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Text
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URL Address
<a href="http://doi.org/10.1016/s0006-291x(03)00551-5" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/s0006-291x(03)00551-5</a>
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Pages
191-195
Issue
1
Volume
304
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Title
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Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7 alpha-hydroxylase gene
Publisher
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Biochemical and Biophysical Research Communications
Date
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2003
2003-04
Subject
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acid receptor; bile acid; bile-acid synthesis; Biochemistry & Molecular Biology; Biophysics; cholesterol metabolism; feedback-regulation; fxr; liver; natural product; nuclear receptor; nuclear receptors; pregnane X receptor; transport
Creator
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Owsley E; Chiang J Y L
Description
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Bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces bile salt export pump (BSEP) but inhibits cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription in the liver. Guggulsterone, a plant sterol that lowers serum cholesterol, has been shown to antagonize FXR activated genes. Transient transfection assay of a human BSEP/luciferase reporter in HepG2 cells transfected with FXR reveals that guggulsterone strongly antagonizes bile acid induction of the BSEP gene. On the other hand, guggulsterone has no effect on FXR inhibition of the CYP7A1 gene, but strongly inhibits the human CYP7A1 gene by activation of pregnane X receptor (PXR). These results suggest that guggulsterone inhibits bile acid secretion from hepatocytes into bile and activates PXR to inhibit bile acid synthesis in the liver. Reduced conversion of cholesterol and bile acid excretion may lead to an increase of hepatic cholesterol and decrease of intestinal cholesterol absorption, and results in lowering serum cholesterol. (C) 2003 Elsevier Science (USA). All rights reserved.
Identifier
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<a href="http://doi.org/10.1016/s0006-291x(03)00551-5" target="_blank" rel="noreferrer noopener">10.1016/s0006-291x(03)00551-5</a>
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Journal Article
2003
acid receptor
bile acid
bile-acid synthesis
Biochemical and biophysical research communications
Biochemistry & Molecular Biology
Biophysics
Chiang J Y L
cholesterol metabolism
feedback-regulation
FXR
Journal Article
Liver
natural product
Nuclear Receptor
Nuclear Receptors
Owsley E
Pregnane X Receptor
transport