Paeonol Can Improve Hypoxic-Induced H9c2 Cells Injury and Ion Channel Activity by Up-Regulating the Expression of CKIP-1

Background: Paeonol is a representative active ingredient of the traditional Chinese medicinal herbs Cortex Moutan, which has a well-established cardioprotective effect on ischemic heart disease. However, there is little evidence of the protective effect of paeonol, and its pharmacological mechanism is also unclear. This study aims to explore the protective effect and mechanism of Paeonol on myocardial infarction rat and hypoxic H9c2 cells. Methods: Myocardial ischemia/reperfusion (I/R) was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion, and then gavage with Paeonol for 7 days. H9c2 cells were applied for the in vitro experiments and hypoxia/reoxygenation (H/R) model was established. CKIP-1 expression was evaluated by qPCR and western blot. The expression of genes involved in apoptosis, inflammation and ion channel was measured by western blot. The currents levels of Nav1.5 and Kir2.1 were measured by whole-cell patch-clamp recording. Results: CKIP-1 expression was decreased in H/R-induced H9c2 cells, which was inversely increased after Paeonol treatment. Paeonol treatment could increase the viability of H/R-induced H9c2 cells and diminish the apoptosis and inflammation of H/R-induced H9c2 cells, while si-CKIP-1 treatment inhibited the phenomena. Moreover, the currents levels of Nav1.5 and Kir2.1 were reduced in H/R-induced H9c2 cells, which were inhibited after Paeonol treatment. Intragastric Paeonol can reduce the ventricular arrhythmias in rats with myocardial infarction. Conclusions: The protective effects of Paeonol on myocardial infarction rats and hypoxic H9c2 cells were achieved by up-regulating CKIP-1.