Rosa rugosa flavonoids exhibited PPARα agonist-like effects on genetic severe hypertriglyceridemia of mice

Ethnopharmacological relevance: Rosa rugosa Thunb. is a traditional Chinese medicine that was used in the treatment of cardiovascular diseases and relative risk factors such as diabetes, hyperlipidemia, hypertension, and inflammation. Rosa rugosa flavonoids (RRFs) are the main components in Rosa rugosa Thunb. Several studies have demonstrated that RRFs can regulate plasma lipid contents, but the related mechanism of which has not yet been elucidated clearly. Aim of the study: The goal of this study was to clarify the effects of RRFs on triglyceride metabolism and its related mechanisms. Materials and methods: RRFs were obtained by ethanol extraction from Rosa rugosa Thunb.. Transgenic mice expressing human Apolipoprotein C3 (ApoC3) were used as a mouse model of hypertriglyceridemia. Fenofibrate (FNB), a PPARa agonist, was used as a positive control drug of decreasing high triglyceride. FNB (100 mg/kg) or RRFs (300 mg/kg) were given to the mice by gavage daily. Two weeks later, the changes of plasma lipid levels in the mice were measured by commercial kits, the clearance of triglyceride was evaluated by oral fat load test, and expression of the genes related to lipid beta-oxidation and synthesis was detected in the mice livers by real time PCR. Results: RRFs, as well as FNB, were found to significantly reduce plasma triglyceride (TG) levels in ApoC3 transgenic mice after administration of the drug for two weeks. Plasma lipid clearance rate was increased and lipid content in the mice livers was reduced after administration of RRF. Treatment with RRFs up-regulated mRNA expression of PPARa and its downstream gene of ACOX, while down-regulated mRNA expression of the genes related to fatty acid synthesis (FASN, SREBP-1c, and ACC1). The expression of LPL was raised, while the expression of ApoC3 was decreased, and Foxo1 was inhibited by RRFs in the mice livers. Conclusion: RRFs can reduce plasma TG levels by repressing the expression of ApoC3 and inducing the expression of LPL in liver. RRFs could also reduce triglyceride in hepatocytes through increasing beta-oxidation and decreasing synthesis of the lipids. These findings show the potency of further clinical application of RRFs as a hypolipidemic drug for treatment of cardiovascular diseases.