• Abstracts are presented below for clinical studies on Guggul.

  Botanical Name: Commiphora Mukul Ayurvedic Name: Guggulu Common Name: Guggul

  

  Plant Phytonutrient Profile

  ---

  1: Chem Biodivers. 2004 Nov;1(11):1842/​53.

  Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of potential anti/​inflammatory interest.

  Francis JA, Raja SN, Nair MG.

  Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.

  Guggulu, the gum resin from Commiphora mukul, is one of the components of various formulations of traditional Ayurvedic medicine to treat inflammation, obesity, and lipid disorders. In most preparations of Ayurvedic medicine in India, guggulu is boiled prior to its use. Therefore, guggulu was boiled with H2O prior to extractions in our study. Bioassay/​guided isolation of compounds from the hexane/​soluble portion of the MeOH extract of guggulu yielded cembrenoids, 1/​6, a bicyclic diterpene, 7, guggulusterone derivatives, 8/​11, myrrhanone derivatives, 12, myrrhanol derivative, 13, and a lignan, 14. The structures of these compounds were confirmed by spectroscopic methods. Compounds 5, 6, 7, 10, and 12/​14 are novel. These compounds were assayed for lipid peroxidation and cyclooxygenase (COX) enzyme inhibitory activities. At 100 ppm, compounds 3, 6, and 14 inhibited the lipid peroxidation by 79, 57, and 58%, respectively, and the rest of isolated compounds showed 20/​40% inhibitory activity with respect to the controls. In COX/​1 and COX/​2 enzyme inhibitory assays, compound 3 showed 79 and 83%, and compound 8 gave 67 and 54% of inhibition, respectively, at 100 ppm. All fourteen compounds inhibited COX/​1 enzyme at 100 ppm. The lipid peroxidation and COX enzyme inhibitory activities exhibited by compounds isolated from C. mukul may substantiate its use in traditional medicine.

  Publication Types: Research Support, N.I.H., Extramural Research Support, Non/​U.S. Gov't

  PMID: 17191820 [PubMed /​ indexed for MEDLINE]

  
  

  2: Clin Cancer Res. 2006 Jan 15;12(2):662/​8.

  Guggulsterone inhibits osteoclastogenesis induced by receptor activator of nuclear factor/​kappaB ligand and by tumor cells by suppressing nuclear factor/​kappaB activation.

  Ichikawa H, Aggarwal BB.

  Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

  Bone resorption is commonly associated with aging and with certain types of cancer, including multiple myeloma and breast cancer. What induces bone resorption is not fully understood, but the role of osteoclasts is well established. Recently, receptor activator of nuclear factor/​kappaB (NF/​kappaB) ligand (RANKL), a member of the tumor necrosis factor superfamily, was implicated as a major mediator of bone resorption, suggesting that agents that can suppress RANKL signaling have the potential to inhibit bone resorption or osteoclastogenesis. Guggulsterone [4,17(20)/​pregnadiene/​3,16/​dione], isolated from the guggul tree Commiphora mukul and used to treat osteoarthritis and bone fractures, was recently shown to antagonize the farnesoid X receptor, decrease the expression of bile acid/​activated genes, and suppress the NF/​kappaB activation induced by various carcinogens. We investigated whether guggulsterone could modulate RANKL signaling and osteoclastogenesis induced by RANKL or tumor cells. We found that treatment of monocytes with guggulsterone suppressed RANKL/​activated NF/​kappaB activation (as indicated by gel/​shift assay) and that this suppression correlated with inhibition of IkappaBalpha kinase and phosphorylation and degradation of IkappaBalpha, an inhibitor of NF/​kappaB. Guggulsterone also suppressed the differentiation of monocytes to osteoclasts in a dose/​dependent and time/​dependent manner. Suppression of osteoclastogenesis by the NF/​kappaB/​specific inhibitory peptide implies a link between NF/​kappaB and osteoclastogenesis. Finally, differentiation to osteoclasts induced by coincubating human breast tumor cells (MDA/​MB/​468) or human multiple myeloma (U266) cells with monocytes was also completely suppressed by guggulsterone. Collectively, our results indicate that guggulsterone suppresses RANKL and tumor cell/​induced osteoclastogenesis by suppressing the activation of NF/​kappaB.

  Publication Types: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non/​P.H.S.

  PMID: 16428513 [PubMed /​ indexed for MEDLINE]

  
  

  3: Int Immunopharmacol. 2006 Feb;6(2):122/​32. Epub 2005 Jul 20.

  Inhibition of MAP kinases by crude extract and pure compound isolated from Commiphora mukul leads to down regulation of TNF/​alpha, IL/​1beta and IL/​2.

  Manjula N, Gayathri B, Vinaykumar KS, Shankernarayanan NP, Vishwakarma RA, Balakrishnan A.

  Centre for Biotechnology, Anna University, Chennai 600 025, India.

  The anti/​inflammatory effect of the medicinal plant, Commiphora mukul gum was studied in peripheral blood mononuclear cells (PBMC). Bioassay/​guided fractionation using conventional solvent extraction procedures, subsequent column fractionation, followed by monitoring specific activity in PBMC led to the isolation of a lead compound. Both crude ethyl acetate extract and the lead compound, thus isolated, showed inhibitory effect on proliferative response of PBMC in mitogenic lymphocyte proliferation and MLR assays. Further studies on inflammatory mediators such as IFN/​gamma, IL/​12, TNF/​alpha, IL/​1beta and NO showed down regulation, whereas no inhibition was observed in the case of anti/​inflammatory cytokine IL/​10. Immunoblot analysis revealed the inhibitory effect of crude ethyl acetate extract on phosphorylation of all the three mitogen activated protein kinases (MAPK) such as ERK, JNK and p38 MAPK. In contrast treatment with pure compound showed no inhibitory effect on ERK. c/​fos and c/​jun mRNA levels were also reduced in PMA stimulated cells on treatment with crude extract and pure compound. This reduction in c/​fos and c/​jun levels, when taken together with inhibition of MAPK activation, provides a possible mechanism by which both crude ethyl acetate extract and purified compound isolated from C. mukul exert its action.

  PMID: 16399617 [PubMed /​ indexed for MEDLINE]

  
  

  4: Complement Ther Med. 2005 Dec;13(4):279/​90. Epub 2005 Sep 23.

  Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration.

  Ulbricht C, Basch E, Szapary P, Hammerness P, Axentsev S, Boon H, Kroll D, Garraway L, Vora M, Woods J; Natural Standard Research Collaboration.

  Massachusetts General Hospital, USA. info@naturalstandard.com

  OBJECTIVE: To evaluate the scientific evidence on guggul for hyperlipidemia including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. METHODS: Electronic searches were conducted in nine databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on language or quality of publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanism of action. Standardized inclusion/exclusion criteria were utilized for selection. RESULTS: Before 2003, most scientific evidence suggested that guggulipid elicits significant reductions in serum total cholesterol, low/​density lipoprotein (LDL), and triglycerides, as well as elevations in high/​density lipoprotein (HDL) [Kotiyal JP, Bisht DB, Singh DS. Double blind cross/​over trial of gum guggulu (Commiphora mukul) Fraction A in hypercholesterolemia. J Res Indian Med Yoga Hom 1979;14(2):11/​6; Kotiyal JP, Singh DS, Bisht DB. Gum guggulu (Commiphora mukul) fraction 'A' in obesity/​a double/​blind clinical trial. J Res Ayur Siddha 1985;6(1, 3, 4):20/​35; Gaur SP, Garg RK, Kar AM, et al. Gugulipid, a new hypolipidaemic agent, in patients of acute ischaemic stroke: effect on clinical outcome, platelet function and serum lipids. Asia Pacif J Pharm 1997;12:65/​9; Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science 3 May 2002 [Science Express Reports]; Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989;37(5):323/​8; Kuppurajan K, Rajagopalan SS, Rao TK, et al. Effect of guggulu (Commiphora mukul/​Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26(5):367/​73; Gopal K, Saran RK, Nityanand S, et al. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India 1986;34(4):249/​51; Agarwal RC, Singh SP, Saran RK, et al. Clinical trial of gugulipid/​a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986;84:626/​34; Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL/​cholesterol. Indian J Med Res 1988;87:356/​60; Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 1994;8(4):659/​64; Ghorai M, Mandal SC, Pal M, et al. A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res 2000;14(3):200/​02]. However, most published studies were small and methodologically flawed. In August 2003, a well/​designed trial reported small significant increases in serum LDL levels associated with the use of guggul compared to placebo [Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290(6):765/​72]. No significant changes in total cholesterol, high/​density lipoprotein (HDL), or triglycerides were measured. These results are consistent with two prior published case reports [Das Gupta R. Gugulipid: pro/​lipaemic effect. J Assoc Physicians India 1990;38(12):346]. CONCLUSION: The effects of guggulipid in patients with high cholesterol are not clear, with some studies finding cholesterol/​lowering effects, and other research suggesting no benefits. At this time, there is not enough scientific evidence to support the use of guggul for any medical condition. Guggul may cause stomach discomfort or allergic rash as well as other serious side effects and interactions. It should be avoided in pregnant or breast/​feeding women and in children. Safety of use beyond 4 months has not been well studied.

