Review Article Pharmacology and Phytochemistry of Oleo …downloads.hindawi.com/journals/scientifica/2015/138039.pdfReview Article Pharmacology and Phytochemistry of Oleo-Gum Resin

Review ArticlePharmacology and Phytochemistry of Oleo-Gum Resin ofCommiphora wightii (Guggulu)

Prerna Sarup Suman Bala and Sunil Kamboj

MM College of Pharmacy Maharishi Markandeshwar University Mullana Ambala Haryana 132 037 India

Correspondence should be addressed to Prerna Sarup psarup puhotmailcom

Received 18 June 2015 Revised 28 August 2015 Accepted 7 September 2015

Academic Editor Marie-Aleth Lacaille-Dubois

Copyright copy 2015 Prerna Sarup et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Guggulu is an oleo-gum resin which exudes out as a result of injury from the bark of Commiphora wightii (Arnott) Bhandari[syn Commiphoramukul (Hook Ex Stocks) EnglBalsamodendronmukul (Hook Ex Stocks) Family Burseraceae] It has been usedin the Ayurveda since time immemorial for the treatment of variety of disorders such as inflammation gout rheumatism obesityand disorders of lipids metabolism It is a mixture of phytoconstituents like volatile oil which contains terpenoidal constituentssuch as monoterpenoids sesquiterpenoids diterpenoids and triterpenoids steroids flavonoids guggultetrols lignans sugars andamino acidsThis review is an effort to compile all the information available on all of its chemical constituents which are responsiblefor its therapeutic potentialThewild occurrence of this species is restrictedmainly to the dry regions of Rajasthan andGujarat Statesof India and the bordering regions of Pakistan Oleo-gum resin guggulu tapped from the stems of this species is consumed inhigh volumes by the Indian herbal industriesThere has been a decline in its wild population over the last several decades as a resultof habitat loss and degradation coupled with unregulated harvesting and tapping of oleo-gum resin This species is consequentlyassessed as Critically Endangered and enlisted in the IUCN red list of threatened species

1 Introduction

Guggulu consists of oleo-gum resin obtained as an exudatefrom the tapping of stem and branches of Commiphorawightii (Arnott) Bhandari [syn Commiphora mukul (HookEx Stocks) Engl Balsamodendron mukul (Hook Ex Stocks)Family Burseraceae] The plant is commonly known asguggul tree and is found in arid areas of India Bangladeshand Pakistan In India it is found in Rajasthan GujaratAssam Madhya Pradesh and Karnataka It is a small bushytreewith thorny branches and produces a yellowish gum resin(guggulu) in small ducts located throughout its bark Thetrees are tapped bymaking an incision on the barkThe resinwhich flows out is allowed to harden before it is collectedThe tree is tapped fromNovember to January and the resin iscollected through May to June A guggul tree yields between250 to 500 g of dry resin during each collection season [1 2]

In Indian traditional system of medicine guggulu hasbeen used for thousands of years in the treatment of arthritisinflammation gout rheumatism obesity and disorders oflipids metabolism [3] It is known by different names likeguggula guggul guggal gugar and Indian bdellium [4]

Guggulu occurs in vermicular pieces of pale yellowor brown coloured mass with aromatic odour and bitterastringent taste when fresh it is viscid and golden colouredIt should produce not more than 5 percent of total ash and 1percent of acid-insoluble ash It yields not less than 27 percentof alcohol-soluble matter and not less than 53 percent ofwater-solublematterThegenuine samples of guggulu contain1 percent of volatile oil [2] and between 10 and 15 percent ofguggulsterones (119885 and 119864) [3]

Guggulu Shodhana (shodhan vidhi) It has been mentioned inAyurvedic texts that administration of raw guggulu may leadto skin rashes irregular menstruation diarrhoea headachemild nausea and with very high doses liver toxicity [5]In order to overcome unwanted effects of raw gugguluAyurveda describes a number of purification processes(shodhan vidhi) using different fluids (dravyas) which notonly take care of the adverse effects but also enhance thetherapeutic activity According to Ayurvedic texts guggulumust be purified before incorporating into formulations [1]During a process of shodhan guggulu is treated with specificmaterials of biological origin for example herbal juices cow

Hindawi Publishing CorporationScientificaVolume 2015 Article ID 138039 14 pageshttpdxdoiorg1011552015138039

2 Scientifica

(1) 120572-Camphorene (2) Cembrene-A

Figure 1

urine and cowmilk It is possible that some of the properties(chemical and biological) of shodhan materials are added toguggulu during the purification process It is also possible thatsome of the toxic or harmful constituents of raw guggulu areneutralized detoxified or removed during this process

There are a large number of commercial polyherbal anti-inflammatory formulations which are using guggulu as thechief ingredient [6] However no study has been done toinvestigate the process of Ayurvedic purification and itsprobable effect on therapeutic efficacy except for one reportwhich states that gastric irritancy of guggulu is reduced withpurification [7]

During the process of purification foreign matter isremoved from raw guggulu manually and is then brokeninto small pieces The broken mass is wrapped in a piece ofcloth (called potli) and hanged into an inert container (calleddola yantra) containing one of the recommended mediawhich are gomutra (cow urine) triphala kasaya (decoctionof triphala) vasapatra kasaya (decoction of Adhatoda vasicaleaves) vasapatra savrasa (aqueous extract ofAdhatoda vasicaleaves) dugdha (milk) and water The guggulu is keptimmersed while fluid is boiled till all the soluble matter ofguggulu is dissolved in the purifying vehicle The insolublepart of guggulu is taken out and discarded Further boiling iscontinued till guggulu solution forms a soft mass It is thenpoured out over a smooth wooden board smeared with cowghee or castor oil anddried in the sunThedriedmass is calledpurified guggulu (suddh guggulu) [1]

2 Phytoconstituents of Guggulu

Guggulu contains diterpenoids triterpenoids steroids long-chain aliphatic tetrols aliphatic esters ferulates lignanscarbohydrates and a variety of inorganic ions besides minoramounts of sesamin and other unidentified constituents

21 Volatile Oil and Its Terpenoidal Constituents

211 Monoterpenoids The gum resin of C wightii yieldsabout 04 of essential oil by steam distillation and its chiefcomponents are myrcene dimyrcene and polymyrcene [8]Other components of the oil are eugenol d-limonene 120572-pinene (plusmn) linalool cineole 120572-terpineol d-120572-phellandrenemethylheptanone bornyl acetate (plusmn) geraniol and someother unidentified compounds [9]

OH

(3) Cembrene (4) Mukulol

Figure 2

212 Sesquiterpenoids The gum resin of C wightii has beenreported to contain bicyclic sesquiterpene cadinene [9]

213 Diterpenoids Diterpenoid constituents from gugguluinclude 120572-camphorene (1) (Figure 1) [10] cembrene-A (2)(Figure 1) cembrene (3) (Figure 2) [10] and other cem-brenoids Cembrene-A is one of themost elementary tetraen-es derived from geranylgeranyl pyrophosphate by C-1 to C-14cyclization

Mukulol (allylcembrol) (4) (Figure 2) is a new cembranealcohol which was isolated from the aerial parts and alsofrom the resin of guggulu [11 12] The allylcembrol structurewas established by spectral analysis and mild dehydrationwhich yielded cembrene Other isolated cembrane typediterpenes include isocembrol (5) (Figure 3) and 4-epiisocembrol (6) (Figure 3) (1119864 4119864 8119864)-4814-Trimethyl-11-(1-methylethyl)4-methoxycyclotertradeca-148-triene (7)(Figure 3) (2119864 12119864)-2713-trimethyl-9-(1-methylethyl)-15-oxabicyclo [1210] pentadeca-212-diene-7-ol (8) (Figure 4)and (4119885 6119864)-47121515-pentamethylbicylco [931] pentade-ca-46-diene-12-ol (9) (Figure 4) were novel compoundsobtained by bioassay-guided isolation from hexane-solubleportion of the methanol extract of guggulu [13]

214 Triterpenoids Polypodane-type triperpenes myrrhan-ol A (10) (Figure 5) B (11) (Figure 5) and C (12) (Figure 5)myrrhanone A (13) (Figure 6) myrrhanone B (14) (Figure 6)[14 15] myrrhanone A acetate (15) (Figure 6) commipherol(16) (Figure 7) commipherin (17) (Figure 7) and octanor-dammarane triperpenoid epimansumbinol (18) (Figure 8)

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OMe

(7) (1E4E8E)-4814-Trimethyl-11-(1-methylethyl)-(5) Isocembrol OH 4-methoxycyclotertradeca-148-triene(6) 4-Epiisocembrol OH

R1

R1

R2

R2

CH3

CH3

Figure 3

O

OH

HO

(8) (2E12E)-2713-Trimethyl-9-(1-methylethyl)- (9) (4Z6E)-47121515-Pentamethylbicylco15-oxabicyclo [1210] pentadeca 212-diene-7-ol [931] pentadeca-46-diene-12-ol

Figure 4

R

(10) Myrrhanol A(11) Myrrhanol B COOH(12) Myrrhanol C

R

OH

HO

CH3

CH2OH

Figure 5

have been isolated from the gum resin [16] The isolationof two more triterpenoidal components has been reportedwhich are identified as mansumbinone (19) (Figure 9) andmansumbinoic acid (20) (Figure 9) [17]

The absolute stereostructure of myrrhanol A was deter-mined to be (3119878 5119878 8119877 9119877 10119878)-3830-trihydroxypolypo-da-13119864 17119864 21119864-triene Myrrhanol B is 30-oic acid ofmyrrhanol A with altered stereostructure at C-5 (5119877 incontrast to 5119878 in myrrhanol A) Myrrhanone A and B are3-keto analogue of myrrhanol A and B respectively [15]

R

O

R

(13) Myrrhanone A

(14) Myrrhanone B COOH

(15) Myrrhanone A acetate

OH

CH2OH

CH2OAc

Figure 6

A myrrhanone derivative (13119864 17119864 21119864)-8-hydroxypolyp-oda-131721-trien-3-one (21) (Figure 10) and a myrrhanolderivative (13119864 17119864 21119864)-polypoda-131721-trien-318-diol(22) (Figure 10) have also been isolated [13]

22 Steroids Isolation of several steroidal constituents hasbeen reported from the gum resin The major constituentsinclude E-guggulsterone (23) (Figure 11) Z-guggulsterone(24) (Figure 11) guggulsterol-1 (25) (Figure 12) guggulsterol-II (26) (Figure 12) guggulsterol-III (27) (Figure 12) [18]guggulsterol-IV (28) (Figure 13) guggulsterol-V (29)(Figure 13) [19] and guggulsterol-VI (30) (Figure 13) [20]

4 Scientifica

R

OH

OH

R(16) Commipherol(17) Commipherin COOH

CH2OH

Figure 7

HO

(18) Epimansumbinol

Figure 8

Other isolated steroids are 20120572-hydroxy-4-pregnen-3-one(31) (Figure 13) 20120573-hydroxy-4-pregnen-3-one and 16120573-hydroxy-417(20)-Z-pregnadien-3-one which has beendesignated as Z-guggulsterol [20] Progesterone and relatedsteroids 4-pregnene-316-dione (32) (Figure 13) (20R)-20-acetoxy-4-pregnene-316-dione16120573-acetyloxypregn-417(20)-trans-diene-3-one (33) (Figure 14) 3120572-acetyloxy-5120572-pregnan-16-one (34) (Figure 14) and 20R22R-dihydrox-ycholest-4-en-3-one (35) (Figure 14) have also been isolated[16] Cholesterol has also been reported Three new andrecently isolated steroids are guggulsterone-M dihydroguggulsterone-M (36) (Figure 14) and guggulsterol-Y (37)(Figure 14) [17] The steroidal constituents have been relatedwith hypolipidemic and anti-inflammatory activities of thedrug [13]

23 Flavonoids An ethanolic extract of trunk of C wightiiwas separated on column packed with silica gel to give a newantifungal flavone named muscanone (38) (Figure 15) alongwith known naringenin Muscanone was found to be activeagainst Candida albicans in microbial sensitive assay [21]

The major flavonoid components of the flowers ofC mukul were identified as quercetin (39) (Figure 16)quercetin-3-O-120572-L-arabinose (40) (Figure 17) quercetin-3-O-120573-D-glucuronide (41) (Figure 17) quercetin-3-O-120573-D-galactoside (42) (Figure 17) quercetin-3-O-120572-L-rhamnoside(43) (Figure 17) and pelargonidin-35di-O-glucoside (44)(Figure 17) [22]

24 Guggultetrols A crystalline material was isolated fromthe saponified gum resin which was characterized as a mix-ture of octadecan-1234-tetrol (45) (Figure 18) nonadecan-1234-tetrol (46) (Figure 18) and eicosan-1234-tetrol (47)

(Figure 18)withminor amount of other components possiblylower (C-16 and C-17) and higher (C-21 and C-22) homol-ogous tetrols These compounds constitute a new class ofnaturally occurring lipids guggultetrols They are long-chainlinear aliphatic tetrols with hydroxyl functions at C-1 C-2 C-3 and C-4 positions Through derivatization and preparativeGLC guggultetrol-18 (48) (Figure 18) and guggultetrol-20(49) (Figure 18) were obtained in pure form [23]

A mixture of two ferulates (119899 = 16 17) (50) (Figure 19)with an unusual skeleton was found to be responsible for thecytotoxic action of the drug They have been isolated fromcytotoxic fraction of ethyl acetate extract of guggulu It wasidentified as a mixture of esters based on homologous long-chain tetrols and acid [24]

25 Lignans Two lignans sesamin [18] and diayangambin(51) (Figure 20) [25] have been reported from gugguluAlso 551015840-tetrahydro-11198673119867-furo[34-c]furan-14-diylbis[7-(methoxy)-13-benzodioxole] (52) (Figure 20) has beenreported from methanolic extract of guggulu [13]

26 Sugars Complete hydrolysis of gum part of resinyielded L-arabinose D-galactose L-fructose (traces) and4-O-methyl-D-glucuronic acid Graded hydrolysis of thegum furnished an aldobiouronic acid [6-O-(4-O-methyl-120573-D-glucopyranosyluronic acid)-D-galactose] [26] Hydroly-sis of methylated gum furnished 2346-tetra-O-methyl-D-galactose 23-di-O-methyl-L-arabinose 234-tri-O-methyl-D-galactose 24-di-O-methyl-D-galactose and 234-tri-O-methyl-D-glucuronic acid in the ratio of 1 1 1 2 1 Theprovisional structure showed the gum to be a highly branchedpolysaccharide containing 1ndash6 1ndash3 and 1ndash5 type of linkage[27]

27 Amino Acids C mukul was extracted with alcohol andthe extract after removal of the solvent was partitionedbetween water and ether The aqueous fraction was chro-matographed and it showed the presence of various aminoacidsThe amino acids detectedwere cystine histidine lysinearginine aspartic acid serine glutamic acid threoninealanine proline tyrosine tryptophan valine leucine andisoleucine [28]

