title: Adenine Inhibits TNF-α Signaling in Intestinal Epithelial Cells and Reduces Mucosal Inflammation in a Dextran Sodium Sulfate-Induced Colitis Mouse Model.
abstract: Adenine (6-amino-6H-purine), found in molokheiya (Corchorus olitorius L.), has exerted vasorelaxation effects in the thoracic aorta. However, the mode of action of the anti-inflammatory effect of adenine is unclear. Thus, we investigated to clarify the effect of adenine on chronic inflammation of the gastrointestinal tract. In intestinal epithelial cells, adenine significantly inhibited tumor necrosis factor-α-induced interleukin-8 secretion. The inhibition of adenine was abolished under the treatment of inhibitors of adenyl cyclase (AC) and protein kinase A (PKA), indicating the effect of adenine was mediated through the AC/PKA pathway. Adenine (5, 10, and 50 mg/kg BW/day) was administered orally for 14 days to female BALB/c mice, and then 5% dextran sodium sulfate (DSS) was given to induce colitis. Adenine (5 mg/kg BW/day) significantly prevented DSS-induced colon shortening, expression of pro-inflammatory cytokines, and histological damage in the colon. These results suggest that adenine can be a promising nutraceutical for the prevention of intestinal inflammation.
authors.affiliation: Division of Bioresources and Bioenvironmental Sciences, Faculty of Agriculture, Graduate School, Kyushu University , Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kaustav
authors.initials: K
authors.lastname: Majumder
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Turner
authors.affiliation: Division of Bioresources and Bioenvironmental Sciences, Faculty of Agriculture, Graduate School, Kyushu University , Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mine
mesh_terms: D000225:Adenine / Q000008:administration & dosage*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D013431:Sulfates / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D013431:Sulfates; D014409:Tumor Necrosis Factor-alpha; C012036:sodium sulfate; D016264:Dextran Sulfate; D000225:Adenine
keywords: AC/PKA pathway; adenine; colitis; dextran sodium sulfate; intestinal epithelial cell; pro-inflammatory cytokines