Herbal medicine Sho-saiko-to (TJ-9) prevent liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient -amino acid-defined diet

Background/Aim: A herbal medicine, Sho-saiko-to (TJ-9), has recently been orally administered to patients with chronic liver disease in Japan and has been reported to inhibit the development of hepatocellular carcinoma. The aim of this study was to investigate whether TJ-9 has an inhibitory effect on the development of preneoplastic lesions and liver fibrosis in rats. Methods: The effects of the TJ-9 were examined using the choline-deficient -amino acid-defined (CDAA) diet-induced liver fibrosis model in 16-week-old male Wistar rats. Results: TJ-9 (1% w/w) prevented fibrosis, as indicated by reduced hydroxyproline content in the liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic acid), without reducing the increase in serum alanine aminotransferase and aspartate aminotransferase. TJ-9 also reduced the expression of type III procollagen alpha 1 mRNA in the liver, as well as the proliferation of myofibroblast-like cells (activated stellate cells, activated Ito cells). Furthermore, TJ-9 reduced and the number of preneoplastic lesions, detected as enzyme-altered (gluthathione S-transferase placental form-positive) lesions, in the liver. Conclusions: These results indicate that the herbal medicine Sho-saiko-to (TJ-9) prevents fibrosis as well as preneoplastic lesions, not by inhibiting hepatocyte cell death but by inhibiting the activation of stellate cells, which are considered to be the main collagen-producing cells, leading to a reduction in the development of preneoplastic lesions.