The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
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DOI：
10.1016/j.lfs.2005.09.024
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发表时间：
2006-04
期刊：
影响因子：
6.1
通讯作者：
H. Ikeda;K. Nagashima;M. Yanase;T. Tomiya;M. Arai;Y. Inoue;Kazuaki Tejima;Takako Nishikawa;N. Watanabe;Kazuya Kitamura;Tomomi Isono;N. Yahagi;E. Noiri;M. Inao;S. Mochida;Yukio Kume;Y. Yatomi;K. Nakahara;M. Omata;K. Fujiwara
中科院分区：
文献类型：
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作者：
H. Ikeda;K. Nagashima;M. Yanase;T. Tomiya;M. Arai;Y. Inoue;Kazuaki Tejima;Takako Nishikawa;N. Watanabe;Kazuya Kitamura;Tomomi Isono;N. Yahagi;E. Noiri;M. Inao;S. Mochida;Yukio Kume;Y. Yatomi;K. Nakahara;M. Omata;K. Fujiwara
使用草药治疗各种疾病在东方医学中有着悠久的传统，肝脏疾病也不例外。在其使用中，缺乏对机制的阐明以及随机、安慰剂对照的临床试验一直是一个问题。最近，我们和其他人报道了inchin-ko-to（TJ-135），一种草药，在动物模型中抑制肝纤维化。在阐明其机制的过程中，我们将研究的重点放在肝星状细胞（hepatic stellate cells，HSCs）上，发现TJ-135诱导的大鼠HSCs形态改变为星形结构，突起细长，呈树枝状，应力纤维较少，这可能是其凋亡的特征。事实上，TJ-135诱导HSC凋亡的时间和浓度依赖性的方式判断的核形态，定量细胞质组蛋白相关的DNA双链体片段和caspase 3活性。在用TJ-135处理的HSC中，确定了p53表达增加和Bcl-2以及磷酸化Akt和Bad表达减少。HSC凋亡被证明参与大鼠肝纤维化自发消退的机制，并且诱导HSC凋亡的试剂已被证明减少大鼠实验性肝纤维化。因此，诱导HSC凋亡可能是TJ-135解决肝纤维化的机制。我们目前的数据可能揭示了草药的新效果。
Use of herbal remedies in the treatment of various diseases has a long tradition in Eastern medicine and the liver diseases are not an exception. In their use, lack of elucidation of mechanism(s) as well as randomized, placebo-controlled clinical trials has been a problem. Recently, we and others reported that inchin-ko-to (TJ-135), one of herbal remedies, suppressed hepatic fibrosis in animal models. In the course of clarifying the mechanism, we directed our focus on hepatic stellate cells (HSCs), playing a pivotal role in hepatic fibrosis, and found that rat HSCs cultured with TJ-135 changed their morphology to star-like configuration with thin, slender and dendritic processes with fewer stress fibers, which might be the features in apoptosis. In fact, TJ-135 induced HSC apoptosis in a time- and concentration-dependent manner as judged by the nuclear morphology, quantitation of cytoplasmic histone-associated DNA oligonucleosome fragments and caspase 3 activity. In HSCs treated with TJ-135, increased expression of p53 and decreased expression of Bcl-2 and phosphorylated Akt and Bad were determined. HSC apoptosis is shown to be involved in the mechanisms of spontaneous resolution of rat hepatic fibrosis and the agent which induces HSC apoptosis has been shown to reduce experimental hepatic fibrosis in rats. Thus, the induction of HSC apoptosis could be the mechanism how TJ-135 works on the resolution of hepatic fibrosis. Our current data may shed light on the novel effect of the herbal remedy.