3 Traditional Uses of Guggulu

Guggulu has a long history of use in Ayurveda The Athar-vaveda is the earliest reference containing its medicinal andtherapeutic properties [29] Detailed description regardingits actions uses and indications and the varieties of guggulhave been described in numerous Ayurvedic treatises includ-ing Charaka Samhita (1000 BC) Sushruta Samhita (600BC) and Vagbhata (7th century AD) In addition variousmedical lesions were written between the 12th and 14thcenturies AD [30] Guggulu has been used to treat obesityosteoarthritis rheumatoid arthritis gout facial paralysissciatica constipation haemorrhoids liver disorders inflam-mation cyst cervical lymphadenitis coronary thrombosisanaemia diabetes urinary calculus increased frequency andturbidity of urine and skin diseases [31 32]

Scientifica 5

HO

H

H

H

HOOC

H

(19) Mansumbinone (20) Mansumbinoic acid

Figure 9

RH

OH

R(21) (13E17E21E)-8-Hydroxypolypoda-131721-trien-3-one =O(22) (13E17E21E)-Polypoda-131721-trien-318-diol OH

Figure 10

O

O

(24) Z-Guggulsterone H

HR1

R1

R2

R2

CH3

(23) E-Guggulsterone CH 3

Figure 11

It has a wide range of usefulness in indigenous medicineIt is astringent and antiseptic and acts as a bitter stomachicand carminative when taken internally Like all oleo resinsit causes increase in number of leucocytes and stimulatesphagocytosis It acts as a diaphoretic expectorant diureticuterine stimulant and emmenagogue The resin is usedin the form of lotion for indolent ulcers and as a garglein caries spongy gums pyorrhea chronic tonsillitis andulcerated throat Inhalation of the fumes from burnt gugguluis recommended in hay fever acute and chronic nasal catarrhchronic laryngitis chronic bronchitis and phthisis It is aningredient of ointment for ulcers [2]

O

H

OH

(25) Guggulsterol-I OH OH(26) Guggulsterol-III OH H(27) 20R22R-Dihydroxycholest-4-en-3-one H OH

R1

R1

R2

R2

Figure 12

4 Pharmacological Activity of Guggulu

41 Hypolipidemic Activity The lipid lowering effect of gug-gulu with special reference to atherosclerosis and obesity(medoraga) was first reported in a doctorate thesis submittedto the Banaras Hindu University (BHU) in January 1966Earlier to this work guggulu was well known as an Ayurvedicdrug for the treatment of various types of arthritis Thiswork was inspired by a rather obscure shloka in Sanskritin the well-known Ayurvedic treatise Sushruta Samhita Theshloka deals in an extraordinarily lucid and scientificmannerwith the etiology pathogenesis and treatment of obesityand associated lipid disorders and their complications The

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HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH

(28) Guggulsterone-II (29) Guggulsterone-IV

HO

OAc

O

H

(30) Guggulsterone-V (31) Guggulsterone-VI

OH

H

O

(32) Z-Guggulsterol

Figure 13

hypolipidemic activity was shown in animals as well as inpatients of obesity and hypercholesterolemia [33]

In carefully planned studies carried out (over a period oftwo years) on rabbits in which hyperlipidemia was inducedby feeding cholesterol (in hydrogenated vegetable oil) itwas demonstrated for the very first time that crude guggulucould not only lower significantly the serum cholesterol inhypercholesterolemic rabbits but also protected these animalsagainst cholesterol-induced atherosclerosis at the fatty streakstage It also reduced the body weight of the animals Asimilar trend to reduce significantly the serum cholesterollevels in patients with obesity and hypercholesterolemia wasfound in clinical studies with crude guggulu The CentralDrug Research Institute (CDRI) Lucknow has been engagedin chemical pharmacological and clinical studies on guggulu[33]

Gugulipid an ethyl acetate extract of the oleoresinstandardized at CDRI has been marketed in India since 1988

as a hypolipidemic agent It contains 119885-guggulsterones and119864-guggulsterones which are purported to be the compoundsresponsible for the hypolipidemic activity of the guggulu [3435] Gugulipid contains not less than 4 percent and not morethan 6 percent of guggulsterones (119885and 119864) The decision touse the ethyl acetate extract rather than two guggulsteroneswas primarily for commercial reasons and was also becauseof the fact that other components of the ethyl acetate extractshowed synergistic (hypolipidemic) effect [33] A number ofclinical studies were carried out to confirm hypolipidemicactivity of guggulu and gugulipid [36 37] The findings ofmulticentric clinical trials carried out with gugulipid at sevendifferent centres in India coordinated in collaboration withCDRI confirmed the role of gugulipid as a hypolipidemicagent [36]

The hypolipidemic activity of guggulu and its variousfractions has been studied in several animal models andclinical studies [1] Initial studies reported that crude guggulu

Scientifica 7

O

H

O

O

OAc

(33) 4-Pregnene-316-dione (34) 16120573-Acetyloxy-pregn-417(20)-trans-dien-3-one

O

H

(35) 3120572-Acetyloxy-5120572-pregnan-16-one

O

O

(36) Dehydroguggulsterone-M (37) Guggulsterol-Y

HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15

has encouraging hypolipidemic activity in rabbits [38] Thisactivity was also confirmed in other animals including whiteleghorn chicks domestic pig Presbytis monkey and albinorat [1]

Studies were also conducted on the petroleum etherfraction (A) alkali washed neutral portion (B) and petrol-insoluble fraction (C) in healthy 8-week-old male white

leghorn chicks in which hypercholesterolemia was inducedby atherogenic diet fed for 2-3 weeks All the fractionswere found to lower the serum cholesterol with fractionA being the most potent and fraction B being the leastpotent None of the three fractions however was found toprevent the induction hypercholesterolemia in the chicks[38]

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O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16

Further studies on the alcoholic extract and two purecompounds (a terpenoid and a steroid) isolated from thepetroleum ether extract showed that the steroid was highlypotent in lowering the serum cholesterol by 693 percentThealcoholic extract could lower the cholesterol by 592 percentwhereas the terpenoid lowered it by 543 percent [38]

In another study highly significant reduction in levelsof mean serum cholesterol and triglyceride was observed ingroups of animals receiving high-fat diet for onemonth alongwith guggulu which clearly demonstrated its hypolipidemicactivity Additionally administration of guggulu partiallyreversed the atherosclerosis in the aorta that was induced byhigh-fat diet [39]

Clinical studies on C mukul showed its hypolipidemiceffect and the outcome of change in lipid profile upon itsadministration This study showed significant decrease intotal cholesterol and LDL cholesterol after treatment withguggulu [40]

The hypolipidemic activity of the isomers 119864-guggulstero-ne and119885-guggulsterone has also been studied in animalmod-els Administration of guggulsterone (119885 and 119864) significantlylowered serum lipid levels of rats with either triton (WR-1339)or cholesterol-induced hyperlipidemia [41]

Several mechanisms of action have been proposed forthe hypolipidemic action of guggulu Guggulu may decreasehepatic steroid production which ultimately increases thecatabolism of plasma LDL cholesterol Alternatively theproposed active components of guggulu guggulsterones 119864and119885 may increase hepatic binding sites for LDL cholesterolthus increasing LDL clearance However recent findings havesuggested that guggulsterone 119864 and 119885 are highly efficaciousantagonist of the farnesoid X receptor (FXR) a nuclearhormone receptor that is activated by bile acids thus allowingincreased cholesterol catabolism and excretion from the body[42 43]

