Schisandrol B alleviated diabetic cardiac injury by inhibiting ferroptosis and improving lipid metabolism in mice.

BACKGROUND

Diabetic cardiomyopathy (DCM) is a major complication of diabetes mellitus, highlighting the need to elucidate its pathogenesis and explore potential therapeutic interventions.

PURPOSE: This study aimed to investigate the cardioprotective mechanisms of SolB in DCM using metabolomic and transcriptomic approaches.

METHODS

A DCM mouse model was induced by a high-fat diet combined with streptozotocin (STZ) administration. Cardiac function was assessed, and myocardial structure was examined via echocardiography and HE staining after 10 weeks of SolB treatment. Serum metabolomics and cardiac transcriptomics were performed to identify differentially expressed metabolites and genes, respectively, followed by correlation analysis. Ferroptosis-related proteins were detected by Western blotting (WB). In vitro, H9c2 cells exposed to palmitic acid and high glucose were used to evaluate the effects of SolB on cell viability, ATP production, oxygen consumption, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Ferroptosis inducer and inhibitor were employed to further explore the underlying mechanisms.

RESULTS

SolB did not significantly alter blood glucose levels but markedly improved cardiac function and myocardial structure. Metabolomic analysis revealed that SolB modulated serum metabolic pathways, including carnitine synthesis and fatty acid oxidation et al. Transcriptomic data indicated that SolB influenced ferroptosis-related pathways. Integrated analysis demonstrated that SolB regulated fatty acid degradation, glutathione metabolism, and cysteine and methionine catabolism. In H9c2 cells, SolB enhanced cell viability, suppressed ferroptosis, reduced lactate dehydrogenase (LDH) release, and improved mitochondrial function.

CONCLUSIONS

SolB ameliorates diabetic myocardial injury by inhibiting ferroptosis and improving myocardial lipid metabolism.