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

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-alpha, TGF-beta1), platelet-derived growth factor (PDGF), interleukin (IL-1alpha,beta, IL-6) and tumor necrosis factor (TNF-alpha). Sho-saiko-to (TJ-9; Xiao-Chai-Hu-Tan- 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-beta1, PDGF mRNA expression, the amount of IL-1alpha, IL-1beta, IL-6, TNF-alpha and the fibrotic marker "PIII NP" in the serum. Then, using the immunohistochemical stain to observe the TGF-beta1 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-beta1 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-1beta and enhanced the production of TNF-alpha. 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-beta1 and PDGF. These results also confirmed by the immunohistochemical staining of TGF-beta1. (2) TJ-9 at a dose of 0.5 g/(kg day) suppressed the increasing tendency of IL-1beta and Stimulated the production of TNF-alpha to inhibit Ito cell proliferation and collagen formation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.