Asiaticoside attenuates oxygen-glucose deprivation/reoxygenation-caused injury of cardiomyocytes by inhibiting autophagy.

ABSTRACT

Asiaticoside is a natural triterpene compound derived from Centella asiatica, possessing confirmed cardioprotective property. However, the roles of asiaticoside in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-caused cardiomyocyte dysfunction remain largely obscure. Human cardiomyocyte AC16 cells were stimulated with OGD/R to mimic myocardial ischemia/reperfusion injury and treated with asiaticoside. Cytotoxicity was investigated by CCK-8 assay and lactate dehydrogenase (LDH) release analysis. Autophagy- and Wnt/ß-catenin signaling-related protein levels were measured via western blotting. Asiaticoside (0-20 µM) did not induce cardiomyocyte cytotoxicity. Asiaticoside (20 µM) mitigated OGD/R-induced autophagy, cytotoxicity, oxidative stress, and myocardial injury. Rapamycin, an autophagy inductor, reversed the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury, whereas 3-methyadanine, an autophagy inhibitor, played an opposite effect. Asiaticoside (20 µM) attenuated OGD/R-induced Wnt/ß-catenin signaling inactivation, which was reversed after transfection with si-ß-catenin. Transfection with si-ß-catenin attenuated the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury. In conclusion, asiaticoside protected against OGD/R-induced cardiomyocyte cytotoxicity, oxidative stress, and myocardial injury via blunting autophagy through activating the Wnt/ß-catenin signaling, indicating the therapeutic potential of asiaticoside in myocardial ischemia/reperfusion injury.