The Traditional Chinese Medicine Formula FTZ Protects against Cardiac Fibrosis by Suppressing the TGFβ1-Smad2/3 Pathway

BACKGROUND: Fu fang Zhen Zhu Tiao Zhi (FTZ) is a patented preparation of Chinese herbal medicine that has been used as a natural medicine to treat several chronic diseases including cardiovascular disease. However, its effects on cardiac fibrosis remain unclear. Therefore, this study was designed to investigate the effects and potential mechanisms of FTZ in treating cardiac fibrosis. METHODS: FTZ was administered to mice by oral gavage daily at a dosage of 1.2 g/kg or 2.4 g/kg of body weight for 7 weeks after a transverse aorta constriction (TAC) surgery. Doppler echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were used to assess the effect of FTZ on the cardiac structure and function of mice that had undergone TAC. EdU and wound-healing assays were performed to measure the proliferative and migratory abilities of cardiac fibroblasts. Western blotting and qRT-PCR were used to determine the expression of TGFβ1, Col1A2, Col3, and α-SMA proteins and mRNA levels. RESULTS: FTZ treatment reduced collagen synthesis, attenuated cardiac fibrosis, and improved cardiac function in mice subjected to TAC. Moreover, FTZ treatment prevented the proliferation and migration of cardiac fibroblasts and reduced Ang-II-induced collagen synthesis. Furthermore, FTZ downregulated the expression of TGFβ1, p-smad2, and p-smad3 and inhibited the TGFβ1-Smad2/3 pathway in the setting of cardiac fibrosis. CONCLUSION: FTZ alleviated the proliferation and migration of cardiac fibroblasts and suppressed collagen synthesis via the TGFβ1-Smad2/3 pathway during the progression of cardiac fibrosis. These findings indicated the therapeutic potential of FTZ in treating cardiac fibrosis.