Paeonol Improves Cardiac Remodelling in MI Mice by Suppressing NOX2 mRNA Expression to Mitigate Oxidative Stress and Mitochondrial Dysfunction.

Myocardial infarction (MI), a primary contributor to mortality from cardiovascular diseases, continues to pose a significant challenge in clinical treatment. In this study, our objective was to investigate the cardioprotective effects of paeonol (PAE) on mice with MI, and to delve into the precise mechanisms underlying these effects. We developed the MI model by ligating the left anterior descending artery in mice and replicated this model in vitro by stimulating H9C2 cells with levarterenol (LN). Cardiac function, infarct size, cardiomyocyte size, apoptosis, and mitochondrial structure were evaluated through echocardiography, Masson's trichrome staining, WGA staining, TUNEL assay, and electron microscopy, respectively. Colorimetry, Western blotting, flow cytometry, RT-PCR, and the dual-luciferase reporter assay were employed to explore the underlying mechanisms. Compared with the model group, PAE significantly ameliorated cardiac dysfunction and hypertrophy, diminished infarct size, cardiomyocyte hypertrophy, and apoptosis, mitigated mitochondrial structural damage, lowered levels of malondialdehyde and NOX2, reduced ROS production, and NOX activity, while enhancing the activities of T-SOD, GSH-PX, and mitochondrial complexes I-V in mice with MI or H9C2 cells subjected to LN intervention. Ultimately, PAE was found to negatively regulate the transcription of NOX2 mRNA in H9C2 cells, partly through inhibition of phospho-STAT3-Y705 protein expression. These results imply that PAE's transcriptional inhibition of NOX2 mRNA expression primarily confers a cardioprotective effect, mitigating myocardial remodelling following MI by improving oxidative stress and mitochondrial dysfunction. This indicates that PAE holds therapeutic promise for the treatment of patients post-MI.