A natural product that lowers cholesterol as an antagonist ligand for FXR |
| |
Authors: | Urizar Nancy L Liverman Amy B Dodds D'Nette T Silva Frank Valentin Ordentlich Peter Yan Yingzhuo Gonzalez Frank J Heyman Richard A Mangelsdorf David J Moore David D |
| |
Affiliation: | Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|