The role of TGF-beta 1 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-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-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/(kgday) 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/(kgday) 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 0.5g/(kgday) 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/(kgday) suppressed the increasing tendency of IL-1beta and stimulated the production of TNF-alpha to inhibit Ito cell proliferation and collagen formation.
Chen
Ming-Ho
MH
Research Institute of Chinese Medicine, Chinese Medical University, Taichung, Taiwan, ROC.
Chen
Jung-Chou
JC
Tsai
Chin-Chuan
CC
Wang
Wen-Chuang
WC
Chang
De-Ching
DC
Tu
Dom-Gene
DG
Hsieh
Hsiao-Yen
HY
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D004365:Drugs, Chinese Herbal; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C461320:shosaiko-to