Ononin alleviates H2O2-induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway

Ononin (ON) is an isoflavone with numerous reported bioactivities, including anti-oxidative, anti-inflammatory and neuroprotective effects. Autophagy is a critical homeostatic process in the body that has been reported to closely associate with the apoptotic processes of cardiomyocytes. Using flow cytometry, western blotting, echocardiography and Masson's staining, the present study investigated the effects of ON on H₂O₂-induced cardiomyocyte Apoptosis and myocardial infarction, in addition to any potential underlying molecular mechanisms. H₂O₂ treatment reliably induced Apoptosis in H9C2 cells. The anti-apoptotic effects of ON were revealed by flow cytometry results and by the downregulation of cleaved-caspase 3. Further investigations indicated that ON may alleviate Apoptosis by enhancing Autophagy, as evidenced by increased microtubule-associated proteins 1A/1B light chain 3B expression and p62 degradation. Activation of the 5' AMP-activated protein kinase (AMPK)/mTOR pathway was observed after ON administration following H₂O₂-induced cardiomyocyte injury. However, these anti-apoptotic effects mediated by ON were lost after Autophagy inhibition by chloroquine or AMPK inhibition by Compound C. Finally, the protective effects of ON on cardiomyocytes in vitro could also be observed in vivo. A myocardial infarction model was established by ligating the left anterior descending branch of the rat heart. Using echocardiography and Masson's staining, ON was shown to increase the ejection fraction and decrease cardiac fibrosis in rats with myocardial infarction. These results suggest that ON exerts cardioprotective effects by improving Autophagy via the AMPK/mTOR signaling pathway.

5' AMP-activated protein kinase/mTOR; apoptosis; autophagy; cardiac function; cardiomyocyte; ononin.