Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK.

OBJECTIVE: Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated. METHODS: Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days. Then MIRI was induced by 45 minutes coronary artery ligation and 3 hours reperfusion. Myocardial infarct size (MIS) and histopathology, activities of myocardial enzymes, and effects of RRF on inflammation and apoptosis were evaluated. RESULTS: Pretreating the mice with RRF significantly reduced MIS and inhibited activity of plasma myocardial enzymes. Activity of the enzymes associated with anti-oxidation, SOD, and TEAC, and mRNA expression of NOX2 were significantly elevated. RRF pretreatment significantly decreased the translocation of p65 from the cytoplasm into the nucleus and reduced the expression of the pro-inflammatory cytokines, IL-6 and IL-1ß. RRF pretreatment also significantly prevented the expression of caspase-3 and Bax, and increased the expression of Bcl-2. And RRF inhibited the phosphorylation of JNK and p38 MAPK. CONCLUSIONS: RRF significantly inhibited MIRI through anti-oxidative, anti-inflammatory, and anti-apoptosis effects, and mechanisms were associated with its inhibition on phosphorylation of JNK and p38 MAPK.

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 PPARα 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 ß-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 PPARα 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 ß-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.