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/β‐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/β‐catenin signaling inactivation, which was reversed after transfection with si‐β‐catenin. Transfection with si‐β‐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/β‐catenin signaling, indicating the therapeutic potential of asiaticoside in myocardial ischemia/reperfusion injury.

Elucidation of the Biosynthesis of Asiaticoside and Its Reconstitution in Yeast

“…Centella asiatica is a perennial herb with creeping stems belonging to the Umbelliferae family that grows widely in moist and sunny environments. , Asiaticoside, the main functional component of C. asiatica, is a ursane-type triterpenoid saponin that promotes wound healing and neuroprotection and has anti-inflammatory, antiviral, antidiabetic, and cardiomyocyte protection activities. − Asiaticoside is formed by the glycosylation of asiatic acid. A UDP-glucosyltransferase first attaches glucose to the C-28 carboxyl group, which undergoes further glycosylation and successive rhamnosylation reactions to form asiaticoside .…”