Salvianolic acid A attenuated myocardial infarction-induced apoptosis and inflammation by activating Trx.

Myocardial infarction (MI) is a leading cause of mortality worldwide and it is urgent to discover effective therapies. In this study, the protective effect of salvianolic acid A (SAL) on MI induced by left anterior descending coronary artery ligation surgery and H₂O₂-induced H9c2 damage was evaluated. Rats were intraperitoneally injected with SAL once a day for 2 days before MI. At 24-h post-MI, the SAL-treated group showed significantly decreased infarct rate and enhanced myocardial function. Meanwhile, myocardial injury enzymes such as aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) were significantly reduced by SAL treatment. Taking advantage of RNA-seq technology, 52 disease targets of MI were associated with differentially expressed genes after SAL treatment in MI, among which 21 inflammation-related genes and 16 MAPK cascade-related genes were found. Further experiment indicated that SAL treatment reduced inflammatory factors such as IL-1β, IL-6, and TNF-α and decreased tunnel-positive cells and pro-apoptotic Bax after MI. Further investigation revealed that SAL treatment elevated thioredoxin (Trx) and inhibited the activation of c-jun N-terminal kinase (JNK) to attenuate apoptosis and inflammation after MI. Consistently, SAL protected cardiomyocytes against H₂O₂-induced H9c2 damage through increasing cell viability, decreasing cell apoptosis, and activating Trx and inhibiting JNK. Taken together, SAL inhibited cell apoptosis and inflammation through Trx/JNK signaling.