title: The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
abstract: 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.
authors.affiliation: Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Japan. ikeda-1im@h.u-tokyo.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Kayo
authors.initials: K
authors.lastname: Nagashima
authors.forename: Mikio
authors.initials: M
authors.lastname: Yanase
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tomiya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Arai
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tejima
authors.forename: Takako
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kitamura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Isono
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yahagi
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Mie
authors.initials: M
authors.lastname: Inao
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kume
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D009687:Nuclear Proteins; C078038:inchinko-to; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases