Salvianolic Acid B Inhibits Myocardial Fibrosis during Diabetic Cardiomyopathy via Suppressing TRPC6 and TGF-β/Smad3 Pathway

Abstract

Salvianolic acid B (Sal B), the main water-soluble polyphenolic constituent of Danshen, is noted for its anti-inflammatory, antioxidant, and antiapoptotic properties, particularly in cardiovascular protection. However, the mechanisms by which Sal B affects myocardial fibrosis require further investigation. In vivo, we established a diabetic mouse model using a high-fat diet and intraperitoneal streptozotocin (STZ) administration. Mice were then treated with Sal B, the transient receptor potential channel 6 (TRPC6) inducers, or their combination. Upregulation of TRPC6 worsened myocardial pathology, leading to cardiac hypertrophy and collagen fiber deposition. In vitro, transforming growth factor (TGF)-β1 induced transdifferentiation of cardiac fibroblasts into myofibroblasts, creating a myofibroblast cell model. Sal B, TRPC6 inducers, or their combination were administered. TRPC6 upregulation increased procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) secretion, promoting myofibroblast proliferation and migration. Our study indicates that TRPC6 expression is upregulated in myocardial fibrosis, enhancing TGF-β/Smad3 signaling and promoting collagen I (COL-1) synthesis. Sal B inhibited abnormal TRPC6 expression and TGF-β/Smad3 activation, mitigating these effects. Thus, Sal B alleviates myocardial fibrosis in diabetes by modulating TRPC6 expression and TGF-β/Smad3 signaling pathway.