4.7 Article

Adenine Inhibits TNF-α Signaling in Intestinal Epithelial Cells and Reduces Mucosal Inflammation in a Dextran Sodium Sulfate-Induced Colitis Mouse Model

Journal

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 64, Issue 21, Pages 4227-4234

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.6b00665

Keywords

adenine; dextran sodium sulfate; intestinal epithelial cell; pro-inflammatory cytokines; colitis; AC/PKA pathway

Funding

  1. Japan Society for the Promotion of Science [14J03039]
  2. Advanced Foods and Materials Network (AFMNet)
  3. Grants-in-Aid for Scientific Research [14J03039] Funding Source: KAKEN

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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-alpha-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.

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