Guggulsterone and cembrenoids from C mukul stembark resin were shown to be specific modulators of twoindependent sites that are also modulated by bile salts to con-trol cholesterol absorption and catabolism Guggulsteroneantagonized the chenodeoxycholic acid-activated nuclearfarnesoid X receptor (FXR) which regulates cholesterolmetabolism in the liver The cembrenoids did not show anoticeable effect on FXR but lowered the cholate-activated

rate of human pancreatic IB phospholipase A2(hPLA2)

which controls gastrointestinal absorption of fat and choles-terol [44]

42 Effect on Platelet Aggregation and Fibrinolytic ActivityThe purified steroid mixture from guggulu completely inhib-ited ADP adrenaline or serotonin induced platelet aggrega-tion No difference was observed between the effectivenessof the steroid mixture and the purified guggulsterone 119864 or119885 The effect of guggulsterones 119864 and 119885 was very similar tothe inhibitory effect of clofibrateThis finding has therapeuticvalue in myocardial infarction and thromboembolism [45]

The effect of guggulu on fibrinolysis and platelet adhe-siveness in coronary heart disease was studied Guggulufraction A (pet ether extract) in daily dose of 1 g wasadministered to healthy individuals (group I) and to patientsof coronary artery disease (CAD) (group II) for a period of 30days Serum fibrinolytic activity increased while the plateletadhesive index decreased which was statistically significantin healthy individuals and in CAD patients In view of thisguggulu fraction A may be a useful therapeutic agent in themanagement of coronary artery disease [46]

43 Thyroid Stimulatory Activity Administration of ethano-lic extract of guggulu to the female albino mice for 15 daysenhanced the triiodothyonine (T3) concentration and T3T4ratio while nomarked change in the concentrations of serumthyroxine (T4) was observed [47] 119885-Guggulsterone wasshown to be responsible for the thyroid stimulatory action ofguggulu Administration of isolated 119885-guggulsterone to ratsled to significant increase in all thyroid function parametersnamely uptake of iodine by the thyroid enzymes involved inthe synthesis of thyroid hormones and tissue oxygen uptakethus suggesting thyroid stimulatory action [48]

44 Anti-Inflammatory and Antiarthritic Activity Theresults of several studies confirm anti-inflammatory andantiarthritic activities of guggulu [13 15 25 49ndash52] The 50percent aqueous methanolic extract was found to exhibitan anti-inflammatory effect on adjuvant-induced air pouchgranuloma in mice The methanolic extract inhibited nitricoxide production in lipopolysaccharide activated mouseperitoneal macrophages [15] A crystalline steroid wasisolated from the petroleum ether extract and tested in ratsfor inhibition of inflammation induced by Freundrsquos adjuvantIt inhibited the full development of the primary lesions inadjuvant arthritis and also reduced the severity of secondarylesions as compared with the untreated control group [53]

Guggulosomes prepared using guggul with ibuprofenby bath sonication and trituration methods were studiedfor anti-inflammatory activity It was clearly shown thatguggulosomes had more efficacy than ibuprofen and bothguggul and ibuprofen had synergistic effectThe study provedthat guggul could serve as a carrier for entrapping drugs andfor their sustained release action [54]

Several animal studies have demonstrated the effective-ness of guggulu extract in standard osteoarthritis (OA)models The authors had conducted both animal and clinicalinvestigations of guggulu for OA prior to this study The goal

Scientifica 9

O

O

O

O

R

O

O

O

O

R(40) Quercetin-3-O-120572-L-arabinose H

(43) Quercetin-3-O-120572-L-rhamnoside

(41) Quercetin-3-O-120573-D-glucuronide COOH

(42) Quercetin-3-O-120573-D-galactoside

HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O

(44) Pelargonidin-35di-O-glucoside

HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H

(45) Octadecan-1234-tetrol (48) Guggultetrol 18 (46) Nonadecan-1234-tetrol (49) Guggultetrol 20(47) Eicosan-1234-tetrol n = 15

n = 14

n = 13

CH2OHCH3(CH2)n CH CH CH

OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18

of this study was to determine the effectiveness of guggulufor reduction of pain stiffness and other symptoms that arisefrom OA [55]

45 Antioxidant Activity The antioxidant property of gug-gulu helped stop the oxidation of cholesterol and subsequenthardening of the arteries reduced the stickiness of plateletand also lowered the risk of coronary artery disease [45] Italso enhanced the production of thyroxin and triiodothyro-nine these hormones increase the metabolism of carbohy-drates and protein synthesis and help in lowering the lipidactivity [47]

The antioxidant activity was attributed to the presence ofguggulsterones It was tested in vitro against the formation ofoxygen free radicals The oxidation of human LDL inducedby Fe2+ or by rat peritoneal macrophages caused markedformation of lipid peroxidation products Guggulsterone(50 120583M) prevented the generation of thiobarbituric acidreactive substances and lipid hydroperoxide of low densitylipoprotein in above systemHowever it did not protect lipidsagainst the formation of conjugated dienes the initial stepof lipid peroxidation cascade Guggulsterone significantlyinhibited the reaction of lipid peroxidation in liver micro-somes challenged with Fe2+ and sodium ascorbate Thus

10 Scientifica

COO

(50) Guggultetrol ferulate

OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3

(52) 55998400-Tetrahydro-1H3H-furo[34-c]furan-14-diylbis[7-(methoxy)-

Figure 20

the protective action of guggulsterone might also be due tofree radical scavenging propertyThemetal chelating capacityof guggulsterone might be contributing to its antioxidantactivity [56] Also the alcoholic extract ofC mukul exhibitedantioxidant property [57]

46 Antiatherosclerotic Activity LDL has been found toaccumulate in atherosclerotic lesions and is the major sourceof the cholesterol accumulation in human foam cellsThere isevidence that LDL oxidation is essential for atherogenesis andthe antioxidants that prevent this oxidation may either slowdown or prevent atherogenesis Guggulsterones the lipid-lowering components of guggulu effectively inhibited invitro LDL oxidation (as discussed under antioxidant action)

Thus the combination of antioxidant and lipid-loweringproperties of guggulu makes it especially beneficial againstatherogenesis [58]

47 Cardioprotective Activity Guggulsterones are shown tobe effective cardioprotectives Myocardial necrosis inducedby isoproterenol in rats caused marked increase in serumcreatine phosphokinase and glutamate pyruvate transami-nase Phospholipase xanthine oxidase and lipid peroxideswere simultaneously enhanced in ischemic heart followingdepletion of glycogen phospholipids and cholesterol Treat-ment with guggulsterone at a dose of 50mgkg significantlyprotected cardiac damage as assessed by the reversal of bloodand heart biochemical parameters in ischemic rats [59]

48 Cytotoxic Activity Ferulates important bioactive con-stituents identified from the guggulu gum were reportedto play a significant role in in vitro cytotoxicity by decreas-ing the cell viability in MCF-7 (breast) tumor cells PC-3(prostate) tumor cells and parental and transfected P 388cells [49] Therefore ferulate compounds are used in themethod for prevention and treatment of abnormal cell growthand proliferation of inflammation neoplasia and cardio-vascular disease Ethyl acetate extract showed significant invitro cytotoxicity A fraction showing cytotoxic activity wascharacterized as a mixture of two ferulates with an unusualskeleton by spectral and chemical methodsThis fraction alsoshowed moderate scavenging effect against 22-diphenyl-1-picryl hydrazyl (DPPH) radicals [60]

Treatment with gugulipid significantly inhibited the via-bility of human prostate cancer cell line LNCaP (androgen-dependent) and its androgen-independent variant (C-81)with IC

50of 1120583M(24 h treatment) thus indicating its possible

role in apoptosis and cancer prevention [60] The results ofthis study indicated that guggulsterone inhibited prolifera-tion of PC-3 cells in culture by causing apoptosis whereasa normal prostate epithelial cell line is resistant to growthinhibition and apoptosis induction by this phytoconstituentThese observations provided rationale for further preclinicaland clinical evaluation of guggulsterone for its efficacy againstprostate cancer [61]

