Asiatic acid protests against myocardial ischemia/reperfusion injury via modulation of glycometabolism in rat cardiomyocyte.

Asiatic acid is a reported glycogen phosphorylase inhibitor derived from the tropical medicinal plant Centella asiatica and exhibits myocardial protection both in vivo and in vitro. The purpose of this study was to evaluate the effects of asiatic acid on myocardial ischemia/reperfusion (MI/R) injury and investigate the underlying mechanisms associated with the modulation of glycometabolism in cardiomyocyte.

The rats were subjected to MI/R with or without asiatic acid pretreatment. The cardiac function indexes, the size of myocardial infarction, and plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities were detected. Cardiomyocyte apoptosis was analyzed by TUNEL assay. The Akt/GSK-3β activation was measured by Western blot. The glycogen content, plasma glucose and lactate concentrations were determined following MI/R. The mRNA and protein levels of PPARγ and GLUT4 were determined by real-time PCR and Western blot, respectively.Asiatic acid pretreatment significantly improved the cardiac function indexes, attenuated the size of myocardial infarction, reduced LDH and CK activities, and suppressed cardiomyocyte apoptosis after MI/R. Asiatic acid activated Akt/GSK-3β signal pathway in the myocardium following MI/R injury. In addition, asiatic acid effectively suppressed MI/R-induced glycogen breakdown and inhibited the elevation of plasma glucose and lactate concentrations. Asiatic acid treatment increased PPARγ expression at both mRNA and protein levels, and promoted the translocation of GLUT4 to plasma membrane after MI/R insult. However, the effects mediated by asiatic acid on glycometabolism and GLUT4 translocation were reversed by the administration of LY294002, the Akt inhibitor.These findings demonstrated that asiatic acid exerts beneficial effects on MI/R injury in rats. This protection may be related to the modulation of glycometabolism via Akt-dependent GLUT4 translocation and PPARγ activation in ischemic cardiomyocyte.