  Publication Types: Review

  PMID: 16338199 [PubMed /​ indexed for MEDLINE]

  
  

  5: Mol Cancer Ther. 2005 Nov;4(11):1747/​54.

  Caspase/​dependent apoptosis induction by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, in PC/​3 human prostate cancer cells is mediated by Bax and Bak.

  Singh SV, Zeng Y, Xiao D, Vogel VG, Nelson JB, Dhir R, Tripathi YB.

  Department of Pharmacology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 2.32A Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213, USA. singhs@upmc.edu

  The present study was undertaken to gain insights into the molecular mechanism of cell death (apoptosis) by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, using PC/​3 human prostate cancer cells as a model. The viability of PC/​3 cells, but not a normal prostate epithelial cell line (PrEC), was reduced significantly on treatment with guggulsterone in a concentration/​dependent manner. Guggulsterone/​mediated suppression of PC/​3 cell proliferation was not due to perturbation in cell cycle progression but caused by apoptosis induction characterized by appearance of subdiploid cells and cytoplasmic histone/​associated DNA fragmentation. Guggulsterone/​induced apoptosis was associated with induction of multidomain proapoptotic Bcl/​2 family members Bax and Bak. Interestingly, the expression of antiapoptotic proteins Bcl/​2 and Bcl/​xL was initially increased in guggulsterone/​treated PC/​3 cells but declined markedly following a 16/​ to 24/​hour treatment with guggulsterone. Ectopic expression of Bcl/​2 in PC/​3 cells failed to confer significant protection against guggulsterone/​induced cell death. On the other hand, SV40 immortalized mouse embryonic fibroblasts derived from Bax/​Bak double knockout mice were significantly more resistant to guggulsterone/​induced cell killing compared with wild/​type cells. Guggulsterone treatment resulted in cleavage (activation) of caspase/​9, caspase/​8, and caspase/​3, and guggulsterone/​induced cell death was significantly attenuated in the presence of general caspase inhibitor as well as specific inhibitors of caspase/​9 and caspase/​8. In conclusion, the present study indicates that caspase/​dependent apoptosis by guggulsterone is mediated in part by Bax and Bak.

  Publication Types: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

  PMID: 16275996 [PubMed /​ indexed for MEDLINE]

  
  

  6: J Pharmacol Exp Ther. 2005 Jul;314(1):120/​7. Epub 2005 Apr 15.

  The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter.

  Ding X, Staudinger JL.

  Department of Pharmacology and Toxicology, University of Kansas, 1251 Wescoe Hall Dr., 5046 Malott Hall, Lawrence, KS 66045, USA.

  Guggulsterone is the active ingredient in gugulipid, an organic extract of the Commiphora mukul plant. Gugulipid has been used for nearly 3000 years in Ayurvedic medicine, mainly as a treatment for arthritis. Herbal practitioners currently use gugulipid therapy in conditions as diverse as rheumatism, coronary artery disease, arthritis, hyperlipidemia, acne, and obesity. The active ingredient in gugulipid is guggulsterone, a plant sterol compound recently identified as a pregnane X receptor (PXR; NR1I2) ligand. We show herein that guggulsterone treatment represses the expression of cytochrome P450 2b10 (Cyp2b10) gene expression by inhibiting constitutive androstane receptor (CAR; NR1I3) activity in hepatocytes lacking functional PXR (PXR/​knockout). We also show that PXR/​CAR cross/​talk determines the net activity of guggulsterone treatment toward Cyp2b10 gene expression. Using mammalian two/​hybrid assays, we show that treatment with guggulsterone differentially affects protein cofactor recruitment to these two nuclear receptors. These data identify guggulsterone as an inverse agonist of the nuclear receptor CAR. When viewed together with the data showing that PXR and CAR expression is highly variable in different ethnic populations and that CAR expression is under the control of a circadian rhythm, our data provide important insight into the molecular mechanism of interindividual variability of drug metabolism. These data, together with the recent resolution of the crystal structures of PXR and CAR, will likely aid in the rational design of more specific CAR inverse agonists that are currently viewed as potential antiobesity drugs.

  Publication Types: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

  PMID: 15833898 [PubMed /​ indexed for MEDLINE]

  
  

  7: Phytother Res. 2005 Jan;19(1):78/​80.

  Guggulu (Commiphora mukul) potentially ameliorates hypothyroidism in female mice.

  Panda S, Kar A.

  Thyroid Research Unit, School of Life Sciences, D. A. University, Khandwa Road, Indore/​452017 (M.P.), India.

  The efficacy of guggulu, the gum resin of Commiphora mukul in regulating hypothyroidism was evaluated in female mice. In addition to estimating serum levels of thyroxine and triiodothyronine, hepatic 5' monodeiodinase, hepatic glucose/​6/​phospatase and lipid/​peroxidation (LPO), the activities of the anti/​oxidative enzymes, superoxide dismutase (SOD) and catalase (CAT), were investigated. While 6/​n/​propyl/​2/​thiouracil (PTU, 10.00 mg/kg/d for 30 days) induced hypothyroidism in mice, as evidenced by a decrease in thyroid hormone concentration and in hepatic 5'D/​I activity, simultaneous administration of guggulu (200 mg/kg/d for 30 days) reversed this effect, indicating its potential to stimulate thyroid function. Although in PTU treated animals a marginal increase in hepatic LPO was observed, when simultaneously treated with guggulu, it was decreased. A parallel increase in the activity of endogenous antioxidants, SOD and CAT, in the latter group indicated the safe and antiperoxidative nature of the drug. These findings suggest the possible use of guggulu in the amelioration of hypothyroidism. Copyright (c) 2005 John Wiley & Sons, Ltd.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 15798994 [PubMed /​ indexed for MEDLINE]

  
  

  8: Mol Pharmacol. 2005 Mar;67(3):948/​54. Epub 2004 Dec 15.

  The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand.

  Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, Krishnan V, Bullock HA, Burris LL, Galvin RJ, Bramlett K, Stayrook KR.

  Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. burris@lilly.com

  Guggulsterone (GS) is the active substance in guggulipid, an extract of the guggul tree, Commiphora mukul, used to treat a variety of disorders in humans, including dyslipidemia, obesity, and inflammation. The activity of GS has been suggested to be mediated by antagonism of the receptor for bile acids, the farnesoid X receptor (FXR). Here, we demonstrate that both stereoisomers of the plant sterol, (E)/​ and (Z)/​GS, bind to the steroid receptors at a much higher affinity than to FXR. Both stereoisomers bind to the mineralocorticoid receptor (MR) with a Ki value of approximately 35 nM, which is greater than 100 times more potent than their affinity for FXR. Both (E)/​ and (Z)/​GS also displayed high affinity for other steroid receptors, including the androgen (AR), glucocorticoid (GR), and progesterone receptors (PR) with Ki values ranging from 224 to 315 nM. In cell/​based functional cotransfection assays, GSs behaved as antagonists of AR, GR, and MR, but as agonists of PR. Agonist activity was also demonstrated with estrogen receptor (ER) alpha; however, the potency was very low (EC50 > 5000 nM). In addition, GS displayed activity in functional assays in cell lines expressing endogenous AR, GR, ER, and PR. These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors.

  PMID: 15602004 [PubMed /​ indexed for MEDLINE]

  
  

  9: Chem Pharm Bull (Tokyo). 2004 Oct;52(10):1200/​3.

  Absolute stereostructures of polypodane/​type triterpenes, myrrhanol A and myrrhanone A, from guggul/​gum resin (the resin of Balsamodendron mukul).

  Matsuda H, Morikawa T, Ando S, Oominami H, Murakami T, Kimura I, Yoshikawa M.

  Kyoto Pharmaceutical University, Kyoto, Japan.

  Two new polypodane/​type triterpenes, myrrhanol A and myrrhanone A, were isolated from the 50% aqueous methanolic extract of guggul/​gum resin [the resin of Balsamodendron (=Commiphora) mukul HOOK]. The structures of the new constituents, including their absolute configurations, were determined on the basis of chemical and physicochemical evidence.

