Inhibitory effects of Japanese herbal medicines sho-saiko-to and juzen-taiho-to on nonalcoholic steatohepatitis in mice.
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.
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Yoshihisa
Y
Takahashi
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Yurie
Y
Soejima
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Arisa
A
Kumagai
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Masato
M
Watanabe
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Hiroshi
H
Uozaki
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Toshio
T
Fukusato
D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D020835:Medicine, Kampo / Q000379:methods*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D047495:PPAR gamma / Q000378:metabolism; D008517:Phytotherapy / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D047495:PPAR gamma; D053773:Transforming Growth Factor beta1; C078038:inchinko-to; C063587:juzentaihoto; C054593:keishibukuryogan; C461320:shosaiko-to; D000410:Alanine Transaminase