Matrine ameliorated myocardial ischemia-reperfusion injury through lipid accumulation reduction by activating JAK2-STAT3-CPT1 signaling pathway.

Matrine (MT), the most abundant active compound derived from Sophora flavescens Ait, has demonstrated promising cardioprotective effects against myocardial ischemia-reperfusion (MIR) injury, and is known to reduce excessive triglyceride (TG) level in hyperlipidemia. However, the specific effects and molecular mechanism of MT in regulating cardiac lipid metabolism have remained elusive. This study investigated the role and underlying mechanism of MT in restoring disrupted lipid metabolism in cardiomyocytes. Our results indicate that MT treatment significantly improved MIR-induced cardiac insufficiency and reduced TG accumulation in the heart. Mechanistically, MT significantly promoted CPT1b expression by activating the JAK2-STAT3 phosphorylation pathway, which consequently restored fatty acid oxidation and alleviated lipid droplet deposition. Crucially, the cardioprotective effects of MT, including the reduction of mitochondrial damage and the inhibition of apoptosis, were significantly attenuated when the JAK2 inhibitor was co-administered. In summary, this study suggests a critical role for the JAK2-STAT3-CPT1b signaling pathway in mediating the protective effects of MT against MIR-induced lipid metabolism dysfunction in cardiomyocytes.