HERBAL MEDICINE SHO-SAIKO-TO (TJ-9) PREVENTS LIVER FIBROSIS AND ENZYME-ALTERED LESIONS IN RAT-LIVER CIRRHOSIS INDUCED BY A CHOLINE-DEFICIENT L-AMINO ACID-DEFINED DIET

Background/Aim: A herbal medicine, Sho-saiko-to (TJ-9), has recently b een orally administered to patients with chronic liver disease in japa n and has been reported fed to inhibit the development of hepatocellul ar carcinoma. The aim of this study was to investigate whether TJ-9 ha s an inhibitory effect on the development of preneoplastic lesions and liver fibrosis in rats. Methods: The effects of the TJ-9 were examine d using the choline-deficient L-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 con tent in the liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic acid), without reducing the increase is serum ala nine aminotransferase and aspartate aminotransferase. TJ-9 also reduce d the expression of type III procollagen alpha 1 nRNA in the liver, as well as the proliferation of myofibroblast-like cells (activated stel late cells, activated Ito cells). Furthermore, TJ-9 reduced the number of preneoplastic lesions, detected as enzyme-altered (glutathione S-t ransferase 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 cel ls, which are considered to be the main collagen-producing cells, lead ing to a reduction in the development of preneoplastic lesions.