49 Antifertility Activity Guggulu administered orally (2 and20mg100 g body weight) to female rats decreased the weightof the uterus ovaries and cervix whereas glycogen and sialicacid levels in these organs increased This suggested thatguggulu may be useful as an antifertility agent [62]

410 Skin Diseases Administration of gugulipid was report-ed to be effective in the treatment of nodulocystic acne Astudy in 21 patients found that gugulipid was as effectiveas tetracycline in the treatment The patients with oily facesresponded better to the gugulipid treatment [63]

411 Antihyperglycemic Activity Administration of alcoholicextract of C mukul at a dose of 200mgkg for 60 continuousdays reduced plasma glucose levels in streptozotocin-induceddiabetic rats [57] A study showing effect of guggulsterone

Scientifica 11

isolated from C mukul in high-fat diet induced diabetic ratshas also been reported Different biochemical parameters likeGTT glycogen content glucose homeostatic enzymes (likeglucose-6-phosphatase and hexokinase) insulin release invivo and expression profiles of various genes involved incarbohydrate and lipid metabolism clearly demonstrated thehypoglycemic effectThe results suggested that guggulsteronehas both hypoglycemic and hypolipidemic effects which canhelp cure type II diabetes [64]

412 Antimicrobial Activity The volatile oil of C mukul wasfound to be highly effective against Rhyzopertha dominicawhich suggested its role as a fumigant The ethanolic extractof C mukul exhibited best antibacterial activity at 5mgmL against multidrug-resistant Klebsiella pneumonia [65]An active compound 5(1-methyl1-aminoethyl)-5-methyl-2-octanone of the methanolic extract of guggulu gum pos-sessed significant antibacterial activity against Gram-positivebacteria and moderate activity against Gram-negative bacte-ria [66ndash68]

5 Safety and Toxicity

It has been mentioned in Ayurvedic texts that administrationof raw guggulu may sometimes lead to skin rashes irregularmenstruation diarrhoea headache mild nausea and withvery high doses liver toxicity [5] In order to overcome theside effects of raw guggulu Ayurveda describes a number ofpurification processes (shodhan vidhi) in different ldquodravyasrdquothat is fluids which not only take care of the adverseeffects but also enhance the therapeutic activity [2] It is alsomentioned in Ayurvedic texts that guggulu must be purifiedbefore incorporation into herbal formulations There are alarge number of commercial polyherbal anti-inflammatoryformulations which are using guggulu as the chief ingredient[52]

The clinical trials done with standardized gum guggulextracts reported transient side effects such as skin rashesdiarrhoea and irregular menstruations [33] A report alsostates that out of 22 individuals receiving 2160mg gugguludaily for 12 weeks 10 persons experienced one or anotherside effect including gastrointestinal distress fatigue andskin rash [69] Skin rashes have also been reported in othertrials using 1-2 g guggulipid (ethyl acetate fraction) daily for amonth This study did not report any intestinal distress [70]

Although generally accepted as relatively safe cautionmay be warranted during guggul consumption There is littleor no information on toxicity with the use of guggulu

6 Conclusions

From this review article it is concluded that the resin ofCommiphora wightii guggulu has emerged as a good sourceof the traditional medicines for the treatment of inflam-mation arthritis obesity microbial infection wound painfractures tumor and gastrointestinal diseases It is one of theoldest and the most prominent herbs in Ayurvedic medicineGuggulu is a versatile drug and because of its paranormalproperties it is very valuable in treating variety of disorders

Pharmacological results have validated the use of this plantin the traditional medicines This plant contains a num-ber of bioactive constituents including terpenoids steroidsflavonoids guggultetrols lignans sugars and amino acidsGuggulsterones 119864 and 119885 are the chief bioactive constituentsof this resin and are endowedwith immense pharmacologicalvalueThese conclusions could open a newwindowon the useof this plant inAyurvedaThis review clearly authenticates theSanskrit definition of the term ldquoguggulrdquo whichmeans one thatprotects against diseases It is superbly reflected and provedby the diverse medicinal uses of this Ayurvedic drug

In vitro studies and clinical trials help improve andadvance medical careThey also assist health care profession-als to direct resources to the strategies and treatments thatwould work best for a particular type of ailment Althoughthe use of guggulu in therapeutic doses appears to be safeand nontoxic more and more of such studies should still beconducted so that chances of any toxicity if any can be ruledout It has also been mentioned that during the course ofusing guggulu one should avoid foods that are sour or bitter intaste alcohol excessive exercise physical and mental strainanger and exposure to direct sunlight Such data can only bevalidated when we would choose in vitro studies over in vivostudies

Also this plant is listed in IUCN list and thus rationaleusage of the plant is the need of the hour so that we donot end up depleting this wonder drug of high therapeuticimportance Keeping this in view stem bark and leaf ofthis plant should receive more attention so that the completedepletion on account of plant death due to tapping can bechecked This plant still possesses an unexplored potentialand expansion of research materials would provide moreopportunities for the discovery of novel bioactive principlesfrom this plant

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

One of the authors Prerna Sarup gratefully acknowledgesthe University Grants Commission for the grant of RFSMSfellowship

References

[1] The Ayurvedic Pharmacopoeia of India (Formulations) Depart-ment of Indian Systems ofMedicine andHomeopathyMinistryofHealth and FamilyWelfare Government of India NewDelhiIndia 1st edition 2007

[2] The Ayurvedic Pharmacopoeia of India Department of IndianSystems of Medicine and Homeopathy Ministry of Health andFamily Welfare Government of India New Delhi India 1stedition 2001

[3] N L Urizar and D DMoore ldquoGugulipid a natural cholesterol-lowering agentrdquo Annual Review of Nutrition vol 23 pp 303ndash313 2003

12 Scientifica

[4] Indian Pharmacopoeia The Controller of Publications NewDelhi India 1996

[5] S A Masten Gum Guggul and Some of Its Steroidal Con-stituents Review of Toxicological Literature vol 2 US Depart-ment of Health and Human Services National ToxicologyProgram (NTP) National Institute of Environmental HealthSciences (NIEHS) National Institutes of Health Durham NCUSA 2005

[6] M Karan V Kumar V Suneja and K Vasisht ldquoCommercialherbal anti-inflammatory formulationsmdasha surveyrdquo Pharmacosvol 36 pp 14ndash25 2009

[7] V D Sangle S D Nadkarni M K Vahalia and M S DarpldquoThe study of effect of ayurvedic processing of Commiphorawightii on gastric irritancy index in experimental animalsrdquoIndian Drugs vol 41 no 5 pp 268ndash271 2004

[8] A Bhati ldquoEssential oil from the resin of Commiphora mukulHook Ex stocksrdquo Journal of the Indian Chemical Society vol27 pp 436ndash440 1950

[9] V K Saxena and R N Sharma ldquoConstituents of the essential oilfrom Commiphora mukul gum resinrdquo Journal of Medicinal andAromatic Plant Sciences vol 20 pp 55ndash56 1998

[10] G Rucker ldquoMonocyclic diterpenes from Indian gugul resin(Commiphoramukul)rdquoArchiv der Pharmazie vol 305 no 7 pp486ndash493 1972

[11] R S Prasad and S Dev ldquoChemistry of ayurvedic crude drugsmdashIV guggulu (resin from commiphora mukulmdash4 absolute stere-ochemistry of mukulolrdquo Tetrahedron vol 32 no 12 pp 1437ndash1441 1976

