Experimental Study Of Osthole On Treatment Of Hyperlipidemic Fatty Liver And Its Mechanisms In Rats

Aim: To study the therapeutic effects of osthole on hyperlipidemic fatty liver and investigate the possible mechanisms.Methods: Rat model with hyperlipidemic fatty liver was established by feeding fatty milk for 6 weeks. The experimental rats were then treated with osthole 5-20 mg/kg for 6 weeks. Mouse hyperlipidemic model was induced by feeding fatty milk for 3 weeks when they were treated with osthole 10-40 mg/kg for 3 weeks. The therapeutic and anti-oxidation effects of osthole on hyperlipidemic fatty liver and effects on LPL and HL activities in hyperlipidemic mice were observed, respectively. Expression of PPARα/γmRNA and protein, CYP7A mRNA and protein, DGAT mRNA and protein and L-FABP and FATP4 mRNA in hepatic tissues of hyperlipidemic fatty liver rats was examined by RT-PCR and Western blot methods, respectively.Results: After treatment with osthole 5-20 mg/kg for 6 weeks, the levels of rat serum TC, TG, LDL-C, FFA were significantly decreased as compared with the fatty liver model group (P<0.05 or P<0.01), hepatic weight and its coefficient, the hepatic tissue contents of TC, TG, and MDA were also decreased (P<0.05 or P<0.01), serum HDL-C was significantly increased (P<0.01). In fatty milk-induced hyperlipidemic mice, the post-heparin plasma lipids and activities of LPL and HL were significantly decreased and increased after treatment with osthole 10-20 mg/kg, respectively (P<0.05 or P<0.01). When the dose of osthole added to 40 mg/kg, the post-heparin plasma lipid levels were further decreased, but the activities of LPL and HL were not significantly increased. The histological evaluation of liver specimens demonstrated that osthole dramatically decreased lipid accumulation and improved the ultrastructure of hepatocytes (P<0.05 or P<0.01). Osthole could significantly increase the expression of PPARα/γand CYP7A mRNA and protein and L-FABP and FATP4 mRNA (P<0.05 or P<0.01), decrease the expression of DGAT mRNA and protein in hepatic tissues of hyperlipidemic fatty liver rats (P<0.05 or P<0.01).Conclusion: Osthole had therapeutic effects on fatty milk-induced rat fatty liver, the mechanisms might be associated with its anti-oxidation and the elevation of the LPL and HL activities, and regulation of the mRNA and protein expression of CYP7A, DGAT, and the mRNA expression of L-FABP and FATP4 via increasing PPARα/γmRNA and protein expression.