title: Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.
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.
authors: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Ken
authors: K
authors: Inoue
authors: Yuji
authors: Y
authors: Naito
authors: Tomohisa
authors: T
authors: Takagi
authors: Natsuko
authors: N
authors: Hayashi
authors: Yasuko
authors: Y
authors: Hirai
authors: Katsura
authors: K
authors: Mizushima
authors: Ryusuke
authors: R
authors: Horie
authors: Kohei
authors: K
authors: Fukumoto
authors: Shinya
authors: S
authors: Yamada
authors: Akihito
authors: A
authors: Harusato
authors: Ikuhiro
authors: I
authors: Hirata
authors: Tatsushi
authors: T
authors: Omatsu
authors: Naohisa
authors: N
authors: Yoshida
authors: Kazuhiko
authors: K
authors: Uchiyama
authors: Takeshi
authors: T
authors: Ishikawa
authors: Osamu
authors: O
authors: Handa
authors: Hideyuki
authors: H
authors: Konishi
authors: Naoki
authors: N
authors: Wakabayashi
authors: Nobuaki
authors: N
authors: Yagi
authors: Hiroshi
authors: H
authors: Ichikawa
authors: Satoshi
authors: S
authors: Kokura
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020835:Medicine, Kampo; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D014456:Ulcer / Q000139:chemically induced / Q000188:drug therapy; D032106:Zanthoxylum; D030521:Zingiberaceae
chemical_list: D024042:Collagen Type I; D005765:Gastrointestinal Agents; D050958:HSP47 Heat-Shock Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C121414:dai-kenchu-to; D014302:Trinitrobenzenesulfonic Acid