Upregulation of SIRT1 contributes to the cardioprotective effect of Rutin against myocardial ischemia-reperfusion injury in rats

Abstract The mechanisms underlying beneficial actions of Rutin, a food derived-polyphenolic bioflavonoid, against myocardial ischemia-reperfusion (MI/R) injury were detected. We found that Rutin could significantly ameliorate infarct size and attenuate cardiac dysfunctionto in some extent. Additionally, Rutin could also improve variation of myocardial zymogram and up-regulate antioxidant systems in heart. The selective SIRT1 inhibitor, Ex-527, exacerbated MI/R injury as evidenced by further increased oxidative stress and infracted area in heart tissue. Importantly, Ex-527 abolished the cardioprotective effect of Rutin in MI/R rats. Docking analysis further demonstrated the vital role of SIRT1 on Rutin's cardioprotective effect. We found that activation of SIRT1/Nrf2 signaling induced by Rutin contributes to the reduced oxidative stress, along with decreased apoptosis of cardiomyocytes in heart tissue. Overall, our findings suggest that SIRT1/Nrf2 signaling pathway may be a potential therapeutic target for the treatment of oxidative stress and apoptosis related myocardial diseases.