Jiedu Tongluo decoction attenuates myocardial fibrosis through inhibition of the TGF-β1/Smad2/3 pathway

Abstract Jiedu Tongluo (JDTL) Decoction is a traditional Chinese medicine formula containing three herbal ingredients, and widely used for treating myocardial fibrosis (MF). This study aimed to investigate the molecular mechanism of the effect of JDTL Decoction on myocardial fibrosis.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 results of immunohistochemistry also showed that JDTL treatment can significantly reduce vimentin and α-SMA expression, as well as TGF-β1 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-β1/Smad2/3 pathway through down-regulation of TGF-β1 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 TGFβ1/Smad2/3 signaling pathway.