Chitosan oligosaccharides ameliorate inflammation in two experimental models of colitis through inhibition of intestinal epithelial cell NF‐kB signaling and apoptosis

Abstract

Dysregulated mucosal immune response and intestinal epithelial barrier defect contribute to pathogenesis of inflammatory bowel disease (IBD). Chitosan oligosaccharide (COS), a biodegradation product of chitosan, has been recently shown to have anti‐inflammatory properties in vitro. We aimed to evaluate the therapeutic potential of COS in the treatment of IBD and to elucidate its mechanism of action. Anti‐inflammatory effects of COS were investigated both in mice and in human colonic epithelial cell line (T84 cells). In dextran sulphate sodium (DSS)‐induced colitis model, COS treatment significantly rescued dead rate and protected against inflammatory intestinal damage with the most effective dose being 10–20 mg/kg/day. In addition, COS treatment suppressed NF‐κB activation and decreased colonic tissue levels of TNF‐α and IL‐6. Similar protective effect was also observed in acetic acid induced colitis models. In T84 cells, COS suppressed NF‐κB activation and production of TNF‐α and IL‐6 under both LPS and TNF‐α‐stimulated conditions. Furthermore, TNF‐α and H2O2‐induced T84 apoptosis was significantly prevented by COS treatment. COS represents a promising therapeutic option in the treatment of IBD, which may preserve the intestinal epithelial barrier integrity and prevent initiation and progression of IBD.This work was supported by the Thailand Research Fund and the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative.