Adenine inhibits TNF-α signaling in intestinal epithelial cells and reduces mucosal inflammation in a dextran sodium sulfate-induced colitis mouse model

Toshihiko Fukuda, Kaustav Majumder, Hua Zhang, Patricia V. Turner, Toshiro Matsui, Yoshinori Mine

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4227-4234
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume64
Issue number21
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences

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