α-Mangostin protects against myocardial ischemia reperfusion injury by suppressing the activation of HIF-1α

Purpose: To investigate the cytoprotective effect of alpha-mangostin on myocardial tissues in ischemic rats, and the underlying mechanism. Methods: Histopathological changes in myocardial tissues were determined using inverted microscope. Protein expressions were measured by western blotting, while enzyme-linked immunosorbent assay (ELISA) was used to assay the expression levels of caspase-3, caspase-9 and caspase-8. Results: Treatment with alpha-mangostin (20 mg/kg) suppressed production of reactive oxygen species (ROS) and lipid peroxides in myocardial tissues of MI/R rats, and significantly alleviated MI/R injury-mediated reduction in ATP levels in cardiac tissues (p < 0.05). alpha-Mangostin treatment of MI/R injury rats suppressed HIF-1 alpha activation, and markedly elevated BNIP3 levels, relative to model group. Moreover, MI/R-induced cardiomyocyte apoptosis was significantly alleviated by alpha-mangostin treatment (p < 0.05). Treatment with alpha-mangostin also suppressed I/R-induced increases in caspase-8 and caspase-3 activation in myocardial tissues, improved Nrf-2 activation, and promoted HO-1 and GST levels in MI/R injury rats (p < 0.05). Conclusion: These results suggest that alpha-mangostin protects rat cardiac tissues from MI/R-induced oxidative damage via reduction of HIF-1 alpha expression, inhibition of ROS generation and suppression of apoptosis. Therefore, alpha-mangostin may be of therapeutic importance for the management of myocardial ischemia in humans.