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

J Hepatol. 2003 Jun;38(6):762-9. doi: 10.1016/s0168-8278(03)00094-1.

Abstract

Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage*
  • Animals
  • Biomarkers / blood
  • Cell Line
  • Choline / administration & dosage*
  • Collagen Type III / genetics
  • Culture Media / metabolism
  • Diet / adverse effects
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Glutathione Transferase / metabolism
  • Hydroxyproline / metabolism
  • JNK Mitogen-Activated Protein Kinases
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / enzymology*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Oligonucleotide Array Sequence Analysis
  • Peptide Fragments / metabolism
  • Precancerous Conditions / pathology
  • Procollagen / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • Rats
  • Rats, Wistar

Substances

  • Amino Acids
  • Biomarkers
  • Collagen Type III
  • Culture Media
  • Drugs, Chinese Herbal
  • Peptide Fragments
  • Procollagen
  • RNA, Messenger
  • inchinko-to
  • procollagen Type III-N-terminal peptide
  • Glutathione Transferase
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Choline
  • Hydroxyproline