| Osthol regulates hepatic PPAR alpha-mediated lipogenic gene expression in alcoholic fatty liver murine. | |
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MedLine Citation:
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PMID: 20042322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our previous studies found that osthol, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), could ameliorate the accumulation of lipids and decrease the lipid levels in serum and hepatic tissue in alcohol-induced fatty liver mice and rats. The objective of this study was to investigate its possible mechanism of the lipid-lowering effect. A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthol 10, 20, 40 mg/kg for 4 weeks. The BRL cells (rat hepatocyte line) were cultured and treated with osthol at 25, 50, 100, 200 microg/ml for 24h. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) alpha, diacylglycerol acyltransferase (DGAT), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase (CYP7A) in mouse hepatic tissue or cultured hepatocytes were determined by reverse transcription polymerase chain reaction (RT-PCR). After treatment with osthol, the PPAR alpha mRNA expression in mouse liver and cultured hepatocytes was increased in dose dependent manner, while its related target genes for mRNA expression, e.g., DGAT and HMG-CoA reductase, were decreased, the CYP7A was inversely increased. And osthol-regulated mRNA expressions of DGAT, HMG-CoA reductase and CYP7A in the cultured hepatocytes were abrogated after pretreatment with specific inhibitor of PPAR alpha, MK886. It was concluded that osthol might regulate the gene expressions of DGAT, HMG-CoA reductase and CYP7A via increasing the PPAR alpha mRNA expression. |
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Authors:
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Fan Sun; Mei-lin Xie; Jie Xue; Heng-bin Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-29 |
Journal Detail:
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Title: Phytomedicine : international journal of phytotherapy and phytopharmacology Volume: 17 ISSN: 1618-095X ISO Abbreviation: Phytomedicine Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-24 Completed Date: 2010-12-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9438794 Medline TA: Phytomedicine Country: Germany |
Other Details:
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Languages: eng Pagination: 669-73 Citation Subset: IM |
Copyright Information:
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(c) 2009 Elsevier GmbH. All rights reserved. |
Affiliation:
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Department of Pharmacology, Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol 7-alpha-Hydroxylase / genetics, metabolism Cnidium / chemistry* Coumarins / pharmacology* Diacylglycerol O-Acyltransferase / genetics, metabolism Disease Models, Animal Dose-Response Relationship, Drug Fatty Liver, Alcoholic / drug therapy, genetics, metabolism* Fruit Gene Expression / drug effects* Hepatocytes / drug effects, metabolism Hydroxymethylglutaryl CoA Reductases / genetics, metabolism Hypolipidemic Agents / pharmacology* Liver / drug effects*, metabolism, pathology Male Mice Mice, Inbred Strains PPAR alpha / genetics, metabolism* Phytotherapy RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Coumarins; 0/Hypolipidemic Agents; 0/PPAR alpha; 0/RNA, Messenger; 484-12-8/osthol; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 2.3.1.20/Diacylglycerol O-Acyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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