  PMID: 15467235 [PubMed /​ indexed for MEDLINE]

  
  

  10: J Pharm Biomed Anal. 2004 Sep 21;36(1):33/​41.

  HPTLC method for guggulsterone. I. Quantitative determination of E/​ and Z/​guggulsterone in herbal extract and pharmaceutical dosage form.

  Agrawal H, Kaul N, Paradkar AR, Mahadik KR.

  Department of Quality Assurance Techniques, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India.

  A sensitive, selective, precise and robust high/​performance thin/​layer chromatographic method of analysis of E and Z stereoisomers of guggulsterone (the hypolipidemic agent in the gum/​resin exudates of Commiphora mukul) both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F/​254 as the stationary phase. The solvent system consisted of toluene/​acetone (9:1, v/v). Densitometric analysis of guggulsterone was carried out in the absorbance mode at 250 nm. This system was found to give compact spots for E/​ and Z/​guggulsterone (Rf value of 0.38 +//​ 0.02 and 0.46 +//​ 0.02, respectively) following double development of chromatoplates with the same mobile phase. The linear regression analysis data for the calibration plots for E/​ and Z/​guggulsterone showed good linear relationship with r2 = 0.9977 +//​ 0.054 and 0.9975 +//​ 0.068, respectively, in the concentration range of 100/​6000 ng/spot. The mean value of slope and intercept were 0.11 +//​ 0.006 and 0.11 +//​ 0.005, 14.26 +//​ 0.56 and 10.92 +//​ 0.76, respectively, for E/​ and Z/​guggulsterone. The method was validated for precision, robustness and recovery. The limit of detection and quantitation were 12, 10 and 24, 20 ng/spot, respectively, for E/​ and Z/​guggulsterone. Statistical analysis proves that the method is repeatable and selective for the estimation of the said drug. Since the proposed mobile phase effectively resolves the E/​ and Z/​isomers of guggulsterone, this HPTLC method can be applied for identification and quantitation of these isomers in herbal extracts and pharmaceutical dosage form.

  Publication Types: Research Support, Non/​U.S. Gov't Validation Studies

  PMID: 15351045 [PubMed /​ indexed for MEDLINE]

  
  

  11: J Pharm Biomed Anal. 2004 Sep 21;36(1):23/​31.

  HPTLC method for guggulsterone. II. Stress degradation studies on guggulsterone.

  Agrawal H, Kaul N, Paradkar AR, Mahadik KR.

  Department of Quality Assurance Techniques, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra State, India.

  Stress degradation studies were carried out on guggulsterone (the hypolipidemic agent in the gum/​resin exudates of Commiphora mukul) following the conditions prescribed in the parent drug stability testing guideline (Q1AR) issued by International Conference on Harmonization (ICH). The present study describes degradation of guggulsterone under different ICH prescribed stress conditions (acid and base hydrolysis, oxidation, dry and wet heat degradation and photodegradation) and establishment of a stability indicating HPTLC assay. The method employed TLC aluminium plates precoated with silica gel 60F/​254 as the stationary phase. The solvent system consisted of toluene/​acetone (9:1, v/v). Densitometric analysis of guggulsterone was carried out in the absorbance mode at 250 nm. This system was found to give compact spots for E/​ and Z/​guggulsterone, (Rf value of 0.38 +//​ 0.02 and 0.46 +//​ 0.02, respectively) following double development of chromatoplates with the same mobile phase. The drug undergoes degradation under acidic and basic conditions, oxidation, dry and wet heat treatment and photodegradation. All the peaks of degraded products were resolved from the standard guggulsterone with significantly different Rf values. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 15351044 [PubMed /​ indexed for MEDLINE]

  
  

  12: J Biol Chem. 2004 Nov 5;279(45):47148/​58. Epub 2004 Aug 17.

  Guggulsterone inhibits NF/​kappaB and IkappaBalpha kinase activation, suppresses expression of anti/​apoptotic gene products, and enhances apoptosis.

  Shishodia S, Aggarwal BB.

  Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

  Guggulsterone, derived from Commiphora mukul and used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, has been recently shown to antagonize the farnesoid X receptor and decrease the expression of bile acid/​activated genes. Because activation of NF/​kappaB has been closely linked with inflammatory diseases affected by guggulsterone, we postulated that it must modulate NF/​kappaB activation. In the present study, we tested this hypothesis by investigating the effect of this steroid on the activation of NF/​kappaB induced by inflammatory agents and carcinogens. Guggulsterone suppressed DNA binding of NF/​kappaB induced by tumor necrosis factor (TNF), phorbol ester, okadaic acid, cigarette smoke condensate, hydrogen peroxide, and interleukin/​1. NF/​kappaB activation was not cell type/​specific, because both epithelial and leukemia cells were inhibited. Guggulsterone also suppressed constitutive NF/​kappaB activation expressed in most tumor cells. Through inhibition of IkappaB kinase activation, this steroid blocked IkappaBalpha phosphorylation and degradation, thus suppressing p65 phosphorylation and nuclear translocation. NF/​kappaB/​dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK was also blocked by guggulsterone but without affecting p65/​mediated gene transcription. In addition, guggulsterone decreased the expression of gene products involved in anti/​apoptosis (IAP1, xIAP, Bfl/​1/A1, Bcl/​2, cFLIP, and survivin), proliferation (cyclin D1 and c/​Myc), and metastasis (MMP/​9, COX/​2, and VEGF); this correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. Overall, our results indicate that guggulsterone suppresses NF/​kappaB and NF/​kappaB/​regulated gene products, which may explain its anti/​inflammatory activities.

  Publication Types: Research Support, Non/​U.S. Gov't Research Support, U.S. Gov't, Non/​P.H.S. Research Support, U.S. Gov't, P.H.S.

  PMID: 15322087 [PubMed /​ indexed for MEDLINE]

  
  

  13: Inflammopharmacology. 2004;12(2):131/​52.

  Anti/​inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis.

  Tripathi YB, Reddy MM, Pandey RS, Subhashini J, Tiwari OP, Singh BK, Reddanna P.

  Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi/​221005, India. Yamini30@sify.com

  BHUx is a polyherbal formulation consisting of water/​soluble fractions of five medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica). The present study was undertaken to evaluate its antioxidant and antiinflammatory effects. BHUx, standardized by HPLC fingerprinting and filtered through 0.2 microm filter paper, was employed for different studies under in vivo and in vitro conditions. Under in vivo conditions, BHUx significantly reduced inflammation in the carrageenan/​induced rat paw oedema model of inflammation, suggesting its anti/​inflammatory properties. In order to test the mechanism of action of BHUx, further in vitro studies were undertaken on cumene/​hydroperoxide/​induced lipid peroxidation (CHP) in liver homogenate, LPS/​induced NO production in peritoneal macrophages and on key enzymes of arachidonic acid cascade, involved in the mediation of inflammation. Under the conditions, BHUx showed concentration/​dependent inhibition of CHP/​induced lipid peroxidation in liver homogenate, suggesting its antioxidant properties. Similarly the potent anti/​inflammatory effects of BHUx are evident by (a) preferential inhibition of COX/​2 (IC50 for COX/​2 = 80 microg/ml and IC50 for COX/​1 = 169 microg/ml), (b) low ratios in the IC50 values of COX/​2/COX/​1 (0.47), (c) decreased production of NO in LPS/​induced peritoneal macrophages and (d) inhibition of 5/​LOX (IC50 = 795 microg/ml). BHUx also showed a preference for inhibiting 15/​lipoxygenase (IC50 = 44 microg/ml), a key enzyme implicated in LDL oxidation. These studies suggest that BHUx is acting mainly at three levels, i.e., as a potent natural antioxidant, by reduction of key inflammatory mediators of arachidonic acid cascade and by preventing 15/​LOX/​mediated LDL oxidations, to prevent atherosclerosis.

  Publication Types: Comparative Study Research Support, Non/​U.S. Gov't

  PMID: 15265316 [PubMed /​ indexed for MEDLINE]

  
  

  14: Ann Pharmacother. 2004 Jul/​Aug;38(7/​8):1222/​5. Epub 2004 Jun 8.

  Rhabdomyolysis caused by Commiphora mukul, a natural lipid/​lowering agent.

  Bianchi A, Cantu P, Firenzuoli F, Mazzanti G, Menniti/​Ippolito F, Raschetti R.

  Traditional Medicine Department, Centro di Orientamento Educativo, Barzio, Italy.

