The role of TGF-β1 and cytokines in the modulation of liver fibrosis by Sho-saiko-to in rat's bile duct ligated model

Abstract Liver fibrosis is an over-accumulation of extra-cellular matrix (ECM) and the hepatic stellate cell (Ito cell) play a central role in the pathogenesis of liver fibrosis. There are a lot of growth factors and cytokines involved in the activation of hepatic stellate cell, including of transforming growth factor (TGF-α, TGF-β1), platelet-derived growth factor (PDGF), interleukin (IL-1α,β, IL-6) and tumor necrosis factor (TNF-α). Sho-saiko-to (TJ-9; Xiao-Chai-Hu-Tang in Chinese) was the most popular herbal medicine for the treatment of chronic liver disease in Chinese and Japanese. Our aim of the current study was to examine whether TJ-9 regulated the growth factors and cytokines in the fibrogenesis of bile duct ligated model. Therefore, we assessed the TJ-9's potential in regulating TGF-β1, PDGF mRNA expression, the amount of IL-1α, IL-1β, IL-6, TNF-α and the fibrotic marker “PIII NP” in the serum. Then, using the immunohistochemical stain to observe the TGF-β1 expression in the tissue. Our results showed that TJ-9 at a dose of 0.5 g/(kg day) significantly reduced the serum level of PIII NP, the mRNA expression of TGF-β1 and PDGF. For the cytokines involved in the activation of Ito cell, TJ-9 at a dose of 0.5 g/(kg day) significantly suppressed the increasing tendency of IL-1β and enhanced the production of TNF-α. Finally, we concluded that: (1) TJ-9 at a dose of 0.5 g/(kg day) significantly reduced the serum fibrotic marker PIII NP in the bile duct ligated model, and its mechanism was partly by means of downregulating the mRNA of TGF-β1 and PDGF. These results also confirmed by the immunohistochemical staining of TGF-β1. (2) TJ-9 at a dose of 0.5 g/(kg day) suppressed the increasing tendency of IL-1β and stimulated the production of TNF-α to inhibit Ito cell proliferation and collagen formation.