SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY

ABSTRACT Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro . RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.