  OBJECTIVE: To report a case of rhabdomyolysis caused by Commiphora mukul, a natural lipid/​lowering agent. CASE SUMMARY: A 55/​year/​old man was taking an extract of C. mukul 300 mg 3 times daily to lower his cholesterol level. He developed rhabdomyolysis with hemoglobinuria after 2 weeks of treatment. Laboratory tests showed creatine kinase 144600 IU/L (reference range 24/​195), myoglobin >3000 ng/mL (28/​72), lactate dehydrogenase 7157 IU/L (230/​460), aspartate aminotransferase 1115 IU/L (10/​35), and alanine aminotransferase 205 IU/L (10/​35). Analysis of a urine sample was 2+ positive for hemoglobin. All parameters returned to normal after the herbal preparation was discontinued. DISCUSSION: The Naranjo probability scale indicates C. mukul as the possible cause of rhabdomyolysis in our patient. Drug/​induced rhabdomyolysis is an established but rare adverse effect of high doses of cholesterol/​lowering agents (statins) or interactions between drugs (eg, statins and fibrates). As of May 28, 2004, to our knowledge, this is the first reported case of rhabdomyolysis following C. mukul ingestion. CONCLUSIONS: Our report describes a case of rhabdomyolysis possibly caused by C. mukul and underlines the need for active surveillance of natural products.

  Publication Types: Case Reports Research Support, Non/​U.S. Gov't

  PMID: 15187214 [PubMed /​ indexed for MEDLINE]

  
  

  5: J Pharmacol Exp Ther. 2004 Aug;310(2):528/​35. Epub 2004 Apr 1.

  Guggulsterone activates multiple nuclear receptors and induces CYP3A gene expression through the pregnane X receptor.

  Brobst DE, Ding X, Creech KL, Goodwin B, Kelley B, Staudinger JL.

  Department of Pharmacology and Toxicology, University of Kansas, 5046 Malott Hall, Lawrence, KS 66045, USA.

  Gugulipid is an extract of the guggul tree, Commiphora mukul, that is used to treat hyperlipidemia in humans. The lipid/​lowering activity is found in the stereoisomers and plant sterols Z/​guggulsterone and E/​guggulsterone. The molecular basis for the lipid/​lowering action of guggulsterone has been suggested to be antagonism of the farnesoid X receptor, a member of the nuclear receptor superfamily of ligand/​activated transcription factors. To determine whether guggulsterone has the ability to function as an agonist of other nuclear receptor family members, we screened a panel of these proteins for their ability to transactivate reporter genes. Here, we show that guggulsterones activate the estrogen receptor alpha isoform, progesterone receptor, and pregnane X receptor. Concentration/​response analysis using reporter gene assays indicate that guggulsterones activate these three receptors with EC(50) values in the low micromolar range. Furthermore, we show that guggulsterone/​mediated activation of the pregnane X receptor induces the expression of CYP3A genes in both rodent and human hepatocytes. Protein interaction assays indicate that guggulsterones interact directly with pregnane X receptor, thereby modulating interaction with protein cofactors. We introduce a novel method to screen herbal remedies for their ability to activate pregnane X receptor. Pregnane X receptor activation is known to cause herb/​drug interactions, and our data suggest that gugulipid therapy should be used cautiously in patients taking prescription medications that are metabolized by CYP3A family members. Moreover, our data suggest the need for additional studies of guggulsterones agonist activity against estrogen receptor alpha isoform and the progesterone receptor.

  Publication Types: Comparative Study Research Support, U.S. Gov't, P.H.S.

  PMID: 15075359 [PubMed /​ indexed for MEDLINE]

  
  

  16: Fitoterapia. 2004 Mar;75(2):204/​8.

  Antibacterial activities of some constituents from oleo/​gum/​resin of Commiphora mukul.

  Saeed MA, Sabir AW.

  Department of Pharmacy, University of the Punjab (Allama Iqbal Campus), Lahore/​54000, Pakistan. moasif1605@hotmail.com

  The essential oil, chloroform extract and seven sesquiterpenoids compounds newly isolated from the oleo/​gum/​resin of Commiphora mukul showed a wide range of inhibiting activity against both Gram (+) and Gram (/​) bacteria.

  PMID: 15030926 [PubMed /​ indexed for MEDLINE]

  
  

  17: Atherosclerosis. 2004 Feb;172(2):239/​46.

  The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL.

  Wang X, Greilberger J, Ledinski G, Kager G, Paigen B, Jurgens G.

  The Jackson Laboratory, Bar Harbor, ME 04609, USA. xw@jax.org

  There is accumulating evidence that LDL oxidation is essential for atherogenesis, and that antioxidants that prevent this oxidation may either slow down or prevent atherogenesis. In the present study, we found that Commiphora mukul and its cholesterol/​lowering component, guggulsterone, effectively inhibited LDL oxidation mediated by either catalytic copper ions, free radicals generated with the azo compound 2,2'/​azobis/​(2/​amidinopropane)dihydrochloride (AAPH), soybean lipoxygenase enzymatically, or mouse peritoneal macrophages. This inhibition was assessed by the decrease in the following parameters describing LDL oxidation: conjugated dienes, relative electrophoretic mobility (REM), thiobarbituric acid reactive substances, lipid hydroperoxides, oxidation/​specific immune epitopes as detected with a monoclonal antibody against oxidized LDL, and the accumulation of LDL derived cholesterol esters in mouse peritoneal macrophages. We concluded that C. mukul and its lipid/​lowering component, guggulsterone, significantly inhibit LDL oxidation. The combination of antioxidant and lipid/​lowering properties of C. mukul and guggulsterone makes them especially beneficial against atherogenesis.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 15019533 [PubMed /​ indexed for MEDLINE]

  
  

  18: Phytomedicine. 2003;10(6/​7):474/​82.

  Antiatherogenic effect of Caps HT2, a herbal Ayurvedic medicine formulation.

  Mary NK, Babu BH, Padikkala J.

  Amala Cancer Research Centre, Thrissur, Kerala, India.

  The antiatherogenic effect of a herbal formulation, Caps HT2, was evaluated as antioxidant, anticoagulant, platelet antiaggregatory, lipoprotein lipase releasing, anti/​inflammatory and hypolipidaemic activity in rats. The formulation contained the methanolic extracts of selected parts of plants, Commiphora mukul, Allium sativum, Plumbago indica, Semecarpus anacardium, Hemidesmus indicus, Terminalia arjuna, Tinospora cordifolia, Withania somnifera and Ocimum sanctum. The formulation, Caps HT2 was found to scavenge superoxide and hydroxyl radicals; the IC50 required being 55.0 and 610.0 microg/ml respectively. The lipid peroxidation was found inhibited (50%) by 48.5 microg/ml of Caps HT2. The intravenous administration of the formulation (5 mg/kg) delayed the plasma recalcification time in rabbits and enhanced the release of lipoprotein lipase enzyme significantly (p < 0.001). The formulation also inhibited ADP induced platelet aggregation in vitro, which was comparable to commercial heparin. The anti/​inflammatory action of the formulation was significant (p < 0.001) with acute and chronic inflammations induced by carrageenan and formalin respectively in rats. The hypolipidaemic effect of Caps HT2 was significant (p < 0.001) with the administration of the formulation, in diet/​induced hyperlipidaemia of rats for a period of 30 days. Oral administration of the formulation, Caps HT2 (100, 200, 300 and 400 mg/kg) significantly raised HDL cholesterol levels. The atherogenic index and the reduction in body weight were significant indicating the effectiveness against hyperlipidaemia and obesity. All these results revealed the therapeutic potential of Caps HT2 against vascular intimal damage and atherogenesis leading to various types of cardiovascular problems.

  PMID: 13678230 [PubMed /​ indexed for MEDLINE]

  
  

  19: JAMA. 2003 Aug 13;290(6):765/​72.

  Comment in: JAMA. 2003 Dec 3;290(21):2800/​1; author reply 2801. JAMA. 2003 Dec 3;290(21):2800; author reply 2801.

  Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial.

  Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD, Rader DJ.

  Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104/​6021, USA. szapary@mail.med.upenn.edu

  CONTEXT: Herbal extracts from Commiphora mukul (guggul) have been widely used in Asia as cholesterol/​lowering agents, and their popularity is increasing in the United States. Recently, guggulsterones, the purported bioactive compounds of guggul, have been shown to be potent antagonists of 2 nuclear hormone receptors involved in cholesterol metabolism, establishing a plausible mechanism of action for the hypolipidemic effects of these extracts. However, there are currently no published safety or efficacy data on the use of guggul extracts in Western populations. OBJECTIVE: To study the short/​term safety and efficacy of 2 doses of a standardized guggul extract (guggulipid, containing 2.5% guggulsterones) in healthy adults with hyperlipidemia eating a typical Western diet. DESIGN: Double/​blind, randomized, placebo/​controlled trial using a parallel design, conducted March 2000/​August 2001. PARTICIPANTS AND SETTING: A total of 103 ambulatory, community/​dwelling, healthy adults with hypercholesterolemia in the Philadelphia, Pa, metropolitan area. INTERVENTION: Oral, 3 times daily doses of standard/​dose guggulipid (1000 mg), high/​dose guggulipid (2000 mg), or matching placebo. MAIN OUTCOME MEASURES: Percentage change in levels of directly measured low/​density lipoprotein cholesterol (LDL/​C) after 8 weeks of therapy. Secondary outcome measures included levels of total cholesterol, high/​density lipoprotein cholesterol (HDL/​C), triglycerides, and directly measured very low/​density lipoprotein cholesterol (VLDL/​C), as well as adverse events reports and laboratory safety measures including electrolyte levels and hepatic and renal function. RESULTS: Compared with participants randomized to placebo (n = 36), in whom levels of LDL/​C decreased by 5%, both standard/​dose guggulipid (n = 33) and high/​dose guggulipid (n = 34) raised levels of LDL/​C by 4% (P =.01 vs placebo) and 5% (P =.006 vs placebo), respectively, at 8 weeks, for a net positive change of 9% to 10%. There were no significant changes in levels of total cholesterol, HDL/​C, triglycerides, or VLDL/​C in response to treatment with guggulipid in the intention/​to/​treat analysis. While guggulipid was generally well tolerated, 6 participants treated with guggulipid developed a hypersensitivity rash compared with none in the placebo group. CONCLUSIONS: Despite plausible mechanisms of action, guggulipid did not appear to improve levels of serum cholesterol over the short term in this population of adults with hypercholesterolemia, and might in fact raise levels of LDL/​C. Guggulipid also appeared to cause a dermatologic hypersensitivity reaction in some patients.

  Publication Types: Clinical Trial Randomized Controlled Trial Research Support, Non/​U.S. Gov't Research Support, U.S. Gov't, P.H.S.

  PMID: 12915429 [PubMed /​ indexed for MEDLINE]

  
  

  20: J Fam Pract. 2003 Jun;52(6):468/​78.

  Herbs for serum cholesterol reduction: a systematic view.

  Thompson Coon JS, Ernst E.

  Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. jo.thompson/​coon@pms.ac.uk

  OBJECTIVES: To systematically review the clinical evidence for herbal medicinal products in the treatment of hypercholesterolemia. STUDY DESIGN: A systematic review of randomized clinical trials of herbal medicinal products used to lower serum cholesterol. Systematic literature searches were conducted in 6 electronic data/​bases. The reference lists of all papers and our files were searched for more relevant publications. Experts in the field and manufacturers of identified herbal medicinal products were contacted for published and unpublished data. No language restrictions were imposed. OUTCOMES MEASURED: All randomized clinical trials of serum cholesterol reduction, in which mono/​preparations of herbal medicinal products were administered as supplements to human subjects, were included. RESULTS: Twenty/​five randomized clinical trials involving 11 herbal medicinal products were identified. Guggul (Commiphora mukul), fenugreek (Trigonella foenum/​graecum), red yeast rice, and artichoke (Cynara scolymus) have been most extensively studied and have demonstrated reductions in total serum cholesterol levels of between10% and 33%. The methodological quality as assessed by the Jadad score was less than 3 (maximum, 5) for 13 of the 25 trials. CONCLUSIONS: Many herbal medicinal products have potential hypocholesterolemic activity and encouraging safety profiles. However, only a limited amount of clinical research exists to support their efficacy. Further research is warranted to establish the value of these extracts in the treatment of hypercholesterolemia.

  Publication Types: Research Support, Non/​U.S. Gov't Review

  PMID: 12791229 [PubMed /​ indexed for MEDLINE]

  
  

  21: Altern Ther Health Med. 2003 May/​Jun;9(3):74/​9.

  The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study.

  Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ, Shepard N.

  Southern California University of Health Sciences, USA.

  CONTEXT: Ayurveda, the traditional system of healthcare in India, has many remedies for Osteoarthritis (OA). One of the ingredients most commonly found in Ayurvedic arthritis formulas is guggul, an oleoresin of the herb Commiphora mukul (CM). The authors have conducted both preclinical and clinical investigations of guggul for reduction of pain, stiffness, and improved function, and to determine tolerability in older patients with a diagnosis of OA of the knee. METHODS: The study was conducted using an outcome, quasi/​experimental, model. Thirty male and female participants meeting the inclusion/exclusion criteria, with a score of 2 or more on the Kellegran/​Lawrence scale for at least 1 knee, were admitted in the study. CM was administered in capsule form (500 mg concentrated exact delivered TID) along with food. The WOMAC Total Score was used as a primary outcome measure. VAS scales, 6/​minute walk/​test, and WOMAC subscales were used as outcome measures. RESULTS: At the end of treatment, there was a significant difference in the scores of the primary and secondary outcome measures. On the primary measure, WOMAC total score, participants were significantly improved (P < 0.0001) after taking the supplement for 1 month and continued to improve at the 2/​month marker and follow/​up. Secondary measures of pain in the VAS format demonstrated participant improvement; however, mood state, and current pain were not significantly different (P < 0.05) than baseline until the 2 month assessment (P < 0.001). CONCLUSIONS: Overall data indicate significant improvement for participants during the trial in both scales and objective measures used for assessment purposes. There were no side effects reported during the trial. CM appears to be a relatively safe and effective supplement to reduce symptoms of OA.

  Publication Types: Clinical Trial

  PMID: 12776478 [PubMed /​ indexed for MEDLINE]

  
  

  22: Annu Rev Nutr. 2003;23:303/​13. Epub 2003 Feb 26.

  GUGULIPID: a natural cholesterol/​lowering agent.

  Urizar NL, Moore DD.

  Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. nurizar@bcm.tmc.edu

  The resin of the Commiphora mukul tree has been used in Ayurvedic medicine for more than 2000 years to treat a variety of ailments. Studies in both animal models and humans have shown that this resin, termed gum guggul, can decrease elevated lipid levels. The stereoisomers E/​ and Z/​guggulsterone have been identified as the active agents in this resin. Recent studies have shown that these compounds are antagonist ligands for the bile acid receptor farnesoid X receptor (FXR), which is an important regulator of cholesterol homeostasis. It is likely that this effect accounts for the hypolipidemic activity of these phytosteroids.

  Publication Types: Research Support, U.S. Gov't, P.H.S. Review

  PMID: 12626688 [PubMed /​ indexed for MEDLINE]

  
  

  23: J Biol Chem. 2003 Mar 21;278(12):10214/​20. Epub 2003 Jan 13.

  Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump.

  Cui J, Huang L, Zhao A, Lew JL, Yu J, Sahoo S, Meinke PT, Royo I, Pelaez F, Wright SD.

  Department of Atherosclerosis and Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA. jisong_cui@merck.com

  Guggulipid is an extract of the guggul tree Commiphora mukul and has been widely used to treat hyperlipidemia in humans. The plant sterol guggulsterone (GS) is the active agent in this extract. Recent studies have shown that GS can act as an antagonist ligand for farnesoid X receptor (FXR) and decrease expression of bile acid/​activated genes. Here we show that GS, although an FXR antagonist in coactivator association assays, enhances FXR agonist/​induced transcription of bile salt export pump (BSEP), a major hepatic bile acid transporter. In HepG2 cells, in the presence of an FXR agonist such as chenodeoxycholate or GW4064, GS enhanced endogenous BSEP expression with a maximum induction of 400/​500% that induced by an FXR agonist alone. This enhancement was also readily observed in FXR/​dependent BSEP promoter activation using a luciferase reporter construct. In addition, GS alone slightly increased BSEP promoter activation in the absence of an FXR agonist. Consistent with the results in HepG2, guggulipid treatment in Fisher rats increased BSEP mRNA. Interestingly, in these animals expression of the orphan nuclear receptor SHP (small heterodimer partner), a known FXR target, was also significantly increased, whereas expression of other FXR targets including cholesterol 7alpha/​hydroxylase (Cyp 7a1), sterol 12alpha/​hydroxylase (Cyp 8b1), and the intestinal bile acid/​binding protein (I/​BABP), remained unchanged. Thus, we propose that GS is a selective bile acid receptor modulator that regulates expression of a subset of FXR targets. Guggulipid treatment in rats lowered serum triglyceride and raised serum high density lipoprotein levels. Taken together, these data suggest that guggulsterone defines a novel class of FXR ligands characterized by antagonist activities in coactivator association assays but with the ability to enhance the action of agonists on BSEP expression in vivo.

  PMID: 12525500 [PubMed /​ indexed for MEDLINE]

  
  

  24: Mol Endocrinol. 2002 Jul;16(7):1590/​7.

  The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor.

  Wu J, Xia C, Meier J, Li S, Hu X, Lala DS.

  Department of Biotechnology, Pharmacia Corp., St. Louis, Missouri 63198, USA.

  Ayurveda, the ancient Indian system of health care and medicine, has a well/​organized materia medica in which plants form a dominant part. A key illustration of the exploitation of this knowledge toward the development of a modern drug is the isolation and characterization of two antihyperlipidemic compounds, Z/​, and E/​guggulsterone from the tree Commiphora mukul, the exudate of which has been traditionally used for mitigating lipid disorders. Here, we demonstrate that Z/​guggulsterone and an analog, 80/​574 currently in clinical trials, act as antagonists of the bile acid receptor (BAR), a member of the intracellular receptor superfamily. These compounds antagonize the activity of BAR in vitro, and in cell culture systems on promoters and endogenous target genes. In biochemical assays, they are able to displace coactivator peptides from the receptor in a dose/​dependent manner. The mechanism by which they act as BAR antagonists is likely through their inability to recruit coactivator proteins, failure to release corepressor proteins from unliganded receptor, and ability to compete with BAR agonists to block coactivator recruitment. Our data suggest these compounds may mediate at least some of their effects via the BAR.

  PMID: 12089353 [PubMed /​ indexed for MEDLINE]

  
  

  25: Science. 2002 May 31;296(5573):1703/​6. Epub 2002 May 2.

  A natural product that lowers cholesterol as an antagonist ligand for FXR.

  Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD.

  Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.

  Extracts of the resin of the guggul tree (Commiphora mukul) lower LDL (low/​density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone [4,17(20)/​pregnadiene/​3,16/​dione] is the active agent in this extract. We show that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone treatment decreases hepatic cholesterol in wild/​type mice fed a high/​cholesterol diet but is not effective in FXR/​null mice. Thus, we propose that inhibition of FXR activation is the basis for the cholesterol/​lowering activity of guggulsterone. Other natural products with specific biologic effects may modulate the activity of FXR or other relatively promiscuous nuclear hormone receptors.

  Publication Types: Research Support, Non/​U.S. Gov't Research Support, U.S. Gov't, Non/​P.H.S. Research Support, U.S. Gov't, P.H.S.

  PMID: 11988537 [PubMed /​ indexed for MEDLINE]

  
  

  26: Eur J Nutr. 2001 Jun;40(3):127/​33.

  Investigations on possible serotonergic involvement in effects of OB/​200G (polyherbal preparation) on food intake in female mice.

  Kaur G, Kulkarni SK.

  Pharmacology Division, Univ Inst Pharm Sci, Panjab University, Chandigarh, India.

  BACKGROUND: OB/​200G is a polyherbal preparation containing aqueous extracts of Garcinia cambogia, Gymnema sylvestre, Zingiber officinale, Piper longum and resin from Commiphora mukul, all possessing thermogenic properties. Our previous studies reveal OB/​200G to exert antiobesity effects in dietary animal models of obesity. AIM OF THE STUDY: The present study investigated the possible involvement of serotonergic system in the effect of OB/​200G on food intake. We examined the effects of systemic pretreatment with 5/​HT depletor, p/​chlorophenylalanine (PCPA, 300 mg/kg, i. p. for 6 days), 5/​HT1A agonist, (8/​hydroxy/​2/​(di/​N/​propylamino)/​tetralin (8/​OH/​DPAT, 0.1 mg/kg, i. p.), nonselective 5/​HT antagonist, cyproheptadine (1 mg/kg, i. p.), 5/​HT2 receptor antagonist, seganserin (1 and 2 mg/kg, i. p.) and 2/​deoxy/​D/​glucose (2/​DG, glucose antimetabolite, 500 mg/kg, i. p.) on satiety induced by OB/​200G (500 mg/kg, p. o.) in non/​deprived female mice. The results were compared with fluoxetine (10 mg/kg, i. p.), a selective serotonin reuptake inhibitor. METHODS: Fifteen minutes after the last drug administration, groups of mice were presented with sweetened chow and the amount of food consumed was recorded at 0.5,1,2, 3 and 4h time intervals. RESULTS: The hyperphagic effect of PCPA, 8/​OH/​DPAT, cyproheptadine and 2/​DG was significantly (p < 0.05) antagonized by both OB/​200G and fluoxetine. However, the anorectic effect of fluoxetine was not reversed by centrally acting 5/​HT2 antagonist, seganserin but the latter markedly attenuated the satiety action of OB/​200G. CONCLUSION: The present observations suggest the role of serotonin in mediation of satiety by OB/​200G and hence its antiobesity effect.

  Publication Types: Comparative Study Research Support, Non/​U.S. Gov't

  PMID: 11697445 [PubMed /​ indexed for MEDLINE]

  
  

  27: Bioorg Med Chem Lett. 2001 Apr 23;11(8):985/​9.

  New triterpenes, myrrhanol A and myrrhanone A, from guggul/​gum resins, and their potent anti/​inflammatory effect on adjuvant/​induced air/​pouch granuloma of mice.

  Kimura I, Yoshikawa M, Kobayashi S, Sugihara Y, Suzuki M, Oominami H, Murakami T, Matsuda H, Doiphode VV.

  Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan. ikukokim@ms.toyama/​mpu.ac.jp

  Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)/​gum resin, displays a potent anti/​inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant/​induced air/​pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a potent anti/​inflammatory agent.

  Publication Types: Comparative Study

  PMID: 11327606 [PubMed /​ indexed for MEDLINE]

  
  

  28: Altern Ther Health Med. 2001 Mar;7(2):120, 112/​4.

  Usefulness of guggul (Commiphora mukul) for osteoarthritis of the knee: An experimental case study.

  Singh BB, Mishra L, Aquilina N, Kohlbeck F.

  Southern California University of Health Sciences (SCUHS), Whittier, Calif., USA.

  Publication Types: Case Reports

  PMID: 11253408 [PubMed /​ indexed for MEDLINE]

  
  

  29: J AOAC Int. 2001 Jan/​Feb;84(1):24/​8.

  Simultaneous determination of E/​ and Z/​guggulsterones in dietary supplements containing Commiphora mukul extract (guggulipid) by liquid chromatography.

  Nagarajan M, Waszkuc TW, Sun J.

  Enzymatic Therapy, Green Bay, WI 54311, USA.

  Guggulipid, the standardized product from the extraction of the ole/​gum/​resin from the Commiphora mukul plant, has been marketed as a hypolipidemic agent. The ketosteroids, cis/​ and trans/​4,17(20)/​pregnadiene/​3,16/​dione, known as E/​ and Z/​guggulsterones, respectively, are the main ingredients in guggulipid. A liquid chromatographic method was developed for simultaneous determination of E/​ and Z/​guggulsterones in guggulipid preparations using synthetic E/​ and Z/​guggulsterone standards. Realtively low amounts of guggulsterones (E and Z) were found in commercial guggulipid preparations in comparison with the manufacturer's claim of 2.5%. The mixture of E/​ and Z/​guggulsterones was extracted and separated on a Symmetry C18 reversed/​phase column, with a mobile phase of acetonitrile/​/​water (46 + 54, v/v) and detected at 242 nm. The retention times of E/​ and Z/​guggulsterones are approximately 8 and 11 min, respectively. Assay quantitation was based on the calibration curve obtained from a mixture of synthetic standard E/​ and Z/​guggulsterones. Experimental data on selectivity, linearity, accuracy, and recoveries are presented.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 11234828 [PubMed /​ indexed for MEDLINE]

  
  

  30: Life Sci. 1999;65(12):PL137/​41.

  Gugulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation.

  Panda S, Kar A.

  School of Life Sciences, Devi Ahilya University, Vigyan Bhawan, Indore, India.

  An investigation was made to find out the importance of gugulu (Commiphora mukul) in thyroid function of mice and to reveal the possible involvement of lipid peroxidation (LPO), if any. While no marked change in the concentrations of serum thyroxine (T4) was observed, triiodoth yronine (T3) concentration and T3/T4 ratio were enhanced following the administration of gugulu extract (0.2 g/kg b. wt./d for 15 days). A concomitant decrease in LPO was also noticed in liver, the principal site of T3 generation, suggesting that gugulu induced increase in T3 concentration is LPO mediated.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 10503949 [PubMed /​ indexed for MEDLINE]

  
  

  31: J Chromatogr B Biomed Sci Appl. 1998 Dec 11;720(1/​2):189/​96.

  High/​performance liquid chromatographic method for fingerprinting and quantitative determination of E/​ and Z/​guggulsterones in Commiphora mukul resin and its products.

  Mesrob B, Nesbitt C, Misra R, Pandey RC.

  Xechem, Inc., Research Laboratories, New Brunswick, NJ 08901, USA.

  A high/​performance liquid chromatographic method has been developed and validated for the fingerprinting (profiling) and quantitative determination of E/​ and Z/​guggulsterones, the hypolipidemic agents in the gum/​resin exudate of Commiphora mukul, currently marketed worldwide as hypocholesterolemic. The method involves extraction of the guggul/​resin from either the raw exudate or compounded tablets (or capsules) with ethyl acetate, concentration of the combined extracts and chromatography on a reversed/​phase C18 column using an acetonitrile/​water gradient. The method has a validated quantitation range of 15/​85 microg/ml for E/​guggulsterone and 25/​130 microg/ml for Z/​guggulsterone with a precision of +//​2% S.D. and a recovery of >99.5%. Standard curve correlation coefficients of 0.992 or greater were obtained during validation experiments. The method was applied to six commercial (OTC) products, all of which were found to contain significantly less (in most cases very little or none) of the claimed guggulsterones.

  PMID: 9892081 [PubMed /​ indexed for MEDLINE]

  
  

  32: Altern Med Rev. 1998 Dec;3(6):422/​31.

  Botanical influences on cardiovascular disease.

  Miller AL.

  Alternative Medicine Review. P.O. Box 25, Dover, ID 83825, USA. alan@thorne.com

  Several botanicals, including Crataegus oxycantha, Terminalia arjuna, Inula racemosa, and Astragalus membranaceus, have been found to have therapeutic benefit for the treatment of cardiovascular disease. Crataegus oxycantha has been used traditionally as a cardiac tonic and current uses include treatment for angina, hypertension, arrhythmias, and congestive heart failure. Animal studies have also indicated that Crataegus extracts may also have potential use as anti/​ischemic and lipid/​lowering agents. The bark of the Terminalia arjuna tree has a long history of use as a cardiac tonic as well, and has been indicated in the treatment of coronary artery disease, heart failure, hypercholesterolemia and for relief of anginal pain. Additionally, it has been found to have antibacterial and antimutagenic properties. Inula racemosa, also known as Pushkarmoola, is another traditional Ayurvedic botanical that has potential cardioprotective benefit. In human trials, a combination of Inula racemosa and Commiphora mukul was shown to be superior to nitroglycerin in reducing the chest pain and dyspnea associated with angina. Astragalus membranaceus, a Chinese herb, is often used as a "Qi tonifier" and has been studied for its therapeutic benefit in treatment of ischemic heart disease, myocardial infarction, heart failure, and relief of anginal pain. Clinical studies have indicated that its in vitro antioxidant activity is the mechanism by which it affords its cardioprotective benefit.

  Publication Types: Review

  PMID: 9855567 [PubMed /​ indexed for MEDLINE]

  
  

  33: Indian J Physiol Pharmacol. 1998 Jan;42(1):101/​6.

  Role of Lipistat in protection against isoproterenol induced myocardial necrosis in rats: a biochemical and histopathological study.

  Seth SD, Maulik M, Katiyar CK, Maulik SK.

  Department of Pharmacology, All India Institute of Medical Sciences, New Delhi.

  A test drug (Lipistat) comprising of equal/​proportions of extracts of Terminalia arjuna, Inula racemosa Hook, latex of Commiphora mukul, in three different doses (225 mg/kg; 350 mg/kg; 450 mg/kg) were administered orally daily for 6 days a week for 60 days in rats. Thereafter, the rats were subjected to isoproterenol (ISO) induced (85 mg/kg, s.c. for 2 days) myocardial necrosis. Gross and microscopic examinations (histopathology) were done along with estimations of myocardial tissue high energy phosphates (HEP) stores and lactate content. Gross examination showed significant (P < 0.05) cardioprotection in Lipistat treated animals. On microscopic examination no statistically significant reduction in myocardial damage by 350 and 450 mg/kg of Lipistat were observed although loss of myocardial HEP stores and accumulation of lactate were significantly prevented. The results of the present study suggest the potential usefulness of Lipistat in the prevention of ischemic heart disease.

  PMID: 9513800 [PubMed /​ indexed for MEDLINE]

  
  

  34: Cardiovasc Drugs Ther. 1994 Aug;8(4):659/​64.

  Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia.

  Singh RB, Niaz MA, Ghosh S.

  Heart Research Laboratory, Medical Hospital and Research Centre, Moradabad, India.

  The effects of the administration of 50 mg of guggulipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit/​ and vegetable/​enriched prudent diet in the management of 61 patients with hypercholesterolemia (31 in the guggulipid group and 30 in the placebo group) in a randomized, double/​blind fashion. Guggulipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the postdiet levels, whereas the levels were unchanged in the placebo group. The HDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The compliance of patients was greater than 96%. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid/​lowering effect of modern drugs. After a washout period of another 12 weeks, changes in blood lipoproteins were reversed in the guggulipid group without such changes in the placebo group. Side effects of guggulipid were headache, mild nausea, eructation, and hiccup in a few patients.

  Publication Types: Clinical Trial Comparative Study Randomized Controlled Trial

  PMID: 7848901 [PubMed /​ indexed for MEDLINE]

  
  

  35: Planta Med. 1993 Feb;59(1):12/​6.

  Anti/​inflammatory activity of resins from some species of the plant family Burseraceae.

  Duwiejua M, Zeitlin IJ, Waterman PG, Chapman J, Mhango GJ, Provan GJ.

  Department of Physiology and Pharmacology, Royal College, University of Strathclyde, Glasgow, Scotland.

  The anti/​inflammatory activities of extracts from the resins of four species of the plant family Burseraceae, Boswellia dalzielli, Boswellia carteri (gum olibanum), Commiphora mukul, and Commiphora incisa, were studied. The aqueous extracts of the resins of B. dalzielli, C. incisa, and C. mukul significantly inhibited both the maximal edema response and the total edema response during 6 h of carrageenan/​induced rat paw edema. The octanordammarane triterpenes, mansumbinone and mansumbinoic acid, isolated from the resin of C. incisa, were separated and tested. Administered prophylactically, mansumbinone proved to be more than 20 times less potent than indomethacin and prednisolone in inhibiting carrageenan/​induced rat paw edema. However, the molar potency of mansumbinoic acid was within one order of magnitude of those of indomethacin and prednisolone. The anti/​inflammatory action of the acid on the carrageenan/​induced edema was dose/​related between 1.3 x 10(/​5) and 2.5 x 10(/​4) mol kg/​1 when given before the inflammatory stimulus. The acid was able to reverse an established carrageenan/​induced inflammatory response when administered 2 h after induction. Daily administration of mansumbinoic acid at a single dose level (1.5 x 10(/​4) mol kg/​1) significantly reduced joint swelling in adjuvant arthritis in rats. The results indicated that this compound is worthy of further investigation as an anti/​inflammatory drug.

  Publication Types: Research Support, Non/​U.S. Gov't

  PMID: 8441773 [PubMed /​ indexed for MEDLINE]

  
  

  36: J Postgrad Med. 1991 Jul;37(3):132/​5.

  Beneficial effects of Allium sativum, Allium cepa and Commiphora mukul on experimental hyperlipidemia and atherosclerosis/​/​a comparative evaluation.

  Lata S, Saxena KK, Bhasin V, Saxena RS, Kumar A, Srivastava VK.

  Department of Pharmacology, L. L. R. M. Medical College, Meerut, Uttar Pradesh.

  Oral administration of petroleum ether extract of Allium sativum, Allium cepa and ethylacetate extract of Commiphora mukul in albino rats significantly prevented rise in serum cholesterol and serum triglyceride level, caused by atherogenic diet. All the three agents were also found to confer significant protection against atherogenic diet induced atherosclerosis.

  Publication Types: Comparative Study

  PMID: 1784023 [PubMed /​ indexed for MEDLINE]

  
  

  37: Indian J Med Res. 1988 Apr;87:356/​60.

  Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL/​cholesterol.

  Verma SK, Bordia A.

