Maslinic Acid Inhibits Myocardial Ischemia-Reperfusion Injury-Induced Apoptosis and Necroptosis via Promoting Autophagic Flux

Apoptosis, necroptosis, and autophagy are the major programmed cell death in myocardial ischemia-reperfusion injury (MIRI). Maslinic acid (MA) has been found to regulate pathophysiological processes that mediate programmed cell death in MIRI, such as inflammation and oxidative stress. However, its effects on MIRI remain unclear. This study intends to explore the role of MA in MIRI. In vitro, MA had no obvious cytotoxic effects on H9C2 cells, and significantly improved the impaired cell viability caused by hypoxia reoxygenation (HR). In vivo, MA significantly alleviated ischemia reperfusion (IR)-induced left ventricular myocardial tissue injury, downregulated creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) levels in serum as well as reducing infarct size. Moreover, MA inhibited HR-induced mitochondrial apoptosis and necroptosis in vitro and in vivo. Of interest, MA interacts with lysosome-associated membrane protein 2 (LAMP2). MA protected LAMP2 from IR and promoting autophagic flux to inhibit apoptosis and necroptosis, whereas these effects were reversed by co-treatment with lysosomal inhibitor BarfA1. In conclusion, MA can inhibit MIRI-induced apoptosis and necroptosis by promoting autophagic flux. These results support that MA is a potential agent to ameliorate MIRI.

Automated summary

The study found that maslinic acid (MA) can inhibit cell death caused by myocardial ischemia-reperfusion injury (MIRI) by promoting autophagic flux. MA can improve tissue damage caused by MIRI, reduce lactate dehydrogenase and creatine kinase-myocardial band levels in serum.