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

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.

 

Comments：

The study aimed to investigate the antioxidative effects and underlying mechanisms of maslinic acid (MA) on myocardial ischemia-reperfusion injury (MIRI). The researchers induced MIRI in rats by ligating the left anterior descending coronary artery and mimicked oxidative stress in H9c2 cells using hydrogen peroxide (H2O2).

The results showed that MA reduced the MIRI-induced myocardial injury and H2O2-induced cardiomyocyte death in a dose-dependent manner. The researchers also found that MA increased the activities of glutathione and superoxide dismutase while decreasing the levels of reactive oxygen species and malondialdehyde, indicating that MA has potent antioxidative properties.

The researchers further investigated the underlying mechanisms of MA's antioxidative effects and found that it facilitated nuclear translocation of Nrf2, a transcription factor that regulates the expression of antioxidative and detoxifying genes, and activated the Nrf2/HO-1 signaling pathway. At the same time, MA repressed the NF-κB signaling pathway, which is known to play a critical role in inflammation and oxidative stress.

The researchers also observed that MA promoted the intranuclear expression of Nrf2 and HO-1 and reduced the intranuclear expression of NF-κB p65 and TNF-α, suggesting that MA exerts its cardioprotective effect through regulating the crosstalk between the Nrf2 and NF-κB pathways.

In conclusion, the study provides evidence that MA has potent antioxidative properties and exerts its cardioprotective effect through activating the Nrf2/HO-1 pathway and inhibiting NF-κB activation. These findings suggest that MA may have therapeutic potential in the treatment of MIRI and other conditions associated with oxidative stress and inflammation.