Maslinic Acid Ameliorates Myocardial Ischemia Reperfusion Injury-Induced Oxidative Stress via Activating Nrf2 and Inhibiting NF-[Formula: see text]B Pathways

Abstract

Maslinic acid (MA) is a pentacyclic triterpene obtained from the peel of olives that exhibits anti-inflammatory and antioxidant properties in several conditions. Our previous study revealed that MA exerted a cardioprotective effect by repressing inflammation and apoptosis during myocardial ischemia-reperfusion injury (MIRI). However, data regarding the antioxidative effects of MA on MIRI remains limited. This study aims to elucidate the antioxidative roles and underlying mechanisms of MA on MIRI. The left anterior descending coronary artery of rats was subjected to ligate for the induction of the ischemia/reperfusion (I/R) model and the H9c2 cells were exposed to hydrogen peroxide (H₂O₂) to mimic oxidative stress. The results showed that MA reduced the I/R-induced myocardial injury and H₂O₂-induced cardiomyocyte death in a dose-dependent manner. Meanwhile, MA increased the activities of glutathione and superoxide dismutase both in vitro and in vivo while lowering the levels of reactive oxygen species and malondialdehyde. Mechanistically, MA could facilitate Nrf2 nuclear translocation, activate the Nrf2/HO-1 signaling pathway, and repress the NF-[Formula: see text]B signaling pathway both in I/R- and H₂O₂-induced oxidative stress. Besides, MA promoted the intranuclear Nrf2 and HO-1 expression, which could in part be improved by QNZ (NF-[Formula: see text]B inhibitor) in H₂O₂-insulted cells. Conversely, MA markedly reduced the intranuclear NF-[Formula: see text]B p65 and TNF-[Formula: see text] expression, which could be partially abolished by ML385 (Nrf2 inhibitor). Overall, our results indicate that MA, in a dose-dependent manner, mitigated I/R-induced myocardial injury and oxidative stress via activating the Nrf2/HO-1 pathway and inhibiting NF-[Formula: see text]B activation. Furthermore, MA exerts its cardioprotective effect through regulating the crosstalk between the Nrf2 and NF-[Formula: see text]B pathways.

Keywords: Maslinic Acid; Myocardial Ischemia-Reperfusion Injury; NF-[Formula: see text]B; Nrf2; Oxidative Stress.