Dihydromyricetin Protects Against Hypoxia/Reoxygenation Injury in Cardiomyocytes by Activating miR-34a-Mediated Notch1 Pathway

Dihydromyricetin (Dih), a naturally occurring flavonoid, has been identified to exert a protective effect against ischemia/reperfusion injury. However, the detailed mechanisms remain unclear. Here we investigated the biological role of Dih in preventing hypoxia/reoxygenation (H/R) injury in cardiomyocytes. The results showed that Dih protected cardiomyocytes against H/R-induced Apoptosis, as proved by improved cell viability and decreased Lactate Dehydrogenase (LDH) release, cell Apoptosis percentage, and Caspase-3/7 activity. H/R-induced oxidative stress in cardiomyocytes was also prevented by Dih with increased activities of superoxide dismutase (SOD), Glutathione Peroxidase (GSH-Px), and catalase (CAT), and decreased levels of malondialdehyde (MDA) and Reactive Oxygen Species (ROS). Treatment with Dih prevented H/R-induced increase in the activities of myocardial Enzymes aspartate aminotransferase (AST), creatine kinase-MB (CK-MB), and Creatine Kinase (CK). miR-34a expression was upregulated after H/R stimulation, which could be attenuated by Dih pretreatment. Besides, miR-34a overexpression attenuated the protective effects of Dih against H/R-caused increase in Apoptosis, oxidative stress, and myocardial enzyme activities. Next, we demonstrated that Notch1 was a target molecule of miR-34a. Notch1 overexpression reversed the role of miR-34a in regulating the cardioprotective effect of Dih on H/R injury. These observations indicated that the cardioprotective effect of Dih against H/R injury was mediated by the miR-34a/Notch1 signaling. Dih may be a candidate agent for improving the clinical efficacy of cardiac ischemia/reperfusion injury treatment.

Cardioprotective effect; Dihydromyricetin; Ischemia/reperfusion injury; Notch1; miR-34a.