A natural product that lowers cholesterol as an antagonist ligand for FXR.
Article Details
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Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD
A natural product that lowers cholesterol as an antagonist ligand for FXR.
Science. 2002 May 31;296(5573):1703-6. Epub 2002 May 2.
- PubMed ID
- 11988537 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Myrrh Bile acid receptor Protein Humans UnknownAntagonistDetails Myrrh Nuclear receptor subfamily 1 group I member 2 Protein Humans UnknownPartial agonistDetails Myrrh Peroxisome proliferator-activated receptor alpha Protein Humans UnknownAgonistDetails