Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis.
OBJECTIVE
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.


RESULTS
Liver fibrosis was induced in rats by repeated injections of carbon tetrachloride (CCl4) or pig-serum. 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.
Inao
Mie
M
Gastroenterology & Hepatology, Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan.
Mochida
Satoshi
S
Matsui
Atsushi
A
Eguchi
Yuichiro
Y
Yulutuz
Yusufu
Y
Wang
Yanhong
Y
Naiki
Kayoko
K
Kakinuma
Tohru
T
Fujimori
Kenji
K
Nagoshi
Sumiko
S
Fujiwara
Kenji
K
D000818:Animals; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D057889:Iridoid Glycosides; D039823:Iridoids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D009336:Necrosis; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D013552:Swine / Q000097:blood
D002756:Cholagogues and Choleretics; D004365:Drugs, Chinese Herbal; D057889:Iridoid Glycosides; D039823:Iridoids; D011714:Pyrans; C078038:inchinko-to; C007835:geniposide; C007834:genipin; D002251:Carbon Tetrachloride