Gum Guggul and Some of Its Steroidal Constituents Review of Toxicological Literature

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 Zand Eisomers 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.