Nobiletin alleviates the hypoxia/reoxygenation-induced damage in myocardial cells by modulating the miR-433/SIRT1 axis

J Food Biochem. 2021 Jun 26:e13844. doi: 10.1111/jfbc.13844. Online ahead of print.

Abstract

The effect of nobiletin (NOB) on myocardial ischemia-reperfusion injury and the underlying mechanism were investigated in this study. Myocardial cells (H9c2) were cultured under hypoxia/reoxygenation (H/R) condition, followed by the treatment with NOB. Next, miR-433 overexpression or silencing was performed in H9c2 cells to further assess the efficacy of NOB. Cell viability and apoptosis were determined using MTT assays and flow cytometry, respectively. Our results demonstrated that NOB treatment led to the upregulation of SIRT1 and inhibited miR-433 expression in H9c2 cells. In addition, we found that miR-433 targeted and inhibited the expression of SIRT1. NOB treatment promoted cell viability and alleviated apoptosis in H9c2 cells. Thus, our findings indicate that NOB may relieve H/R-induced damage in H9c2 cells by modulating the miR-433/SIRT1 axis. PRACTICAL APPLICATIONS: MiR-433 targeted and inhibited the expression of SIRT1. NOB treatment promoted cell viability and alleviated apoptosis in H9c2 cells. Thus, our findings indicate that NOB could effectively relieve H/R-induced damage in H9c2 cells by modulating the miR-433/SIRT1 axis, suggesting that nobiletin may be a potential drug for the treatment of myocardial ischemia-reperfusion injury. Furthermore, this study also identified another potential therapeutic target, miR-433, for the treatment of myocardial ischemia-reperfusion injury.

Keywords: H9c2 cells; SIRT1; miR-433; myocardial ischemia reperfusion injury; nobiletin.