Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis
Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis
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DOI：
10.1016/j.jhep.2004.06.033
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发表时间：
2004-10-01
影响因子：
25.7
通讯作者：
Fujiwara, K
中科院分区：
文献类型：
--
作者：
Inao, M;Mochida, S;Fujiwara, K
背景/目的：Inchin-ko-to（TJ-135）是日本用于治疗肝硬化黄疸患者的草药。其作为抗纤维化药物的功效与星状细胞活化有关。方法/结果：用四氯化碳（CCl 4）或猪血清诱导大鼠肝纤维化。口服TJ-135可改善CCl 4大鼠的死亡率，降低肝坏死和纤维化程度。在给予猪血清的大鼠中发现了类似的肝纤维化改善，未显示肝坏死。TJ-135以剂量相关的方式降低了从正常大鼠肝脏分离后体外激活的星状细胞的DNA合成，伴随着平滑肌α肌动蛋白表达和收缩性的降低。在用京尼平苷（TJ-135的环烯醚萜化合物）培养的细胞中未发现这种衰减，但是京尼平（通过细菌植物群的作用在肠道中形成的京尼平苷的糖苷配基）显著降低星状细胞活化，而不影响胶原蛋白以外的蛋白质的合成。结论：TJ-135可用于治疗肝纤维化和门静脉高压症，通过京尼平（其组分的吸收形式）抑制活化的肝星状细胞功能。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Inchin-ko-to (TJ-135) is an herbal medicine used in Japan for treatment of icteric patients with cirrhosis. Its efficacy as an anti-fibrogenic drug was evaluated in relation to stellate cell activation. Methods/Results: Liver fibrosis was induced in rats by repeated injections of carbon tetrachloride (CCl4) Or Pigserum. Oral administration of TJ-135 improved the mortality of rats given CCl4 with reduced extents of liver necrosis and fibrosis. Similar improvement of liver fibrosis was found in rats given pig-serum showing no liver necrosis. DNA synthesis of stellate cells activated in vitro after isolation from normal rat liver was decreased by culture with TJ-135 in a dose-related manner, accompanied by decreased smooth muscle alpha actin expression and contractility. Such attenuation was not found in the cells cultured with geniposide, an iridoid compound of TJ-135, but genipin, an aglycone of geniposide formed in the gut by action of bacterial flora, markedly decreased stellate cell activation without affecting synthesis of proteins other than collagen. Conclusions: TJ-135 may be useful for treatment of liver fibrosis and portal hypertension through suppression of activated hepatic stellate cell function by genipin, an absorbed form of its component. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.