Crocetin alleviates myocardial ischemia/reperfusion injury by regulating inflammation and the unfolded protein response

Crocetin, a natural compound, has been demonstrated to exhibit beneficial effects in cardiovascular diseases. Previous studies demonstrated that crocetin reduced ischemia/reperfusion (I/R) injury by attenuating cytotoxicity and cellular apoptosis. However, the previous mechanistic studies did not fully elucidate its pharmacological effects on cardiac damage, especially I/R injury. The present study verified its cardioprotective effects in a Langendorff perfusion system, an ex vivo model of I/R. It was demonstrated that crocetin significantly attenuated the activities of pro-inflammatory cytokines and nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 signaling. The present study provided novel insight that crocetin regulated the unfolded protein response (UPR) and decreased associated protein levels to protect the heart. Furthermore, it was identified that Nrf2 played a key role in the cardioprotective effect of crocetin by attenuating inflammation and the UPR.