Sakaida Isao, Tsuchiya Masako, Kawaguchi Kotarou, Kimura Teruaki, Terai Shuji, Okita Kiwamu
Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505, Japan.
J Hepatol. 2003 Jun;38(6):762-9. doi: 10.1016/s0168-8278(03)00094-1.
BACKGROUND/AIMS: The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis.
The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined.
TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner.
These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.
背景/目的：草药茵陈蒿汤（TJ - 135）由三种草药提取而成，最近有报道称其具有抗凋亡活性。本研究旨在探讨TJ - 135对癌前病变发展以及肝纤维化是否有任何影响。
使用胆碱缺乏的L - 氨基酸限定饮食诱导的肝纤维化模型来检测TJ - 135的作用。此外，还检测了TJ - 135对肝星状细胞系（LI90）中丝裂原活化蛋白（MAP）激酶、III型前胶原mRNA表达以及培养基中N - 末端前胶原III前肽（PIIINP）浓度的影响。
TJ - 135以剂量依赖方式预防纤维化，最高可达1.5%（w/w）。TJ - 135还降低了肝脏中III型前胶原mRNA的表达以及活化星状细胞的数量。此外，TJ - 135减少了肝脏中癌前病变的面积。对于LI90细胞，TJ - 135降低了MAP激酶（ERK和JNK，但不包括P38）的活性，从而以剂量依赖方式降低了培养基中III型前胶原mRNA和PIIINP的浓度。
这些结果表明，尽管TJ - 135具有抗凋亡活性，但它不会增加癌前病变，而是通过抑制星状细胞活化显著降低肝纤维化，且不会减少肝细胞死亡。