  Publication Types: Clinical Trial Randomized Controlled Trial

  PMID: 3169888 [PubMed /​ indexed for MEDLINE]

  
  

  38: Indian J Med Res. 1988 Apr;87:327/​35.

  Gum guggul (Commiphora mukul)/​/​the success story of an ancient insight leading to a modern discovery.

  Satyavati GV.

  Publication Types: Review

  PMID: 3049326 [PubMed /​ indexed for MEDLINE]

  
  

  39: Planta Med. 1984 Feb;(1):78/​80.

  Thyroid stimulating action of Z/​guggulsterone obtained from Commiphora mukul.

  Tripathi YB, Malhotra OP, Tripathi SN.

  PMID: 6739577 [PubMed /​ indexed for MEDLINE]

  
  

  40: J Assoc Physicians India. 1981 Jan;29(1):13/​7.

  Effects of Commiphora Mukul (Guggul) in experimentally induced hyperlipemia and atherosclerosis.

  Baldwa VS, Bhasin V, Ranka PC, Mathur KM.

  PMID: 7263585 [PubMed /​ indexed for MEDLINE]

  
  

  41: Biochem Exp Biol. 1980;16(4):421/​4.

  Hypolipidemic activity of guggal resin (Commiphora mukul) and garlic (Alium sativum linn.) in dogs (Canis familiaris) and monkeys (Presbytis entellus entellus Dufresne).

  Dixit VP, Joshi S, Sinha R, Bharvava SK, Varma M.

  1. The identification of cholesterol as a constituent in the genesis of coronary artery disease in man and experimental animals are well documented. 2. The hypolipidemic effects of Commiphora mukul (guggulu) and Alium sativum (Garlic powder) were screened in dog and Presbytis monkeys. 3. Progressive decrease in the mean values of cholesterol, triglycerides and phospholipids were conspicuous for forty eight hours following the administration of guggulu/garlic powder. 4. 25 mg/kg body weight garlic powder was more effective in lowering the serum cholesterol and triglycerides as compared with that of guggulu. 5. A comparative hypolipidemic action of the two compounds is discussed.

  Publication Types: Comparative Study Research Support, Non/​U.S. Gov't

  PMID: 7346059 [PubMed /​ indexed for MEDLINE]

  
  

  42: Indian J Exp Biol. 1978 Sep;16(9):1021/​3.

  Effect of oleoresin of gum guggul (Commiphora mukul) on the reproductive organs of female rat.

  Amma MK, Malhotra N, Suri RK, Arya OP, Dani HM, Sareen K.

  PMID: 721150 [PubMed /​ indexed for MEDLINE]

  
  

  43: J Assoc Physicians India. 1978 May;26(5):367/​73.

  Effect of guggulu (Commiphora mukul/​/​Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases.

  Kuppurajan K, Rajagopalan SS, Rao TK, Sitaraman R.

  PMID: 730716 [PubMed /​ indexed for MEDLINE]

  
  

  44: Zentralbl Bakteriol Naturwiss. 1978;133(7/​8):723/​5.

  Efficacy of some essential oils and their constituents on few ubiquitous molds.

  Sarbhoy AK, Varshney JL, Maheshwari ML, Saxena DB.

  Six essential oils of Mentha arvensis, Mentha piperita, Anethum sowa, Cymbopogon winterianus, Nardostachys jatamansi, and Commiphora mukul were selected and tested for their efficacy against Aspergillus flavus, A. fumigatus, A. sulphureus, Mucor fragilis, and Rhizopus stolonifer. These oils were fungistatic or fungicidal to one or the other molds, depending upon the concentrations.

  Publication Types: Comparative Study

  PMID: 749414 [PubMed /​ indexed for MEDLINE]

  
  

  45: Arzneimittelforschung. 1977 Jul;27(7):1455/​7.

  Comparison of the anti/​inflammatory activity of Commiphora mukul (an indigenous drug) with those of phenylbutazone and ibuprofen in experimental arthritis induced by mycobacterial adjuvant.

  Sharma JN, Sharma JN.

  In the present investigation a method of induction of experimental arthritis in animals was modified to provide a better model replica of human arthritis. Inflammatory syndrome, resembling rheumatoid arthritis in man, was induced in the right hock joint of albino rabbits by intra/​articular injection of the killed mycobacterial adjuvant in liquid paraffin. Development of this arthritic syndrome was studied from a period of five months with and without drugs. Anti/​inflammatory agents such as phenylbutazone, ibuprofen and fraction "A" of gum/​guggual from Commiphora mukkul were administered orally at a daily dose of 100, 100 and 500 mg/kg, respectively, for a period of five months. All three drugs decreased the thickness of the joint swelling during the course of drug treatment. These results indicate the beneficial role of phenylbutazone, ibuprofen and fraction "A" of gum/​guggul in experimental arthritis.

  Publication Types: Comparative Study

  PMID: 578471 [PubMed /​ indexed for MEDLINE]

  
  

  46: Indian J Med Res. 1977 Mar;65(3):390/​5.

  Long term clinical studies on the hypolipidaemic effect of Commiphora mukul (Guggulu) and clofibrate.

  Malhotra SC, Ahuja MM, Sundaram KR.

  Publication Types: Comparative Study

  PMID: 924552 [PubMed /​ indexed for MEDLINE]

  
  

  47: Indian J Exp Biol. 1977 Feb;15(2):143/​5.

  Effect of fraction 'A' of Commiphora mukul (Guggulu) on Mongolian gerbils Meriones unguiculatus.

  Ahuja MM, Malhotra SC, Tandon HD.

  PMID: 892883 [PubMed /​ indexed for MEDLINE]

  
  

  48: Indian J Exp Biol. 1973 May;11(3):166/​8.

  Effect of some fractions of Commiphora mukul on various serum lipid levels in hypercholesterolemic chicks and their effectiveness in myocardial infarction in rats.

  Arora RB, Das D, Kapoor SC, Sharma RC.

  Publication Types: Comparative Study

  PMID: 4782614 [PubMed /​ indexed for MEDLINE]

  
  

  49: Arch Pharm (Weinheim). 1972 Jul;305(7):486/​93.

  [Monocyclic diterpenes from Indian gugul resin (Commiphora mukul)]

  [Article in German]

  Rucker G.

  PMID: 5047668 [PubMed /​ indexed for MEDLINE]

  
  

  50: Indian J Med Res. 1972 Jun;60(6):929/​31.

  Anti/​inflammatory studies on a crystalline steroid isolated from Commiphora mukul.

  Arora RB, Taneja V, Sharma RC, Gupta SK.

  Publication Types: Comparative Study

  PMID: 4660307 [PubMed /​ indexed for MEDLINE]

  
  

  51: Indian J Med Res. 1971 Oct;59(10):1621/​32.

  Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction 'A', ethyl/​P/​chlorophenoxyisobutyrate and Ciba/​13437/​Su.

  Malhotra SC, Ahuja MM.

  Publication Types: Comparative Study

  PMID: 5159000 [PubMed /​ indexed for MEDLINE]

  
  

  52: Indian J Exp Biol. 1971 Jul;9(3):403/​4.

  Isolation of a crystalline steroidal compound from Commiphora mukul & its anti/​inflammatory activity.

  Arora RB, Kapoor V, Gupta SK, Sharma RC.

  PMID: 5144347 [PubMed /​ indexed for MEDLINE]

  
  

  53: Indian J Exp Biol. 1971 Jul;9(3):376/​7.

  Hypocholesterolemic effect of Commiphora mukul resin (guggal).

  Nityanand S, Kapoor NK.

  PMID: 5144338 [PubMed /​ indexed for MEDLINE]

  
  

  54: Indian J Med Res. 1969 Oct;57(10):1950/​62.

  Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Engl. (Guggul).

  Satyavati GV, Dwarakanath C, Tripathi SN.

  PMID: 5372181 [PubMed /​ indexed for MEDLINE]

  
  

  55: Indian J Med Res. 1969 May;57(5):900/​6.

  A biochemical approach to anti/​atherosclerotic action of Commiphora/​mukul: an Indian indigenous drug in Indian domestic pigs (Sus scrofa).

  Khanna DS, Agarwal OP, Gupta SK, Arora RB.

  PMID: 5820438 [PubMed /​ indexed for MEDLINE]

  
  

Watch the following videos to gain better understanding of Ayurvedic Medicine and Phytonutrients and the role they play in promoting Prostate Health. Please contact our heath advisors and Ayurvedic doctors with your questions and feedback!

AYURSTATE for Prostate Care (Part 1) - Ayurvedic Medicine, 8 Herbal Extracts, 50 Phytonutrients