Tangshen Formula Improves Diabetes-Associated Myocardial Fibrosis by Inhibiting TGF-beta/Smads and Wnt/beta-Catenin Pathways

Cardiovascular disease has become the main cause of death among complications of diabetes. Myocardial fibrosis is a crucial pathological change of cardiovascular disease. Tangshen Formula (TSF) shows a good clinical effect in the treatment of diabetic kidney disease (DKD). However, whether TSF alleviates diabetes-associated myocardial fibrosis is still unknown. In the present research, we studied the effect and mechanism of TSF in the treatment of myocardial fibrosis in vivo and in vitro. We found that TSF treatment significantly downregulates myocardial fibrosis-related markers, including collagens I and III, and alpha-SMA. TSF also protects primary mouse cardiac fibroblast (CF) from transforming growth factor-beta 1- (TGF-beta 1-) induced damage. Moreover, TSF decreased the expression levels of TGF-beta/Smad-related genes (alpha-SMA, collagens I and III, TGF-beta 1, and pSmad2/3), and increased Smad7 gene expression. Finally, TSF decreased the expressions of wnt1, active-beta-catenin, FN, and MMP7 to regulate the Wnt/beta-catenin pathway. Taken together, TSF seems to attenuate myocardial fibrosis in KKAy mice by inhibiting TGF-beta/Smad2/3 and Wnt/beta-catenin signaling pathways.