Ginsenoside Rc Alleviates Myocardial Ischemia-Reperfusion Injury by Reducing Mitochondrial Oxidative Stress and Apoptosis: Role of SIRT1 Activation

Abstract

Myocardial ischemia-reperfusion (MI/R) injury occurs when coronary blood supply is impaired and then re-established, leading to additional injury to the myocardial tissue, including mitochondria oxidative stress and apoptosis. Ginsenoside Rc is one of the main protopanaxadiol-type saponins, and there has been relatively little research on it. Despite research confirming that ginsenoside Rc regulates mitochondrial functions, its potential benefits against MI/R injury have not been explored. In this study, we examined the protective effects of ginsenoside Rc in MI/R injury, along with its underlying mechanisms, using an in vitro H9c2 cell model of oxygen–glucose deprivation/reoxygenation (OGD/R) and an in vivo rat model of MI/R injury. Prior to this, the H9c2 cells or rats were exposed to ginsenoside Rc with or without SIRT1 small interfering RNA (siRNA) or the selective SIRT1 inhibitor EX527. The results showed that after MI/R (or OGD/R) injury, ginsenoside Rc had a cardioprotective effect; improved cardiac function (or cell survival); reduced myocardial infarct size; decreased levels of creatine kinase-MB, cardiac troponin I, and lactate dehydrogenase (LDH) in the serum (or LDH release into culture medium); reduced cardiomyocyte apoptosis; and attenuated mitochondrial oxidative damage. Ginsenoside Rc pre-treatment also upregulated the anti-apoptotic protein Bcl-2 while downregulating the pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the cardioprotective effect of ginsenoside Rc was concomitant with upregulated SIRT1 expression and downregulated Ac-FOXO1 expression. SIRT1 siRNA or SIRT1 inhibitor EX527 abolished the cardioprotective effects of ginsenoside Rc by inhibiting the SIRT1 signaling pathway. In conclusion, our findings demonstrate that ginsenoside Rc ameliorated MI/R injury by reducing mitochondrial oxidative stress and apoptosis, at least in part, by activating SIRT1.