A natural product that lowers cholesterol as an antagonist ligand for FXR.

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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

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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

Myrrh

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Myrrh	Bile acid receptor	Protein	Humans	Unknown	Antagonist	Details
Myrrh	Nuclear receptor subfamily 1 group I member 2	Protein	Humans	Unknown	Partial agonist	Details
Myrrh	Peroxisome proliferator-activated receptor alpha	Protein	Humans	Unknown	Agonist	Details