Plant‐Derived Polyphenol Salvianolic Acid B Attenuates Cardiomyocyte Pyroptosis by Modulating the MMP12 – NLRP3 Signaling Axis

ABSTRACT Plant‐derived polyphenols are widely investigated as bioactive compounds with potential relevance to cardiometabolic health. Salvianolic acid B (Sal B), a major phenolic compound from Salvia miltiorrhiza , has been reported to exhibit antioxidant and anti‐inflammatory activities; however, its role in cardiomyocyte pyroptosis remains uncertain. In this study, a high glucose (HG)‐stimulated AC16 cardiomyocyte injury model was established to recapitulate the hyperglycemic injury phenotype observed in metabolic cardiomyopathy. Combined functional assays, bioinformatic mining, molecular docking, and matrix metalloproteinase 12 (MMP12) overexpression rescue experiments were performed to explore the protective effects and underlying molecular mechanisms of Sal B activity. The results revealed that Sal B mitigated HG‐triggered oxidative stress and inflammatory response and repressed nucleotide‐binding domain, leucine‐rich–containing family, pyrin domain–containing‐3 (NLRP3)‐dependent cardiomyocyte pyroptosis. MMP12 was identified as a key molecular mediator associated with the protective effects of Sal B, and MMP12 overexpression abrogated the cytoprotective effects of Sal B. These findings provide mechanistic evidence that Sal B modulates MMP12–NLRP3‐associated pyroptotic signaling in cardiomyocyte injury models, supporting further investigation of plant‐derived polyphenols in cardiometabolic nutrition research.