Discovery of β-Carboline Derivatives as a Highly Potent Cardioprotectant against Myocardial Ischemia-Reperfusion Injury.

Timely myocardial reperfusion salvages ischemic myocardium from infarction, whereas reperfusion itself induces cardiomyocyte death, which is called myocardial ischemia/reperfusion (MI/R) injury. Herein, β-carboline derivative was designed and synthesized with obvious myocardial protective activity for the first time. Pretreatment of effectively protected the cardiomyocyte H9c2 cells from HO-induced lactate dehydrogenase leakage and restored the endogenous antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Besides, effectively protected the mitochondria through decreasing the reactive oxygen species overproduction and enhancing the mitochondrial membrane potential. As a result, significantly reduced the necrosis of cardiomyocytes in HO-induced oxidative stress, which was more potent than polydatin. In MI/R injury rats, pretreatment obviously increased the levels of SOD and GSH-Px and inhibited the apoptosis of cardiomyocytes. Through this way, the size of myocardial infarction was significantly reduced after MI/R injury , better than that of polydatin, suggesting that is a promising cardioprotectant for the prevention of MI/R injury.