Micheliolide reduces the damage, pyroptosis and oxidative stress of cardiomyocytes caused by OGD/R by regulating the AMPK signaling pathway

Myocardial ischemia-reperfusion (I/R) injury remains a devastating clinical problem, contributing substantially to morbidity and mortality worldwide. In the present study, we investigated the potential role of Micheliolide (MCL) in attenuating cardiac I/R injury. H9c2 cardiomyocytes were pretreated with MCL for 24 ‍h and then subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cellular injury was evaluated by measuring cell viability and lactate dehydrogenase (LDH) release, while cell death was assessed using propidium iodide (PI) staining. Oxidative stress was determined by assessing superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity, while the expression levels of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and pyroptosis-related proteins were examined by Western blotting. The results demonstrated that MCL significantly alleviated OGD/R-induced damage in H9c2 cells. Moreover, MCL inhibited OGD/R-induced oxidative stress and pyroptosis while enhancing AMPK pathway activation. Importantly, the protective effect of MCL was attenuated in the presence of the AMPK inhibitor Compound C, indicating that activation of the AMPK signaling pathway is required for MCL-mediated cytoprotection.