Salvianolic Acid C Activates the AMPK Pathway to Inhibit Ferroptosis and Alleviate Cardiomyocyte Injury after Acute Myocardial Infarction

Myocardial infarction (MI) is one of the leading causes of death worldwide and results in substantial harm to human health and family well-being. Salvianolic acid C (SAC), a bioactive compound isolated from Salvia miltiorrhiza Bge., exhibits anti-oxidant, anti-inflammatory, and anti-apoptotic capacities. However, the protective effects of SAC against MI-induced cardiomyocyte injury and the underlying molecular mechanisms, particularly its role in ferroptosis and AMPK signaling, remain unclear. Infarct size in rat hearts was assessed through triphenyltetrazolium chloride (TTC) staining. Myocardial tissue damage was examined through hematoxylin-eosin (HE) staining. The mRNA and protein levels of inflammatory cytokines, including Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis in myocardial tissues was evaluated through the terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) assay. Protein expression levels were determined by Western blot. The results demonstrated that SAC significantly reduced infarct size in MI rats. Inflammation and cardiomyocyte apoptosis were markedly increased in the MI group, but these impacts were neutralized after SAC treatment. In addition, SAC effectively suppressed ferroptosis in MI rats. Mechanistically, SAC activates the AMPK pathway. Finally, SAC was shown to alleviate oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury by activating the AMPK pathway. This study is the first to demonstrate that SAC activates the AMPK pathway to inhibit ferroptosis and alleviate cardiomyocyte injury after acute MI. These findings suggest that SAC may present a promising therapeutic candidate for the treatment of MI.