Gum guggul and its constituents are increasingly being used as dietary supplements. Biological effects have been demonstrated on lipid metabolism, thyroid hormone homeostatsis, female reproductive tissues, and endogenous nuclear hormone receptors. Gum guggul is the oleoresin of Commiphora mukul, a plant that is native to India, and its extracts include compounds known for their hypolipidemic properties—the Z-and E-isomers of guggulsterone and its related guggulsterols. C. mukul has been used as an inactive pharmaceutical ingredient, binding agent, anti-obesity agent, and cholesterol-reducing agent. Gum guggul is used in incense, lacquers, varnishes, and ointments, as a fixative in perfumes, and in medicine. Therapeutic uses include treatment of nervous diseases, leprosy, muscle spasms, ophthalmia, skin disorders, ulcerative pharyngitis, hypertension, ischaemia, and urinary disorders. Clinical studies of guggul have reported it has cholesterol-reducing effects, however, the first randomized controlled clinical trial of guggulipid done outside of India, reported that standardized doses failed to decrease the levels of low-density lipoprotein cholesterol in healthy adults with hyperlipidemia. Products containing gum guggul or its constituents which are marketed as dietary supplements must adhere to the Federal Food, Drug, and Cosmetic Act. Human exposure to gum guggul most often occurs from ingesting herbal remedies or pharmaceuticals and from the use of cosmetics. Side effects include skin rashes, irregular menstruation, diarrhea, headache, mild nausea, and with very high doses, liver toxicity. In mice, gum guggul extract significantly increased serum triiodothyronine and decreased hepatic lipid peroxidation. In rats, gum guggul and its acid fraction caused significant increases in absolute and relative weights of the ovaries, uterus, and cervix. Gugulipid® significantly increased the levels of catecholamine and the activity of dopamine β-hydroxylase in normal rabbits and decreased those in cholesterol-fed rabbits. It contributed to increasing the levels of catecholamine in hypercholesteremic rabbits and norephinephrine, dopamine, and dopamine β-hydroxylase activity in the heart and brain tissues of rhesus monkeys.
Gum Guggul and Some of Its Steroidal Constituents - Review of Toxicological Literature, Scott A. Masten, Ph.D

Abstract An open comparative trial was conducted in 58 adult obese patients (Body Mass Index min 25 kg/square metre). GroupI1 (n= 27), non-drug, was advised diet (1200-1600 cals) and a brisk walk for 30 minutes. Group II, in addition, received Guggulu (Medohar) 1.5-3 gms/day for 30 days. Mean difference in weight loss between Guggulu and non-drug group was 0.32 kg (ns) on day 15 and 0.58 kg on day 30 (ns). The mean weight reduction in patients ( min 90 kg) was 1.92 kg (ns) and 2.25 kg (ns) higher in Guggulu group. All patients weighing min 90 kg lost weight in Guggulu group whilst 3 in non-drug group did not lose weight. Guggulu was tolerated well. The data from this pilot study suggest a synergistic diet-Guggulu interaction over 30 days in patients weighing min 90 kg which needs to be confirmed in a large placebo controlled study. (J Postgrad Med 1995; 41(1):5-7).
Key Words: Obesity Guggulu, Clinical trial, Diet-drug interaction.
Conceptual and Methodologic challenges of assessing the short-term Efficacy of Guggulu in Obesity: Data Emergent from a Naturalistic Clinical Trial, Bhatt AD, Dalal DG, Shah SJ, Joshi BA, Gajjar MN, Vaidya RA, Vaidya AB, Antarkar DS

Abstract 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 FXR, which is an important regulator of cholesterol homeostasis. It is likely that this effect accounts for the hypolipidemic activity of these phytosteroids.
Summary : More than 40 years ago, Dr. G.V. Satyavati was prompted by an ancient Ayurvedic text to test the effects of the resin of the Commiphora mukul tree on lipid levels. Following her studies, a wide range of efforts have confirmed the hypolipidemic effects of gum guggul and identified guggulsterones as the active agents. It is likely that the function of these compounds as antagonists for the bile acid receptor FXR is the molecular basis for these hypolipidemic effects.
Gugulipid: A Natural Cholesterol-Lowering Agent / AR Reviex in advance 1146, Annu. Rev. Nutr. 2003. 23:303–13

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.
Guggul potentially ameliorates hypothyroidism in female mice, Sunanda Panda and Anand Kar, Phytother. Res. 19, 78–80 (2005)

The mukul myrrh tree (Commiphora mukul), a native of India, secretes the substance guggul (also known as guggulu or guggulipid) when its bark is injured. Guggul has been used in Ayurvedic medicine for thousands of years to treat arthritis and obesity. Guggul extracts were first used in Asia to help manage cholesterol levels and are becoming increasingly popular in the United States. It is believed that guggul can reduce total cholesterol, lowdensity- lipoprotein (LDL) cholesterol, and triglycerides.
Uses. Guggul is promoted as a traditional Ayurvedic treatment for osteoarthritis and obesity. It has also been used for cholesterol management and for skin disorders, specifically nodulocystic acne
Guggul for hypercholesterolemia / studies published in AMJ Health Syst, vol 62

Abstract
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.
(...to be continued)
A natural product that lowers cholesterol as an antagonist ligand for FXR Nancy L Urizar 1, Amy B Liverman, D'Nette T Dodds, Frank Valentin Silva, Peter Ordentlich, Yingzhuo Yan, Frank J Gonzalez, Richard A Heyman, David J Mangelsdorf, David D Moore. PMID: 11988537 DOI: 10.1126/science.1072891

Abstract : Oleo gum resin secreted by Commiphora wightii (A.) Bhandari known as guggul, one of the most reputed drugs in Ayurveda has been extensively studied for its medicinal applications. The plant contains essential oil, mainly consisting of myrecene, dimyrecene and polymyrecene, Z-gugglusterone, E-gugglusterone, gugglusterone-I, gugglusterone-II, and gugglusterone-III. These isolates have been found useful in curing many diseases like rheumatism, arthritis, hyperlipidemia, obesity, inflammation, atherosclerosis, wrinkles, acne and other diseases. The review discusses chemistry and pharmacological activity of guggul
The plant contains essential oil, mainly consisting of myrecene, dimyrecene and polymyrecene, Z-gugglusterone, E-gugglusterone, gugglusterone-I, gugglusterone-II, and gugglusterone- III. These isolates have been found useful in curing many diseases like rheumatism, arthritis, hyperlipidemia, obesity, inflammation, atherosclerosis, wrinkles, and acne.
Key Words: Chemistry, Guggul, Guggulipid, Gugglusterone, Pharmacology, Obesity, Oleo gum resin, Review, Rheumatism
Chemistry and pharmacological profile of guggul - A review, Jain Anurekha, Gupta V B, Indian Journal of Traditional Knowledge Vol. 5(4), October 2006, pp. 478-483