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

ABSTRACT

BACKGROUND: Recent studies highlighted the protective benefits of a Chinese herb extract from polygonum 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 viability 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.