Yu Gan Long Inhibits Liver Fibrosis by Repressing TGF-beta/Smad Signaling and Th17 differentiation

[Speaker] Pengtao You:1
[Co-author] Xia Yu:1, Xiaochuan Ye:1, Yanfang Yang:1, Yanwen Liu:1, Hongwei Li:2
1:Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, China, 2:Wu han Junan Pharmaceutical Co., Ltd, China

Yu Gan Long (YGL) is a traditional empirical formula in China which had been used for liver fibrosis treatment clinically for many years, but its anti-hepatofibrotic mechanisms remains incompletely understood. In this study, we investigated the anti-fibrotic effects of YGL and underlying mechanisms in CCl4-treated rats. The rats were treated with YGL (0.25, 0.5, 1.0 g/kg/d, ig) for 12 weeks, then the serum and liver samples were collected. Serum biochemistry analyses was employed to assess liver function. Serum liver fibrosis markers and inflammatory cytokines were measured by ELISA. Morphological changes of liver tissues were evaluated by HE and Masson staining. The expression of liver fibrogenic proteins and signaling proteins were evaluated by immunohistochemistry. Treatment with YGL significantly attenuated CCl4-induced functional impairment, liver fibrosis and inflammation in a dosage-dependent manner by diminishing levels of AST, ALT and TBIL, decreasing levels of COL4, PC3, HA, LN and alpha smooth muscle actin (alpha-SMA) accumulation, down-regulating expressions of TGF-beta, IL-6, PDGF-BB, IL-1beta and TNF-alpha. Furthermore, the hepatoprotective effects of YGL on fibrosis were associated with downregulation of the phosphorylation of Smad2/3 in the livers of CCl4-treated rats. Moreover, YGL down-regulated the the phosphorylation of Stat3 and expression of IL17A with the downregulation of TGF-beta and IL-6, which involved in the differentiation of Th17. Our results suggested that YGL exerts anti-fibrotic effects in CCl4-treated rats via repressing TGF-beta/Smad signaling and the differentiation of Th17 cells and that blocking this pathway and differentiation may be the central mechanisms by which YGL protects liver from injury.
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