Abstract
In this study, we confirmed that ursolic acid, a plant triterpenoid, activates peroxisome proliferator-activated receptor (PPAR)-α in vitro. Surface plasmon resonance and time-resolved fluorescence resonance energy transfer analyses do not show direct binding of ursolic acid to the ligand-binding domain of PPAR-α; however, ursolic acid enhances the binding of PPAR-α to the peroxisome proliferator response element in PPAR-α-responsive genes, alters the expression of key genes in lipid metabolism, significantly reducing intracellular triglyceride and cholesterol concentrations in hepatocytes. Thus, ursolic acid is a PPAR-α agonist that regulates the expression of lipid metabolism genes, but it is not a direct ligand of PPAR-α.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cholesterol / analysis
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Dose-Response Relationship, Drug
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Drug Discovery
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Drug Evaluation, Preclinical
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Fatty Acids / metabolism
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Genes, Reporter
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Hep G2 Cells
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Hepatocytes / metabolism
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Humans
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Hypertriglyceridemia / drug therapy
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Hypertriglyceridemia / physiopathology*
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Hypolipidemic Agents / chemical synthesis*
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Hypolipidemic Agents / chemistry
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Hypolipidemic Agents / pharmacology*
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Lipid Metabolism*
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Liver / metabolism*
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Luciferases / analysis
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Molecular Targeted Therapy
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PPAR alpha / agonists*
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PPAR alpha / genetics
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Peroxisome Proliferators / metabolism
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Phytotherapy
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Protein Binding
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Triglycerides / analysis
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Triterpenes / chemistry
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Triterpenes / pharmacology*
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Ursolic Acid
Substances
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Fatty Acids
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Hypolipidemic Agents
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PPAR alpha
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Peroxisome Proliferators
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Triglycerides
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Triterpenes
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Cholesterol
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Luciferases