Osthol regulates hepatic PPAR alpha-mediated lipogenic gene expression in alcoholic fatty liver murine.
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.
Sun
Fan
F
Department of Pharmacology, Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China.
Xie
Mei-lin
ML
Xue
Jie
J
Wang
Heng-bin
HB
D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D031048:Cnidium / Q000737:chemistry*; D003374:Coumarins / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005638:Fruit; D015870:Gene Expression / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003374:Coumarins; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D012333:RNA, Messenger; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D051048:Diacylglycerol O-Acyltransferase; C046627:osthol