Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.
OBJECTIVE
The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis.


METHODS
The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined.


RESULTS
TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner.


CONCLUSIONS
These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.
Sakaida
Isao
I
Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505, Japan. sakaida@po.cc.yamaguchi-u.ac.jp
Tsuchiya
Masako
M
Kawaguchi
Kotarou
K
Kimura
Teruaki
T
Terai
Shuji
S
Okita
Kiwamu
K
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D002794:Choline / Q000008:administration & dosage*; D024061:Collagen Type III / Q000235:genetics; D003470:Culture Media / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000378:metabolism; D011230:Precancerous Conditions / Q000473:pathology; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D015415:Biomarkers; D024061:Collagen Type III; D003470:Culture Media; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C078038:inchinko-to; C041876:procollagen Type III-N-terminal peptide; D005982:Glutathione Transferase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D002794:Choline; D006909:Hydroxyproline