Inhibitory effects of Japanese herbal medicines sho-saiko-to and juzen-taiho-to on nonalcoholic steatohepatitis in mice

PLoS One. 2014 Jan 22;9(1):e87279. doi: 10.1371/journal.pone.0087279. eCollection 2014.

Abstract

Although Japanese herbal medicines (JHMs) are widely used in Japan, only a few studies have investigated their effects on nonalcoholic steatohepatitis (NASH). In the present study, we examined the effect of 4 kinds of JHMs [sho-saiko-to (TJ-9), inchin-ko-to (TJ-135), juzen-taiho-to (TJ-48), and keishi-bukuryo-gan (TJ-25)] on a mouse model of NASH. Db/db mice were divided into 6 groups: control diet (control), methionine- and choline-deficient diet (MCD), and MCD diet supplemented with TJ-9, TJ-135, TJ-48, and TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. Serum alanine aminotransferase levels and liver histology, including necroinflammation and fibrosis, were significantly alleviated in the TJ-9 and TJ-48 groups compared with the MCD group. The expression level of transforming growth factor (TGF)-β1 mRNA in the liver was significantly suppressed by TJ-48. Although the differences were not statistically significant, the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were lower, and those of peroxisome proliferators-activated receptor (PPAR)γ were higher in the TJ-9 and/or TJ-48 groups than in the MCD group. Similarly, even though the results were not statistically significant, malondialdehyde levels in liver tissues were lower in the TJ-9 and TJ-48 groups than in the MCD group. We showed that JHMs, especially TJ-9 and TJ-48, inhibited the necroinflammation and fibrosis in the liver of a mouse model of NASH, even though the mechanisms were not fully elucidated. Further studies are needed in the future to investigate the possibility of clinical application of these medicines in the treatment for NASH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Analysis of Variance
  • Animals
  • DNA Primers / genetics
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Fatty Liver / drug therapy*
  • Fatty Liver / pathology
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / pathology
  • Medicine, Kampo / methods*
  • Mice
  • Non-alcoholic Fatty Liver Disease
  • PPAR gamma / metabolism
  • Phytotherapy / methods*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / metabolism

Substances

  • DNA Primers
  • Drugs, Chinese Herbal
  • PPAR gamma
  • Transforming Growth Factor beta1
  • inchinko-to
  • juzentaihoto
  • keishibukuryogan
  • shosaiko-to
  • Alanine Transaminase

Grants and funding

This work was supported by Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research Grant Number 23790753 (URL: http://www.jsps.go.jp/j-grantsinaid/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.