Abstract
Background: Advanced liver fibrosis can lead to cirrhosis, resulting in an accelerated risk of liver failure and hepatocellular carcinoma. It is necessary to develop an effective antifibrotic strategy. It has been reported that Fuzheng Huayu formula (FZHY) had a remarkable anti-hepatic fibrosis effect. Here, We obtain a new anti-fibrotic composition, which consists of the main active ingredients of FZHY formula and investigate its mechanism of pharmacological action.Methods: The main active ingredients of FZHY through the quantitative analysis in FZHY extracts and FZHY-treated plasma and liver in rats were investigated. The best anti-fibrotic composition of the main active ingredients was studied through the uniform design and validation experiments in vivo and its mechanism was evaluated in CCl4- and BDL-induced liver fibrosis models in rats and mice and TGF-β1-indued LX-2 cells activation model in vitro.Results：A novel composition, namely JY5 formula, which consisted of Salvianolic acid B, schisantherin A and amygdalin, the main active components of FZHY, could significantly alleviated hepatic hydroxyproline content and collagen deposition in CCl4- and BDL-induced fibrotic liver in rats and mice. Further studies showed that JY5 could inhibit the activation of hepatic stellate cells (HSCs) through inactivating Notch signaling in vivo and in vitro.Conclusions: We found a novel composition JY5 formula, which had an anti-hepatic fibrotic effect through inhibiting Notch signaling pathway, consequently suppressing HSCs activation. These results may provide some adequate scientific basis for the clinical research and application of JY5 formula, as a potential new therapeutic candidate for liver fibrosis.
LY2109761, Transforming Growth Factor β Receptor Type I and Type II Dual Inhibitor, is a Novel Approach to Suppress Endothelial Mesenchymal Transformation in Human Corneal Endothelial Cells
