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
PPARalpha/gamma
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
PPARalpha/gamma
mRNA expression.