Cannabinoid receptor-2 agonist AM1241 attenuates myocardial ischemia/reperfusion- induced oxidative stress in rats via Nrf2/HO-1 pathway

Cannabinoid type II receptor, also known as CB2 receptor, has been reported to have a protective effect on myocardial infarction. However, CB2 receptor’s role in oxidative stress involved in myocardial ischemia-reperfusion injury (MIRI) and the underlying mechanism has not been fully elucidated. This study aimed to investigate the protective role of cannabinoid receptor-2 agonist AM1241 against MIRI-induced oxidative stress in rats. In addition, the protective effect of AM1241 on oxidative damage of cardiomyocytes injured by hypoxia-reoxygenation (HR) in vitro and its possible mechanism were investigated by establishing a model of HR of H9c2 cardiomyocytes. Clearly, large infarct size and increased number of inflammatory cells were detected in the heart of rats with MIRI. In the meantime, rats in IR group displayed impaired cardiac function as well as promoted myocardial fibrosis and apoptosis rate. Notably, we observed that ROS production was enhanced in the HR-injured cells, while administration of AM1241 caused a reversal effect, leading to improved cell viability, reduced ROS production and elevated expression of Nrf2 and HO-1 in the cardiomyocytes. In Conclusion, AM1241 exerts beneficial effects on relieving MIRI and attenuating oxidative stress possibly by activating Nrf2/HO-1 signaling pathway.