trans-Polydatin protects the mouse heart against ischemia/reperfusion injury via inhibition of the renin–angiotensin system (RAS) and Rho kinase (ROCK) activity

Background: Recent studies highlighted the protective benefits of a Chinese herb extract from poly- gonum cuspidatum, trans-polydatin, on cardiac disease. We investigated the therapeutic effect of trans- polydatin on myocardial ischemia/reperfusion (IR) injury and the underlying mechanisms related to the renin–angiotensin system (RAS) and RhoA kinase (ROCK) pathway. Methods and results: Experiments were performed on neonatal rats’ ventricular myocytes that were subjected to hypoxia–reoxygenation (simulated IR, SIR) and on adult mice which were subjected to left anterior descending coronary artery occlusion for 45 min followed by a one-week reperfusion. trans-Polydatin significantly increased cell via- bility and reduced apoptosis in SIR cardiomyocytes. It was also observed to reduce the infarct size and increase the cardiac function in IR mice. trans-Polydatin decreased the expression of angiotensin and inhibited the activities of renin and angiotensin-converting enzyme. Furthermore, trans-polydatin inhibited ROCK activity, especially the angiotensin I receptor-activated ROCK pathway. Conclusions: trans-Polydatin exerts a cardio-protection against myocardial IR injury likely through inhibiting both RAS and the downstream ROCK pathway.