[12] V D Patil U R Nayak and S Dev ldquoChemistry of ayurvediccrude drugsmdashII Guggulu (resin from Commiphora mukul)-2diterpenoid constituentsrdquo Tetrahedron vol 29 no 2 pp 341ndash348 1973

[13] J A Francis S N Raja and M G Nair ldquoBioactive terpenoidsand guggulusteroids from Commiphora mukul gum resin ofpotential anti-inflammatory interestrdquo Chemistry and Biodiver-sity vol 1 no 11 pp 1842ndash1853 2004

[14] H Matsuda T Morikawa S Ando et al ldquoAbsolute stere-ostructures of polypodane-type triterpenes myrrhanol A andmyrrhanone A from guggul-gum resin (the resin of Balsamod-endron mukul)rdquo Chemical and Pharmaceutical Bulletin vol 52no 10 pp 1200ndash1203 2004

[15] I Kimura M Yoshikawa S Kobayashi et al ldquoNew triterpenesmyrrhanol A and myrrhanone A from guggul-gum resins andtheir potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of micerdquo Bioorganic andMedicinal ChemistryLetters vol 11 no 8 pp 985ndash989 2001

[16] J Xu Y Guo P Zhao et al ldquoNeuroprotective cadinanesesquiterpenes from the resinous exudates of Commiphoramyrrhardquo Fitoterapia vol 82 no 8 pp 1198ndash1201 2011

[17] L O Hanus T Rezankab V M Dembitskya and A Mous-saieffa ldquoMyrrhmdashCommiphora chemistryrdquo Biomedical Papersvol 149 no 1 pp 3ndash28 2005

[18] V D Patil U R Nayak and S Dev ldquoChemistry of Ayurvediccrude drugsmdashI Guggulu (resin from Commiphora mukul)mdash1 steroidal constituentsrdquo Tetrahedron vol 28 no 8 pp 2341ndash2352 1972

[19] K K Purushothaman and S Chandrasekharan ldquoGuggulsterolsfrom Commiphora mukul (Burseraceae)rdquo Indian Journal ofChemistry Section B vol 14 pp 802ndash804 1976

[20] A G Bajaj and S Dev ldquoChemistry of ayurvedic crude drugsmdashV Guggulu (resin from Commiphora mukul)mdash5 some new

steroidal components and stereochemistry of guggulsterol-I atC-20 and C-22rdquo Tetrahedron vol 38 no 19 pp 2949ndash29541982

[21] M O Fatope S K S Al-Burtomani J O Ochei A OAbdulnour S M Z Al-Kindy and Y Takeda ldquoMuscanone a3-O-(1101584010158408101584010158401410158401015840-trimethylhexadecanyl) naringenin from Com-miphora wightiirdquo Phytochemistry vol 62 pp 1251ndash1255 2003

[22] H K Kakrani ldquoFlavonoids from the flowers of Commiphoramukulrdquo Fitoterapia vol 52 no 5 pp 221ndash223 1981

[23] V Kumar and S Dev ldquoChemistry of ayurvedic crude drugsmdashVII guggulu (resin from Commiphora mukul)mdash6 absolutestereochemistry of guggultetrolsrdquo Tetrahedron vol 43 no 24pp 5933ndash5948 1987

[24] S-L Su J-A Duan Y-P Tang et al ldquoIsolation and biologicalactivities of neomyrrhaol and other terpenes from the resin ofCommiphoramyrrhardquo PlantaMedica vol 75 no 4 pp 351ndash3552009

[25] H Matsuda T Morikawa S Ando et al ldquoAbsolute stereostruc-tures of polypodane- and octanordammarane-type triterpeneswith nitric oxide production inhibitory activity from guggul-gum resinsrdquo Bioorganic and Medicinal Chemistry vol 12 no 11pp 3037ndash3046 2004

[26] S Bose and K C Gupta ldquoStructure of Commiphora mukul gumI nature of sugars present and the structure of aldobiouronicacidrdquo Indian Journal of Chemistry Section A vol 2 pp 57ndash601966

[27] M A Ali and M Hasan ldquoChemical investigation of Com-miphora mukul Engl (Burseraceae)rdquo Pakistan Journal of Scien-tific and Industrial Research vol 10 pp 21ndash23 1967

[28] G V Satyavati ldquoGuggulipid a promising hypolipidemic agentfrom gum guggul (Commiphora wightii)rdquo Economic andMedic-inal Plant Research vol 5 pp 48ndash82 1991

[29] Sushruta Samhita chapter 15 Chowkamba Sanskrit SirijaVaranasi India 1954

[30] G Pandey Dravyaguna Vijnana Chaukhambla OrientaliaVaranasi India 2nd edition 2004

[31] S Dev ldquoA modern look at an age old ayurvedic drug guggulurdquoScience Age vol 5 pp 13ndash18 1987

[32] J Anurekha and V B Gupta ldquoChemistry and pharmacologicalprofile of guggulumdasha reviewrdquo Indian Journal of TraditionalKnowledge vol 5 pp 478ndash483 2006

[33] G V Satyavati ldquoGum guggul (Commiphora mukul)mdashthe suc-cess story of an ancient insight leading to a modern discoveryrdquoIndian Journal of Medical Research vol 87 no 4 pp 327ndash3351988

[34] S M de Morais V A Facundo L M Bertini et al ldquoChemicalcomposition and larvicidal activity of essential oils from piperspeciesrdquo Biochemical Systematics and Ecology vol 35 no 10 pp670ndash675 2007

[35] S Sahni C A Hepfinger and K A Sauer ldquoGuggulipid usein hyperlipidemia case report and review of the literaturerdquoAmerican Journal of Health-System Pharmacy vol 62 no 16pp 1690ndash1692 2005

[36] S Nityanand J S Srivastava and O P Asthana ldquoClinical trialswith gugulipidmdasha new hypolipidaemic agentrdquo The Journal ofthe Association of Physicians of India vol 37 no 5 pp 323ndash3281989

[37] S K Verma and A Bordia ldquoEffect of Commiphora mukul (gumguggulu) in patients of hyperlipidemia with special reference toHDL-cholesterolrdquo Indian Journal of Medical Research vol 87no 4 pp 356ndash360 1988

Scientifica 13

[38] G V Satyavati C Dwarakanath and S N Tripathi ldquoExper-imental studies on the hypocholesterolemic effect of Com-miphora mukulrdquoThe Indian Journal of Medical Research vol 57no 10 pp 1950ndash1962 1969

[39] V Baldwa V Bhasin P Ranka and K Mathur ldquoEffectsof Commiphora mukul (guggulu) in experimentally inducedhyperlipemia and atherosclerosisrdquoThe Journal of theAssociationof Physicians of India vol 29 no 1 pp 13ndash17 1981

[40] R S Hasani N Nayebi LMoradi AMehri B Larijani andMAbdollahi ldquoThe efficacy and safety of herbal medicines used inthe treatment of hyperlipidemia a systematic reviewrdquo CurrentPharmaceutical Design vol 16 no 26 pp 2935ndash2947 2010

[41] R Chander A K Khanna and N K Kapoor ldquoLipid loweringactivity of guggulsterone from Commiphora mukul in hyperli-paemic ratsrdquo Phytotherapy Research vol 10 no 6 pp 508ndash5111996

[42] JWu C Xia JMeier S Li X Hu andD S Lala ldquoThe hypolipi-demic natural product guggulsterone acts as an antagonist ofthe bile acid receptorrdquo Molecular Endocrinology vol 16 no 7pp 1590ndash1597 2002

[43] N L Urizar A B Liverman D T Dodds et al ldquoA naturalproduct that lowers cholesterol as an antagonist ligand for FXRrdquoScience vol 296 no 5573 pp 1703ndash1706 2002

