Daikenchuto, a Kampo Medicine, Regulates Intestinal Fibrosis Associated with Decreasing Expression of Heat Shock Protein 47 and Collagen Content in a Rat Colitis Model

Ken Inoue; Yuji Naito; Tomohisa Takagi; Natsuko Hayashi; Yasuko Hirai; Katsura Mizushima; Ryusuke Horie; Kohei Fukumoto; Shinya Yamada; Akihito Harusato; Ikuhiro Hirata; Tatsushi Omatsu; Naohisa Yoshida; Kazuhiko Uchiyama; Takeshi Ishikawa; Osamu Handa; Hideyuki Konishi; Naoki Wakabayashi; Nobuaki Yagi; Hiroshi Ichikawa; Satoshi Kokura; Toshikazu Yoshikawa

doi:10.1248/bpb.34.1659

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Daikenchuto, a Kampo Medicine, Regulates Intestinal Fibrosis Associated with Decreasing Expression of Heat Shock Protein 47 and Collagen Content in a Rat Colitis Model

Ken Inoue, Yuji Naito, Tomohisa Takagi, Natsuko Hayashi, Yasuko Hirai, Katsura Mizushima, Ryusuke Horie, Kohei Fukumoto, Shinya Yamada, Akihito Harusato, Ikuhiro Hirata, Tatsushi Omatsu, Naohisa Yoshida, Kazuhiko Uchiyama, Takeshi Ishikawa, Osamu Handa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Hiroshi Ichikawa, Satoshi Kokura, Toshikazu Yoshikawa

Author information

Ken Inoue
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Yuji Naito
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Tomohisa Takagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Natsuko Hayashi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Yasuko Hirai
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Katsura Mizushima
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Ryusuke Horie
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kohei Fukumoto
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Shinya Yamada
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Akihito Harusato
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Ikuhiro Hirata
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Tatsushi Omatsu
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Naohisa Yoshida
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kazuhiko Uchiyama
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Takeshi Ishikawa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Osamu Handa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Hideyuki Konishi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Naoki Wakabayashi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Nobuaki Yagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Hiroshi Ichikawa
Department of Medical Life Systems, Doshisya University
Satoshi Kokura
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Toshikazu Yoshikawa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

Keywords: Daikenchuto, heat shock protein 47, myofibroblast

JOURNAL FREE ACCESS

2011 Volume 34 Issue 11 Pages 1659-1665

DOI https://doi.org/10.1248/bpb.34.1659

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Abstract

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time–course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

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