Exploring the mechanism of sesamin for the treatment of PM_2.5-induced cardiomyocyte damage based on transcriptomics, network pharmacology and experimental verification

Introduction: Exposure to fine particulate matter (PM_2.5) is known to be associated with cardiovascular diseases. Sesamin (Ses) is a natural phenolic compound found in sesame seeds and sesame oil. Ferroptosis is a novel mode of cell death characterised by iron-dependent lipid peroxidation. This study aims to explore whether PM_2.5 can induce ferroptosis in H9C2 cells and to investigate the precise protective mechanism of Ses.

Methods: Based on transcriptomic data, PM_2.5 may induce ferroptosis in cardiomyocytes. The ferroptosis inducer erastin and ferroptosis inhibitor ferrostatin-1 (Fer-1) were used to illustrate the mechanisms involved in PM_2.5-induced H9C2 cell injury. Using network pharmacology, the pharmacological mechanism and potential therapy targets of Ses were explored for the treatment of PM_2.5-induced cardiomyocyte injury. H9C2 cells were cultured and pretreated with Fer-1 or different concentrations of Ses, and then cardiomyocyte injury model was established using erastin or PM_2.5. Indicators of oxidative responses, including total superoxide dismutase, reduced glutathione, glutathione peroxidase and malondialdehyde, were measured. The expression levels of ferroptosis-related proteins were determined through Western blot analysis.

Results: Results demonstrate that PM_2.5 induces ferroptosis in H9C2 cells and Ses exerts a protective effect by suppressing ACSL4-mediated ferroptosis.

Discussion: Overall, these findings elucidate a novel mechanism by which Ses ameliorates the detrimental effects of PM_2.5 on cardiomyocytes.