[44] B-Z Yu R Kaimal S Bai et al ldquoEffect of guggulsteroneand cembranoids of Commiphora mukul on pancreatic phos-pholipase A

2 role in hypocholesterolemiardquo Journal of Natural

Products vol 72 no 1 pp 24ndash28 2009[45] L Mester M Mester and S Nityanand ldquoInhibition of platelet

aggregation by lsquoguggulursquo steroidsrdquo Planta Medica vol 37 no 4pp 367ndash369 1979

[46] A Bordia and S K Chuttani ldquoEffect of gum guggula onfibrinolysis and platelet adhesiveness in coronary heart diseaserdquoIndian Journal of Medical Research vol 70 no 6 pp 992ndash9961979

[47] S Panda and A Kar ldquoGugulu (Commiphora mukul) inducestriiodothyronine production possible involvement of lipidperoxidationrdquo Life Sciences vol 65 no 12 pp 137ndash141 1999

[48] Y B Tripathi O P Malhotra and S N Tripathi ldquoThyroid stim-ulating action of Z-guggulsterone obtained from Commiphoramukulrdquo Planta Medica vol 50 no 1 pp 78ndash80 1984

[49] G Chaudhary ldquoPharmacological properties of Commiphorawightii Arn Bhandarimdashan overviewrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 3 pp 73ndash752012

[50] M L Gujral K Sareen K K Tangri M K Amma and AK Roy ldquoAntiarthritic and anti-inflammatory activity of gumguggul (Balsamodendron mukul Hook)rdquo Indian Journal ofPhysiology and Pharmacology vol 4 pp 267ndash273 1960

[51] D Khanna G Sethi K S Ahn et al ldquoNatural products as a goldmine for arthritis treatmentrdquoCurrent Opinion in Pharmacologyvol 7 no 3 pp 344ndash351 2007

[52] M Karan P Sarup V Suneja and K Vasisht ldquoEffect oftraditional ayurvedic purification processes (sodhanvidhi) ofguggulu on carrageenan-induced paw oedema in ratsrdquo Journalof Pharmaceutical and Biomedical Sciences vol 21 no 5 pp 1ndash52012

[53] R B Arora V Taneja R C Sharma and S K Gupta ldquoAnti-inflammatory studies on a crystalline steroid isolated fromCommiphora mukulrdquo Indian Journal of Medical Research vol60 no 6 pp 929ndash931 1972

[54] S Verma A Jain and V B Gupta ldquoSynergistic and sustainedanti-inflammatory activity of guguul with the ibuprofen apreliminary studyrdquo International Journal of Pharma and BioSciences vol 1 pp 1ndash7 2010

[55] B B Singh L C Mishra S P Vinjamury N Aquilina VJ Singh and N Shepard ldquoThe effectiveness of Commiphoramukul for osteoarthritis of the knee an outcomes studyrdquoAlternative Therapies in Health and Medicine vol 9 no 3 pp74ndash79 2003

[56] R Chander A K Khanna and R Pratap ldquoAntioxidant activ-ity of guggulsterone the active principle of guggulipid fromCommiphora mukulrdquo Journal of Medicinal and Aromatic PlantSciences vol 24 pp 371ndash375 2002

[57] R Bellamkonda K Rasineni S R Singareddy et al ldquoAnti-hyperglycemic and antioxidant activities of alcoholic extractof Commiphora mukul gum resin in streptozotocin induceddiabetic ratsrdquo Pathophysiology vol 18 no 4 pp 255ndash261 2011

[58] X Wang J Greilberger G Ledinski G Kager B Paigen andG Jurgens ldquoThe hypolipidemic natural product Commiphoramukul and its component guggulsterone inhibit oxidative mod-ification of LDLrdquo Atherosclerosis vol 172 no 2 pp 239ndash2462004

[59] R Chander F Rizvi A K Khanna and R Pratap ldquoCar-dioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol inducedmyocardial ischemia in rats acomparative studyrdquo Indian Journal of Clinical Biochemistry vol18 no 2 pp 71ndash79 2003

[60] N Zhu M M Rafi R S DiPaola et al ldquoBioactive constituentsfrom gum guggul (Commiphora wightii)rdquo Phytochemistry vol56 no 7 pp 723ndash727 2001

[61] D Xiao Y Zeng L Prakash V Badmaev M Majeed andS V Singh ldquoReactive oxygen species-dependent apoptosis bygugulipid extract of ayurvedic medicine plant Commiphoramukul in human prostate cancer cells is regulated by c-Jun N-terminal kinaserdquo Molecular Pharmacology vol 79 no 3 pp499ndash507 2011

[62] M K P Amma NMalhotra R K Suri O P Arya H M Daniand K Sareen ldquoEffect of oleoresin of gum guggul (Commiphoramukul) on the reproductive organs of female ratrdquo Indian Journalof Experimental Biology vol 16 no 9 pp 1021ndash1023 1978

[63] D M Thappa and J Dogra ldquoNodulocystic acne oral gugulipidversus tetracyclinerdquo Journal of Dermatology vol 21 no 10 pp729ndash731 1994

[64] B Sharma R Salunke S Srivastava C Majumder and P RoyldquoEffects of guggulsterone isolated from Commiphora mukulin high fat diet induced diabetic ratsrdquo Food and ChemicalToxicology vol 47 no 10 pp 2631ndash2639 2009

[65] A Sharma V Kumar Patel S Rawat P Ramteke and R VermaldquoIdentification of the antibacterial component of some Indianmedicinal plants against klebsiella pneumoniaerdquo InternationalJournal of Pharmacy and Pharmaceutical Sciences vol 2 no 3pp 123ndash127 2010

[66] P Goyal A Chauhan and P Kaushik ldquoAssessment of Com-miphora wightii (Arn) Bhandari (Guggul) as potential sourcefor antibacterial agentrdquo Journal of Medicine and Medical Sci-ences vol 1 no 3 pp 71ndash75 2010

[67] K B Ishnava Y N Mahida and J S S Mohan ldquoIn vitroassessments of antibacterial potential of Commiphora wightii(Arn) Bhandari gum extractrdquo Journal of Pharmacognosy andPhytotherapy vol 2 no 7 pp 91ndash96 2010

[68] C D Romero S F Chopin G Buck E Martinez M Garciaand L Bixby ldquoAntibacterial properties of common herbal

14 Scientifica

remedies of the southwestrdquo Journal of Ethnopharmacology vol99 no 2 pp 253ndash257 2005

[69] L A Nohr L B Rasmussen and J Straand ldquoResin fromthe mukul myrrh tree guggul can it be used for treatinghypercholesterolemia A randomized controlled studyrdquo Com-plementary Therapies in Medicine vol 17 no 1 pp 16ndash22 2009

[70] P O Szapary M L Wolfe L T Bloedon et al ldquoGuggulipidfor the treatment of hypercholesterolemia a randomized con-trolled trialrdquo Journal of the American Medical Association vol290 no 6 pp 765ndash772 2003

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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PeptidesInternational Journal of


Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

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Zoology


Molecular Biology International

GenomicsInternational Journal of


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BioinformaticsAdvances in

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Evolutionary BiologyInternational Journal of



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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Genetics Research International


Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational



Enzyme Research



Microbiology

2 Scientifica

(1) 120572-Camphorene (2) Cembrene-A

Figure 1

urine and cowmilk It is possible that some of the properties(chemical and biological) of shodhan materials are added toguggulu during the purification process It is also possible thatsome of the toxic or harmful constituents of raw guggulu areneutralized detoxified or removed during this process

