Abstract: Objectives Obese patients with type 2 diabetes mellitus (T2DM), which is characterized by hyperglycemia, are liable to more severe myocardial infarction. Semen Cassiae is proved to reduce serum lipid levels. This study was to investigate whether the Semen Cassiae extract (SCE) reduces myocardial ischemia and reperfusion (MI/R) injury with or without diabetes, and the underlying mechanisms. Methods The high-fat diet-fed streptozotocin (HFD-STZ) rat model was created as T2DM model. Normal and DM rats received SCE treatment orally (10 mg/kg/day) for 1 week. Subsequently these animals were subjected to MI/R. Results Compared with the normal animals, DM rats showed increased plasma total cholesterol (TC) and triacylglycerol (TG), and more severe MI/R injury and cardiac functional impairment. SCE treatment significantly reduced the plasma TC and TG, improved the instantaneous first derivation of left ventricle pressure and reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase levels, and apoptosis index at the end of reperfusion in diabetic rats. Moreover, SCE treatment increased the antiapoptotic protein Akt and ERK1/2 phosphorylation levels. Pretreatment with a PI3K inhibitor wortmannin or an ERK1/2 inhibitor PD98059 not only blocked Akt and ERK1/2 phosphorylation respectively, but also inhibited the cardioprotective effects of SCE. However, SCE treatment did not show any effects on the MI/R injury in the normal rats. Conclusion Our data suggest that SCE effectively improves myocardial function and reduces MI/R-induced injury in diabetic but not normal animals, which is possibly attributed to the reduced TC/TG levels and the triggered cell survival signaling Akt and ERK1/2.

Key words: Semen Cassiae, Myocardial ischemia/reperfusion injury, Diabetes, Akt, ERK1/2