title: Preventive Effect of TU-100 on a Type-2 Model of Colitis in Mice: Possible Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells.
abstract: Purpose. Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), have histopathologically and immunologically different characteristics. We previously reported that a traditional Japanese medicine, daikenchuto (TU-100), ameliorated a trinitrobenzenesulfonic acid- (TNBS-) induced type-1 model colitis exhibiting histopathological features of CD through adrenomedullin (ADM) enhancement. Our current aims were to examine whether TU-100 ameliorates a type-2 model colitis that histologically resembles UC and identify the active ingredients. Methods. TU-100 was administered orally to mice with oxazolone- (OXN-) induced type-2 model colitis. The morbidity was evaluated by body weight loss and the macroscopic score of colonic lesions. ADM was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon ulceration. ADM production by intestinal epithelial cells was increased by TU-100 addition. Screening to identify active ingredients showed that [6]-shogaol and hydroxy α -sanshool enhanced ADM production. Conclusions. TU-100 exerted a protective effect in OXN-induced type-2 model colitis, indicating that TU-100 may be a beneficial agent for treatment of UC.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan ; Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo 065-0033, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Miura
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto