The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
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.
Ikeda
Hitoshi
H
Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Japan. ikeda-1im@h.u-tokyo.ac.jp
Nagashima
Kayo
K
Yanase
Mikio
M
Tomiya
Tomoaki
T
Arai
Masahiro
M
Inoue
Yukiko
Y
Tejima
Kazuaki
K
Nishikawa
Takako
T
Watanabe
Naoko
N
Kitamura
Kazuya
K
Isono
Tomomi
T
Yahagi
Naohisa
N
Noiri
Eisei
E
Inao
Mie
M
Mochida
Satoshi
S
Kume
Yukio
Y
Yatomi
Yutaka
Y
Nakahara
Kazuhiko
K
Omata
Masao
M
Fujiwara
Kenji
K
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
D004365:Drugs, Chinese Herbal; D009687:Nuclear Proteins; C078038:inchinko-to; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases