet al., 2004ergistic funassa-foetidaSclerotium rThey provepossessed sas an antimH22

O O

3COOC

O O

25

HO

O O O

28H

O O O

31

s induced by HRV-2 (human rhinovirus) were inhibiteda gum resin in a dose-dependent and selective mannerementioned study offers a rationalization for the use of

sin in upper respiratory diseases in traditionalmedicine009)., Kumar et al. reported a molluscicidal activity forot extracts of Ferula assa-foetida against the snail Lym-nata. Among the different organic extracts, the ethanolthemost toxic. They concluded that the root extracts offoetidamaybeusedasapotentmolluscicide (Kumarand). They also concluded that the molluscicidal activity offoetidamaybedue to the ferulic acid andumbelliferone.lso a few anti-parasitic reports of asafoetida, includinginst Trichomonas vaginalis (Ramadan and Al Khadrawy,chistosoma mansoni (Ramadan et al., 2004).Gowda et al. tested the antifungal activities of a seriesmpounds. They found that asafoetida possesses mod-ngal properties against Aspergillus parasiticus (Gowda). In a recent study, Rani et al. showed in vitro syn-gicidal activity of different concentrations of Ferulawith some unsaturated carbonyl compounds againstolfsii and Macrophomina phaseolina (Rani et al., 2009).d that the formulations containing Ferula assa-foetidaignicant antifungal activity, justifying its applicationicrobial spice. Other studies have conrmed the anti-

M.Iranshahy,M

.Iranshahi/JournalofEthnopharmacology

134 (2011) 1105

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

Activity Dosage form/type of extract Concentrations/dosages Tested livingsystem/organ/cell

Result(s) Reference(s)

Anti-diabetic Boiling water extract ofoleo-gum-resin (IP)

0.2 g/kg for 14 days Alloxan-induceddiabetic rats (in vivo)

Increase in body weight and insulin (from 0.33 to0.48ng/ml), and decrease of serum glucose (from10.28 to 6.75mmol/l) as compared to control(alloxan-induced)

Abu-Zaiton (2010)

Anti-fertility Methanol extract (oral) 400mg/kg SpragueDawley rats(in vivo)

Prevention of pregnancy in 80% of rats, and in 100% ofrats when administered as a PVP complex

Keshri et al. (1999)

Antifungal Oleo-gum-resin 0.1, 1.2 and 0.5% (w/v) ofpotato dextrose agar

Aspergillus parasiticus 24% inhibition of Aspergillus growth in allconcentrations

Gowda et al. (2004)

Antispasmodic Aqueous extract ofoleo-gum-resin

1, 2, 3, 5 and 7mg/ml Guinea-pig ileum(in vitro)

Reduction of the average amplitude of thespontaneous contractions to 83, 68, 54, 21 and 9% ofcontrol (normal saline), respectively

Fatehi et al. (2004)

Antispasmodic Aqueous extract ofoleo-gum-resin

3mg/ml Guinea-pig ileum(in vitro)

Concentration-dependent relaxation in precontractedtissues with KCl (28mM), but no relaxatory effect inthe presence of indomethacin, propanolol, atropineand chlorpheniramine


Antitumor Water extract ofoleo-gum-resin (oral)

50mg/animal daily for 5 days Inbred strains Swissalbino mice (in vivo)

53% increase in life span Unnikrishnan andKuttan (1990)

Antiviral Oleo-gum-resin 0.7525g/ml Infected HeLa cells byrhinovirus (in vitro)

Inhibition of HRV-2 induced cytopathic effect(1060%), IC50 = 10.98g/ml

Rollinger et al. (2008)

Antiulcerogenic Colloidal solution ofoleo-gum-resin (oral)

50mg/kg, 60min beforeexperiment

Rat (in vivo) Signicant protection against gastric ulcer induced byaspirin, 2h cold restraint stress and 4h pylorus ligation

Agrawal et al. (2000)

Cancer chemopreventive Acetone extract ofoleo-gum-resin (topical)

Pretreatment of animals with300, 400 and 500g/0.2ml/asafoetida

Male mice (in vivo) Signicant increase of cutaneous antioxidants e.g.glutathione, and signicant decrease of cutaneousoxidative parameters e.g. xanthine oxidase, comparedto TPA-treated animals (20nm/0.2ml/animal)

