Salvianolic Acid B Alleviates Myocardial Ischemia Injury by Suppressing NLRP3 Inflammasome Activation via SIRT1-AMPK-PGC-1α Signaling Pathway.

Salvianolic acid B (SalB) has been extensively investigated in our laboratory for myocardial ischemia (MI) disease. This study mainly aimed to illustrate the relationship between SIRT1 and the therapeutic effect of SalB on MI in rats and hypoxia damage in H9c2 cells. Furthermore, whether the antagonism of NLRP3 by SalB in the injuries mentioned above is related to SIRT1-AMPK-PGC-1α pathway-mediated mitochondrial biogenesis was further investigated. In vivo, 24 h after MI surgery, we found that SalB effectively reduced ST-segment elevation, myocardial infarct size enlargement, cardiac injury markers, myocardial structural abnormalities, and myocardial apoptotic cells in MI injury rats. In vitro, after 4 h of hypoxia exposure, SalB alleviated cell injury, inhibited the production of ROS and IL-1ß, and prevented the loss of mitochondrial membrane potential (MMP). Besides, SalB downregulated the critical components of the NLRP3 inflammasome and upregulated the SIRT1-AMPK-PGC-1α signaling pathway-related molecules in myocardial tissues and H9c2 cells. However, all the above protective effects of SalB on MI could be offset by EX527. Taken together, our findings indicated that SalB could attenuate MI injury by targeting NLRP3, which is at least partially dependent on the SIRT1/AMPK/PGC-1α signaling pathway.

Salvianolic acid B alleviates myocardial ischemic injury by promoting mitophagy and inhibiting activation of the NLRP3 inflammasome.

Ischemic heart disease is a major cause of mortality and disability worldwide. Salvianolic acid B (Sal B) is one of the main water­soluble components of Salvia miltiorrhiza Bge. Numerous studies have demonstrated that Sal B could exert significant anti­inflammatory and cardiovascular protective effects; however, the underlying mechanisms remain unclear. To elucidate the association between myocardial ischemia and inflammation, and to develop effective protective drugs, a rat model of myocardial ischemia was induced using isoproterenol (ISO) and an inflammation model in H9C2 cells was induced with lipopolysaccharide + adenosine triphosphate. Both of these models were treated with different concentrations of Sal B (5, 10 and 15 mg/kg in vivo; 1, 5 and 25 µM in vitro). In vivo, the serum levels of creatine kinase isoenzyme MB, glutamic oxaloacetic transaminase and IL­1ß, the cardiac function and the mRNA expression levels of NLR family pyrin domain­containing 3 (NLRP3) inflammasome components were evaluated using ELISAs, an electrocardiogram, hematoxylin and eosin staining and reverse transcription­quantitative PCR, respectively. The results demonstrated that treatment with Sal B markedly alleviated the acute myocardial ischemic injury induced by hypodermic injection of ISO in rats. In vitro, the results of reactive oxygen species (ROS) detection, JC­1 staining, western blotting and TUNEL assays showed that Sal B treatment significantly inhibited intracellular ROS production, increased the mitochondrial membrane potential, regulated the expression of mitophagy­related proteins, inhibited the activation of the NLRP3 inflammasome and inhibited apoptosis in H9C2 cells. In conclusion, these findings indicated that Sal B exerted protective effects against myocardial ischemic injury by promoting mitophagy and maintaining mitochondrial function.