Cholesterol Metabolism

Folk Medicine Meets Nuclear Receptors

Science's STKE  04 Jun 2002:
Vol. 2002, Issue 135, pp. tw201-TW201
DOI: 10.1126/stke.2002.135.tw201

The gum resin of the guggul tree Commiphora mukul has been used in Ayurvedic medicine since 600 B.C. to treat a wide variety of ailments, including obesity and lipid disorders. Although not well known in Western medicine, an extract of this resin (guggulipid) is clinically approved and widely used in India as a cholesterol-lowering agent. Urizar et al. show that guggulsterone, the active agent in this extract, is a potent antagonist ligand for the nuclear hormone receptor FXR. As the primary bile acid sensor, FXR plays a central role in cholesterol metabolism; thus, this antagonist function is likely to be the molecular basis for guggulsterone's lipid-lowering activity. These results raise the exciting possibility that FXR and other nuclear hormone receptors may mediate the effects of other biologically active natural products that could provide new leads for drug development.

N. L. Urizar, A. B. Liverman, D. T. Dodds, F. V. Silva, P. Ordentlich, Y. Yan, F. J. Gonzalez, R. A. Heyman, D. J. Mangelsdorf, D. D. Moore, A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296, 1703-1706 (2002) [Abstract] [Full Text]