Saleem et al. (2001)

Cancer chemopreventive(another study)

Oleo-gum-resin (oral) 1.25 and 2.5% in food pellets FemaleSpragueDawley rats(in vivo)

Increase of latencya from 2.55 to 4.7 weeks in bothconcentrations, decrease of tumor burdenb in eachanimal from 5.45 to 3.6 (1.25%) and 2.3 (2.5%), anddecrease of tumor volume from 3.2 to 1.6 (1.25%) and1.3 cm3 (2.5%)

Mallikarjuna et al.(2003)

Digestive enzyme inhibition Oleo-gum-resin (oral) 250mg% for 8 weeks Rat (in vivo) Decrease the levels of phosphatase and sucrase in thesmall intestine

Platel and Srinivasan(1996)

Digestive enzyme inhibition Oleo-gum-resin (oral) 250mg% for 8 weeks Rat (in vivo) Enhancement of pancreatic lipase activity andstimulation of pancreatic amylase and chymotrypsin

Platel and Srinivasan(2000)

Hypotensive Aqueous extract ofoleo-gum-resin

0.32.2mg/100g body weightin 0.4 ml

Anaesthetized rat(in vivo)

Decreasing blood pressure from 11mmHg to 5mmHgin a dose-dependent manner


Molluscicidal Dried latex powder, ethanol,chloroform, acetone and etherextracts of dried latex powder

70, 90, 120, 170mg/l indifferent time periods of 14, 48,72, 96h

Snail (in vivo) The best results have been observed for ethanol extractin different time periods. LC50s were 132.31 (24h),111.16 (48h), 79.7 (72h) and 46.62 (96h)mg/l

Kumar and Singh(2006)

Mutagenic Resin On agar plate at aconcentration 200g/ml

Salmonellatyphimurium

Active on S. typhimurium TA 1537 and inactive on S.typhimurium TA 1538 and TA 98

Siwaswamy et al.(1991)

a The time of appearance of rst tumor.b Mean number of tumors/animal.


SS SS

SS

SS

SH S

S

SS

32 33 34 3635

41

7

fungal activPatil, 2008;et al., 2009ity of asafosporogenesconcentrati

In vivo stand hypotefound thatthe isolatedreversible mtive in redu(Table 2). Iant effectscytosolic Ca

Post-coireported frrevealed that a dose opregnancythat this doistered in cet al., 1999)

In 2010asafoetida.tective effeSS S

SO

S

SS S

SS

SS

SSS

SS

S

S SS S

S

SS

S

S

SS

S SS S S SSS

37 38 39 40

44 45 46 4

50 51 52

55 56 57

59

60 61

SS

OSO63

Fig. 2. Sulfur-containing compounds isolated fro

ity of asafoetida against some pathogenic (Kamble andSitara et al., 2008) and non-pathogenic fungi (Angelini). There is also an old report of antibacterial activ-etida against Clostridium perfringens and Clostridium(Garg et al., 1980). They observed 60% inhibition at theon 0.1% of asafoetida in an agar plate method.udies: In 2004, Fatehi et al. evaluated the antispasmodicnsive properties of asafoetida in animal models. Theyasafoetida can reduce the spontaneous contraction ofguinea-pig ileum in a concentration-dependent andanner. They also showed that the gum resin is effec-

cing blood pressure in anaesthetized normotensive ratsn total, it was concluded that asafoetida exerts relax-on vascular and ileal smooth muscles via reducing the2+ in a non-specic way (Fatehi et al., 2004).tal antifertility is another pharmacological propertyom Ferula assa-foetida extract. A study by Keshri et al.at the methanolic extract of Ferula assa-foetida resinf 400mg/kg daily on days 110 post-coitus preventedin 80% of adult SpragueDawley rats. They also foundse inhibits pregnancy in 100% of the rats, when admin-ombination with PVP (polyvinyl pyrrolidone) (Keshri., Abu-Zaiton reported an anti-diabetic activity forHe showed that Ferula assa-foetida extract has pro-cts in diabetes by preserving pancreatic cell integrity,

justifying it(Abu-Zaitonglucose and

There arties of asaforevealed thity in penty2010). Alsoity from aaddition, houterus, andto be an abo

