Publication Date:
2002-05-04
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- New York, N.Y. -- Science. 2002 May 31;296(5573):1703-6. Epub 2002 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988537" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Binding Sites
;
Caco-2 Cells
;
Carrier Proteins/genetics/metabolism
;
Cells, Cultured
;
Chenodeoxycholic Acid/pharmacology
;
Cholesterol/*metabolism
;
Cholesterol, Dietary/administration & dosage
;
DNA/metabolism
;
DNA-Binding Proteins/*antagonists & inhibitors/chemistry/genetics/*metabolism
;
Hepatocytes/metabolism
;
Histone Acetyltransferases
;
Humans
;
*Hydroxysteroid Dehydrogenases
;
Hypolipidemic Agents/metabolism/*pharmacology
;
Ligands
;
Liver/metabolism
;
*Membrane Glycoproteins
;
Mice
;
Nuclear Receptor Coactivator 1
;
Pregnenediones/metabolism/*pharmacology
;
Promoter Regions, Genetic
;
Protein Structure, Tertiary
;
Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/genetics/metabolism
;
Receptors, Steroid/antagonists & inhibitors/metabolism
;
Transcription Factors/*antagonists & inhibitors/chemistry/genetics/*metabolism
;
Transcriptional Activation/drug effects
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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