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Planta Med 2007; 73(8): 718-724
DOI: 10.1055/s-2007-981552
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Osthole Improves Fat Milk-Induced Fatty Liver in Rats: Modulation of Hepatic PPAR-alpha/gamma-Mediated Lipogenic Gene Expression

Yan Zhang1 , Meilin Xie1 , Jie Xue1 , Zhenlun Gu1
  • 1Department of Pharmacology, Medical School of Soochow University, Suzhou, P.R. China
Further Information

Publication History

Received: November 7, 2006 Revised: May 15, 2007

Accepted: May 23, 2007

Publication Date:
05 July 2007 (online)

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Abstract

The objectives of this study were to determine the therapeutic effect of osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), in hyperlipidemic fatty liver (HFL) rats and investigate the possible mechanism of the osthole treatment. The HFL rat model was established by feeding Sprague-Dawley rats with fat milk for 6 weeks. The experimental rats were then treated with a dose of osthole of 5 - 20 mg/kg for 6 weeks. After the treatment, total cholesterol (TC) and triglycerides (TG) in serum and hepatic tissue, as well as the coefficient of hepatic weight were measured. The results showed that the TC and TG in both serum and hepatic tissue and the coefficient of hepatic weight in the osthole-treated rats were lower as compared to those in the experimental group, respectively (P < 0.05 or P < 0.01). Moreover, as compared to the control group, the osthole treatment increased the PPARα/γ mRNA expression by 58.0 - 84.0 % and 20.4 - 77.4 %, respectively. The related target genes for mRNA expression were also increased by osthole-treatment, e. g., 53.4 - 93.2 % for CYP7A, 21.1 - 63.2 % for L-FABP and 34.1 - 57.3 % for FATP4, while the DGAT mRNA expression was decreased by 26.0 - 44.4 %. The therapeutic effect of osthole was further confirmed by histological evaluation of the liver showing a dramatically decreased lipid accumulation and improved ultrastructure of hepatocytes. In conclusion, osthole exerts therapeutic effects on fat milk-induced fatty liver in rats, by regulating mRNA expression of the target genes of CYP7A, DGAT, L-FABP and FATP4 via increasing the PPARα/γ mRNA expression.

Key words

Cnidium monnieri (L.) Cusson - Apiaceae - osthole - fatty liver - PPARα/γ - lipid metabolism

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Dr Meilin Xie

Department of Pharmacology

Medical School of Soochow University

Suzhou 215123

People's Republic of China

Phone: +86-512-6588-0320

Email: Xiemeilin@suda.edu.cn