There are a large number of commercial polyherbal anti-inflammatory formulations which are using guggulu as thechief ingredient [6] However no study has been done toinvestigate the process of Ayurvedic purification and itsprobable effect on therapeutic efficacy except for one reportwhich states that gastric irritancy of guggulu is reduced withpurification [7]

During the process of purification foreign matter isremoved from raw guggulu manually and is then brokeninto small pieces The broken mass is wrapped in a piece ofcloth (called potli) and hanged into an inert container (calleddola yantra) containing one of the recommended mediawhich are gomutra (cow urine) triphala kasaya (decoctionof triphala) vasapatra kasaya (decoction of Adhatoda vasicaleaves) vasapatra savrasa (aqueous extract ofAdhatoda vasicaleaves) dugdha (milk) and water The guggulu is keptimmersed while fluid is boiled till all the soluble matter ofguggulu is dissolved in the purifying vehicle The insolublepart of guggulu is taken out and discarded Further boiling iscontinued till guggulu solution forms a soft mass It is thenpoured out over a smooth wooden board smeared with cowghee or castor oil anddried in the sunThedriedmass is calledpurified guggulu (suddh guggulu) [1]

2 Phytoconstituents of Guggulu

Guggulu contains diterpenoids triterpenoids steroids long-chain aliphatic tetrols aliphatic esters ferulates lignanscarbohydrates and a variety of inorganic ions besides minoramounts of sesamin and other unidentified constituents

21 Volatile Oil and Its Terpenoidal Constituents

211 Monoterpenoids The gum resin of C wightii yieldsabout 04 of essential oil by steam distillation and its chiefcomponents are myrcene dimyrcene and polymyrcene [8]Other components of the oil are eugenol d-limonene 120572-pinene (plusmn) linalool cineole 120572-terpineol d-120572-phellandrenemethylheptanone bornyl acetate (plusmn) geraniol and someother unidentified compounds [9]

OH

(3) Cembrene (4) Mukulol

Figure 2

212 Sesquiterpenoids The gum resin of C wightii has beenreported to contain bicyclic sesquiterpene cadinene [9]

213 Diterpenoids Diterpenoid constituents from gugguluinclude 120572-camphorene (1) (Figure 1) [10] cembrene-A (2)(Figure 1) cembrene (3) (Figure 2) [10] and other cem-brenoids Cembrene-A is one of themost elementary tetraen-es derived from geranylgeranyl pyrophosphate by C-1 to C-14cyclization

Mukulol (allylcembrol) (4) (Figure 2) is a new cembranealcohol which was isolated from the aerial parts and alsofrom the resin of guggulu [11 12] The allylcembrol structurewas established by spectral analysis and mild dehydrationwhich yielded cembrene Other isolated cembrane typediterpenes include isocembrol (5) (Figure 3) and 4-epiisocembrol (6) (Figure 3) (1119864 4119864 8119864)-4814-Trimethyl-11-(1-methylethyl)4-methoxycyclotertradeca-148-triene (7)(Figure 3) (2119864 12119864)-2713-trimethyl-9-(1-methylethyl)-15-oxabicyclo [1210] pentadeca-212-diene-7-ol (8) (Figure 4)and (4119885 6119864)-47121515-pentamethylbicylco [931] pentade-ca-46-diene-12-ol (9) (Figure 4) were novel compoundsobtained by bioassay-guided isolation from hexane-solubleportion of the methanol extract of guggulu [13]

214 Triterpenoids Polypodane-type triperpenes myrrhan-ol A (10) (Figure 5) B (11) (Figure 5) and C (12) (Figure 5)myrrhanone A (13) (Figure 6) myrrhanone B (14) (Figure 6)[14 15] myrrhanone A acetate (15) (Figure 6) commipherol(16) (Figure 7) commipherin (17) (Figure 7) and octanor-dammarane triperpenoid epimansumbinol (18) (Figure 8)

Scientifica 3

OMe


R1

R1

R2

R2

CH3

CH3

Figure 3

O

OH

HO


Figure 4

R


R

OH

HO

CH3

CH2OH

Figure 5



R

O

R

(13) Myrrhanone A



OH

CH2OH

CH2OAc

Figure 6



4 Scientifica

R

OH

OH


CH2OH

Figure 7

HO

(18) Epimansumbinol

Figure 8












Scientifica 5

HO

H

H

H

HOOC

H


Figure 9

RH

OH


Figure 10

O

O


HR1

R1

R2

R2

CH3


Figure 11


O

H

OH


R1

R1

R2

R2

Figure 12



6 Scientifica

HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH


HO

OAc

O

H


OH

H

O

(32) Z-Guggulsterol

Figure 13






Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 3

OMe


R1

R1

R2

R2

CH3

CH3

Figure 3

O

OH

HO


Figure 4

R


R

OH

HO

CH3

CH2OH

Figure 5



R

O

R

(13) Myrrhanone A



OH

CH2OH

CH2OAc

Figure 6



4 Scientifica

R

OH

OH


CH2OH

Figure 7

HO

(18) Epimansumbinol

Figure 8












Scientifica 5

HO

H

H

H

HOOC

H


Figure 9

RH

OH


Figure 10

O

O


HR1

R1

R2

R2

CH3


Figure 11


O

H

OH


R1

R1

R2

R2

Figure 12



6 Scientifica

HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH


HO

OAc

O

H


OH

H

O

(32) Z-Guggulsterol

Figure 13






Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

4 Scientifica

R

OH

OH


CH2OH

Figure 7

HO

(18) Epimansumbinol

Figure 8












Scientifica 5

HO

H

H

H

HOOC

H


Figure 9

RH

OH


Figure 10

O

O


HR1

R1

R2

R2

CH3


Figure 11


O

H

OH


R1

R1

R2

R2

Figure 12



6 Scientifica

HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH


HO

OAc

O

H


OH

H

O

(32) Z-Guggulsterol

Figure 13






Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 5

HO

H

H

H

HOOC

H


Figure 9

RH

OH


Figure 10

O

O


HR1

R1

R2

R2

CH3


Figure 11


O

H

OH


R1

R1

R2

R2

Figure 12



6 Scientifica

HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH


HO

OAc

O

H


OH

H

O

(32) Z-Guggulsterol

Figure 13






Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

6 Scientifica

HO

OH

OH

OH

OH

OH

OHOH

O

OH

OOH


HO

OAc

O

H


OH

H

O

(32) Z-Guggulsterol

Figure 13






Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 7

O

H

O

O

OAc


O

H


O

O


HO

OH

OH

OHH3CO

Figure 14

O

OH

HO

OH O

O

(38) Muscanone

Figure 15




8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

8 Scientifica

O

O

(39) Quercetin

HO

OH

OH

OH

OH

Figure 16















Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 9

O

O

O

O

R

O

O

O

O





HO

HOHO

HOHO

HO

OH

OH

OHOH

OH

O

O

O

O

O


HOHO

HO

HO

HO

OH

OHOH

OHOH

OH

OH

OH

CH2OH

CH3

Figure 17

HH

H


n = 14

n = 13


OH OH OH H3C(H2C)n

OHOH

CH2OH

OH

n = 12

n = 14

Figure 18




10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

10 Scientifica

COO


OH OH

OH

OH

OH3C

(CH2)nCH3

Figure 19

O

O

HH

(51) Diayangambin

O

OO

O

O

O

13-benzodioxole]

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

OCH3


Figure 20












Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 11







6 Conclusions







Acknowledgment


References




12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

12 Scientifica




































Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Scientifica 13


































14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

14 Scientifica











Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology








Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Documents

Review Article Pharmacology and Phytochemistry of Oleo …downloads.hindawi.com/journals/scientifica/2015/138039.pdfReview Article Pharmacology and Phytochemistry of Oleo-Gum Resin