The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells

Hitoshi Ikeda, Kayo Nagashima, Mikio Yanase, Tomoaki Tomiya, Masahiro Arai, Yukiko Inoue, Kazuaki Tejima, Takako Nishikawa, Naoko Watanabe, Kazuya Kitamura, Tomomi Isono, Naohisa Yahagi, Eisei Noiri, Mie Inao, Satoshi Mochida, Yukio Kume, Yutaka Yatomi, Kazuhiko Nakahara, Masao Omata, Kenji Fujiwara

研究成果: Article査読

15 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2226-2233
ページ数8
ジャーナルLife Sciences
78
19
DOI
出版ステータスPublished - 2006 4月 4
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)
  • 薬理学、毒性学および薬学(全般)

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