Jiedu Tongluo Decoction Attenuates Myocardial Fibrosis through Inhibition of the TGF-ß1/Smad2/3 Pathway.

ABSTRACT

Jiedu Tongluo (JDTL) Decoction is a traditional Chinese medicine formula containing three herbal ingredients. It is widely used to treat myocardial fibrosis (MF). This study aimed to investigate the molecular mechanism of JDTL Decoction's effect on MF. In this study, 6 compounds of JDTL Decoction were identified by HPLC. HE and Masson staining showed that in the isoproterenol hydrochloride-induced MF rat model, JDTL treatment can protect the myocardial structure and inhibit the expression of collagen III. The immunohistochemistry results also showed that JDTL treatment can significantly reduce vimentin and α-SMA expression, TGF-ß1 expression, and phosphorylation of Smad2/3 in the rat MF model. RCF, a rat cardiac fibroblast cell line, was used as a tool for in vitro study. Using the methods of hydroxyproline detection, MTT, wound healing test, western blot, and double immunofluorescence staining, our in vitro study confirmed the inhibitory effects of JDTL Decoction on proliferation, migration, and trans-difference ability of RCF cells, as well as the molecular mechanisms underlying the inhibitory effects of JDTL Decoction, including the inhibition of TGF-ß1/Smad2/3 pathway through down-regulation of TGF-ß1 expression and phosphorylation of Smad2/3 as well as the inhibition of the expression of vimentin and α-SMA. In conclusion, JDTL Decoction can prolong the process of myocardial fibrosis through the inhibition of the TGFß1/Smad2/3 signaling pathway.