In spitegenicity of ahave revealcer chemopet al., 2001showed tha500g/200sal of earlystudy showthe multiplpable mamet al., 2003)

Other bTable 2.S S S

S SS

SS

S SS

42 43

48 49

53 54

SS

58

O

O

OH

SS

SO62

m asafoetida.

s traditional uses in preventing diabetic complications, 2010). He also proved that the extract reduces bloodincreases insulin secretion.

e also a few negative results of pharmacological activi-etida. For example, recent investigations of the authorat asafoetida (300mg/kg) has no anticonvulsant activ-lenetetrazole-induced seizures in mice (Bagheri et al.,, previous studies showed no anti-cholestrolemic activ-safoetida (kamanna and Chandrasekhara, 1982). Int water extract of the plant was inactive on estrogen ofuterus of pregnant rats, therefore, it was not consideredrtifacient (Misra et al., 1969).of some old evidence about genotoxicity and muta-safoetida (Abraham and Kesavan, 1984), recent studiesed its potential antioxidant, antimutagenicity and can-reventive activities (Soudamini et al., 1995; Saleem). In a recent in vivo study (Table 2), Saleem et al.t pretreatment of animals with doses of 300, 400 andl acetone/animal of asafoetida could cause the rever-events of carcinogenesis (Saleem et al., 2001). Anothered that asafoetida (1.25 and 2.5% (w/w) in diet) reducedicity and size of N-methyl-N-nitrosourea-induced pal-mary tumors in SpragueDawley rats (Mallikarjuna.iological activities of asafoetida are summarized in


O

O

O

O

O

OO

O O

OH

HOOCO

64O

65OO

COOH 66

OH

67

68

O

O

O

6970

OO

71

HOO

OOH

O

OHOH

O

OHOH

HO

OHO

72

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

Toxicologhensive toxmethemoglasafoetida ited to the hcyanosis. Tr

recovswearrhehasomei et a

Table 3Biological acti

Compound n

6

23

2913

91011

12

242825

1ical studies: To our knowledge, there is no compre-icological study of asafoetida. However, a case ofobinemia has been reported after administration ofn a 5-week-old blackmale infant. The infantwas admit-ospital 6h after the onset of tachypnea, grunting, andeatment was with intravenous methylene blue and the

infantlead toand diorgansthe abd(Emamvities reported from the bioactive coumarins of asafoetida.

umber Compound name Biological activities

8-Acetoxy-5-S-hydroxyumbelliprenin

Antiviral (inuenza H1N1), NF-B inhibitor

10-R-acetoxy-11-hydroxyumbelliprenin

Antiviral (inuenza H1N1)

epi-Conferdione Antiviral (inuenza H1N1)Conferol Antiviral (inuenza H1N1), Cytotoxic (HepG2,

MCF-7), synergistic effect with anticancer age(vincristine)

Farnesiferol A Antiviral (inuenza H1N1)Farnesiferol B Antiviral (inuenza H1N1, HRV-2)Farnesiferol C Antiviral (inuenza H1N1, HRV-2), antiangiog

antitumorFerulic acid Molluscicidal, anticoagulant, antioxidant (as s

ferulate), cancer chemopreventive, anti-atherangiogenesis inducer, neuroprotective, antigevasodilator, hypoglycemic

Galbanic acid Antiviral (inuenza H1N1, HRV-2), bacterial remodulator (Staphylococcus aureus), antileishm

10-R-karatavicinol Antiviral (inuenza H1N1)Ligupersin A Antiviral (inuenza H1N1)Methyl galbanate Antiviral (inuenza H1N1)Umbelliferone Molluscicidal, antioxidant, antihyperglycemic

antihyperlipidemic, antioedemaUmbelliprenin Anti-inammatory, 5-lipoxygenase inhibitor,

chemopreventive (in vitro and in vivo), apopto(Melanoma cell line), depigmentation of bactemarcescens), antileishmanialered (Kelly et al., 1984). The intake of larger dosages canlling of the lips, digestive complaints such as atulencea, discomfort and headache. Swelling of the genitalbeen observed following external administration onn. It is not recommended to be used during pregnancyl., 2010).Reference(s)

