Prunetin ameliorates myocardial pyroptosis after myocardial infarction by inhibiting the TNF-α/p38 MAPK/ERK pathway.

Background: The inflammatory response in cardiac tissue after myocardial infarction (MI) plays a critical role in myocardial injury. Prunetin (PRU), a natural flavonoid compound, has notable anti-inflammatory properties; however, its role in post-MI myocardial injury and the underlying molecular mechanisms remain unclear. Methods: Network pharmacology was used to predict potential targets of PRU in MI, identifying TNF-α as a high-affinity target. This interaction was further validated by molecular dynamics (MD) simulation and surface plasmon resonance (SPR) assays. A mouse MI model was established to evaluate the protective effects of PRU using echocardiography, histological staining, and serological assays. RNA sequencing was performed to explore the underlying mechanisms, and Western blotting and immunofluorescence were used to assess the TNF-α/p38 MAPK/ERK signaling pathway and pyroptosis-related proteins. R848, a TLR7/8 agonist, was used to induce TNF-α expression and evaluate whether TNF-α activation could reverse the protective effects of PRU. Results: Conclusions: PRU attenuates post-MI myocardial injury by inhibiting TNF-α/p38 MAPK/ERK signaling, thereby reducing cardiomyocyte pyroptosis and inflammatory responses. These findings provide a theoretical basis for the potential development of PRU as a therapeutic candidate for post-MI myocardial injury.