Journal
SCIENCE
Volume 296, Issue 5573, Pages 1703-1706Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1072891
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Extracts of the resin of the guggul tree (Commiphora mukul) tower LDL (low-density lipoprotein) cholesterol levels in humans. The plant sterol guggul-sterone [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.
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