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Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: therapeutic efficacy and possible mechanisms of action

Yousef, M;Pichyangkura, R;Soodvilai, S;Chatsudthipong, V;Muanprasat, C;

Inflammatory bowel disease (IBD) results from intestinal epithelial barrier defect and dysregulated mucosal immune response. This study aimed to evaluate the therapeutic potential of chitosan oligosaccharide (COS), a biodegradation product of dietary fiber chitosan, in the treatment of IBD and to elucidate its possible mechanisms of action. Oral administration of COS protected against mortality and intestinal inflammation in a mouse model of acute colitis induced by 5% dextran sulfate sodium (DSS). The most effective dose range of COS was 10-20 mg/kg/day. In addition, nuclear factor kappa B (NF-B) activation, and levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) in colonic tissues were suppressed in mice receiving COS. Similar protective effect of COS against mortality and intestinal inflammation was observed in another mouse model of acute colitis induced by rectal instillation of 4% acetic acid. Importantly, COS administration after colitis induction was effective in ameliorating intestinal inflammation in both acute colitis models induced by 5% DSS and chronic colitis models induced by cycles of 2.5% DSS. In human colonic epithelial cells (T84 cells), COS treatment prevented NF-B activation, production of TNF- and IL-6, and loss of epithelial barrier integrity under both lipopolysaccharide (LPS) and TNF–stimulated conditions. Furthermore, binding of LPS to T84 cells, and TNF- and oxidative stress-induced apoptosis of T84 cells were prevented by treatment with COS. These results suggest that COS may be effective in the treatment of IBD through inhibition of NF-B signaling and apoptosis of intestinal epithelial cells.

  • PubMed ID: 22475725