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

Lee et al. (2009)

Lee et al. (2009)Hep3B andnts

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

Lee et al. (2009)Lee et al. (2009), Rollinger et al. (2008)

enic, Lee et al. (2009, 2010), Rollinger et al. (2008)

odiumosclerotic,notoxic,

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)

sistanceanial

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), Rameshand Pugalendi (2005, 2006), Singh et al. (2010)

cancersis inducerria (Serratia

Barthomeuf et al. (2008), Iranshahi et al.(2007), Iranshahi et al. (2009a,b, 2008, 2004)


4.1. Bioactive compounds

Most of the bioactive compounds reported from asafoetida,belong to the sesquiterpene coumarins class. Umbelliprenin isthe rst splant Ferulaities thatcancer chetosis induc2008), 5-lipinammatoof Serratiasesquiterpehydroxyum10-R-acetoxferol, etc. Fsesquiterpeit should bnot exclusivparticularlybiological aorigins.

5. Discussi

Althougferent soursource of alarly easterrest of the wbeen used ihas been uMalaysia, N

New phditional usand antibacsome traditexample,mbeen reveaponents ofactivity (IClipoxygenasthis offersin the treaasafoetida acolleagues.

Anotherrmed by a(Saleem etnisms seemactivity of sby umbelliendogenoustudy, it hastion dependindicated tmental muUmbelliprechemoprevIn an in vivoity of umbeassay ofmoand 12-O-tWe found thrable with c

(Iranshahi et al., 2009b). Blocking the enzyme 5-lipoxygenase maybe plausiblemechanism accounting for at least part of the observedchemopreventive activity of umbelliprenin. It seems that umbel-liprenin might be a lead compound to design and synthesize new

tivesent iactivasafosed, 2, 3ble 2plituntedncluter-ial anto e

y whies.ihelmepor, Chinnal pis noer tharran009,rinsterpeferol.32adines maevelmmothesdivi

exmin c

ce oftreatoulds, caoetidtida.inclunentdatetidathe aproof a

l triastrorevi

tidant mies occomtida a

wled

wour theesquiterpene coumarin that is synthesized by theassa-foetida. There are a number of biological activ-

have been reported for this compound, includingmoprevention (Iranshahi et al., 2008, 2009b), apop-tion in a melanoma cell line (Barthomeuf et al.,oxygenase inhibition (Iranshahi et al., 2009a), anti-ry action (Iranshahi et al., 2009a) and depigmentationmarcescens (Iranshahi et al., 2004). Other bioactivene coumarins include galbanic acid, 8-acetoxy-5-S-belliprenin, farnesiferol A, farnesiferol B, farnesiferol C,y-11-hydroxyumbelliprenin, 10-R-karatavicinol, con-or simplicity, biological activities of the mentionedne coumarins are summarized in Table 3. However,e pointed out that these sesquiterpene coumarins aree to asafoetida. The compounds occur in other plants,in other Ferula species. For this reason, some of thesectivities have been reported for plants with different

on and conclusion

h asafoetida has been reported to be obtained from dif-ces, Ferula assa-foetida is considered to be the mainsafoetida. This plant is native to central Asia, particu-n Iran and Afghanistan, from where it is exported to theorld. Although asafoetida is not native to India, it has

n Indian medicine and cookery for ages. In addition, itsed in traditional medicine of other countries such asepal and Fiji.armacological studies have almost conrmed the tra-es of asafoetida as an antihelminthic, antispasmodicterial agent. In addition, there is a correlation betweenional uses of asafoetida and those of new studies. Forodernphytochemical andpharmacological studieshaveled that umbelliprenin (1) is one of the major com-asafoetida possessing strong lipoxygenase inhibitory50 =0.0725M) (Iranshahi et al., 2009a). Regardinges inhibition as one of approaches to treat asthma,a rationalization for the traditional use of asafoetidatment of asthma. Currently, anti-asthma activity ofnd umbelliprenin is investigated by the author and his

biological activity of asafoetida, which has been con-number of new studies, is cancer chemoprevention

al., 2001; Mallikarjuna et al., 2003). Different mecha-to impact on this activity such as radical scavengingulfur-containing compounds, lipoxygenase inhibition

prenin and its derivatives, increase in the activity ofs antioxidantsanddecrease inoxidativeparameters. Inabeenshownthat asafoetida inhibitsmicrosomal activa-ent mutagenicity of 2-acetamidoourene. The results

hat asafoetida may ameliorate the effect of environ-tagens especially present in the food (Kochhar, 2008).nin has also been shown to have remarkable cancerention in vitro and in vivo (Iranshahi et al., 2008, 2009b).study, we assessed the cancer chemopreventive activ-lliprenin in vivo by using a two-stage carcinogenesisuse skin tumors induced by peroxynitrite as an initiatoretradecanoylphorbol-13-acetate (TPA) as a promoter.at cancer chemopreventionof umbelliprenin is compa-urcumin, a well-known cancer chemopreventive agent

derivaRec

modicuse ofet al. utions 1see Taage ambe poisarily iThe wapotenta needactivitcountr

Antically rIn IranintestiThereHowevthat w

In 2coumasesquifarnesiIC50 =0amantpounddrug dand coture ofthan incompltigatedevidenin the

It shsurveyof asafasafoetainlycompo

Toasafoestudysafetystudiesclinica

It isin thisasafoediffereactivitof unaasafoe

Ackno

WeAsili fowith higher potency and more safety.n vivo study (Fatehi et al., 2004) has shown an antispas-ity that provides convincing support for the traditionaletida as an antispasmodic agent. In the study, Fatehia water extract of oleo-gum-resin at the concentra-, 5 and 7mg/ml on guinea-pig ileum (for more details). They observed a signicant reduction in the aver-de of the spontaneous contractions. However, it shouldout that a water extract of asafoetida does not neces-de all active components of the whole oleo-gum-resin.insoluble fraction of this oleo-gum-resin may also havetispasmodic components. Therefore, it seems there isvaluate the whole oleo-gum-resin for antispasmodicich is emphasized in traditional medicines of different

inthic property (or anthelmintic) is another emphat-ted traditional use of asafoetida in different countries.a and Nepal, it is traditionally used for infestation witharasites (Zargari, 1996; Ross, 2005; Emami et al., 2010).study regarding this important activity of asafoetida.e evaluation of its antihelminthic activity is somethingts further investigation.Lee et al. evaluated antiviral activity of sesquiterpenefrom asafoetida against inuenza H1N1. Among testedne coumarins, galbanic acid (12, IC50 =0.26g/ml),C (11, IC50 =0.29g/ml) and epi-conferdione (29,g/ml) exhibited the best potency, comparable to(IC50 =0.92g/ml) as anantiviral standard. These com-y also serve as promising lead compounds for newopment against viral infections, particularly inuenzan cold (Lee et al., 2009). Asafoetida is a complex mix-e compounds and may exert more pronounced effectsdual compounds. The antiviral activity of asafoetida, aixtureof variousantiviral compounds, needs tobe inves-linical trials or in vivo studies. However, the aforesaidfer a rationalization for the traditional uses of asafoetidament of upper respiratory diseases.be pointed out, however, a number of pharmacological

rried out on asafoetida (Table 2), used a water extracta that is not the most common application form ofAs mentioned above, the aqueous extract does not cer-de non-polar components or even some of the actives of the whole oleo-gum-resin., one study has only addressed potential toxicity ofin a case report (Kelly et al., 1984). There is a need tocute toxicity, sub acute toxicity, chronic toxicity andling of asafoetida. However, detailed animal toxicitysafoetida and their compounds are required prior tols.ngly believed that detailed information as presentedew on the phytochemical and biological activities ofprovides detailed evidence for the use of this plant inedicines. Regarding the rich background of biologicalf asafoetida, it seems there are still a large numberplished investigations, particularly clinical trials ofnd its bioactive compounds.

gments

ld like to thank Dr. Seyyed Ahmad Emami and Dr. Javadir scientic consulting and kind help.


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Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin)A reviewIntroductionTraditional usesPhytochemistryCoumarins and sesquiterpene coumarinsSulfur-containing compoundsOther compounds

PharmacologyBioactive compounds

Discussion and conclusionAcknowledgmentsReferences

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Asafoetida