BENEFICIAL EFFECTS OF DIETARY RED RASPBERRY AND PURPLE POTATO ON COLITIS IN EXPERIMENTAL MICE MODELS

Shima Bibi

Inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis are chronic relapsing disorders of the gastrointestinal-tract characterized by intestinal-inflammation. Persistent intestinal-inflammation severely impairs intestinal-integrity and activates immune responses increasing the likelihood of colorectal cancer (CRC)-development. Diets rich in polyphenolic and fiber have an inverse association with IBD-development. Red raspberries (RB) and purple potato (PP) are rich sources of bioactive compounds including polyphenols and fiber. The overall aim of this dissertation was to evaluate the effect of dietary RB and PP supplementation on the intestinal barrier function and health in ulcerative colitis, using dextran sulfate sodium (DSS)induced colitis, a common colitis murine model for IBD research. In the first study, six-week-old-male mice were fed a control or RB (5% w/w, n=20/group) diet for 6-weeks. At 4th-week, approximately half of mice in each-group (n=12/group) were subjected to 2.5% DSS-induction for 6-days, followed by 6-days of recovery. RB decreased DSS-induced colitis symptoms, colonic structure distortion, IL-1β, IL-6, IL-17, COX-2, TNF-α, NF-κB signaling, neutrophil infiltration, and xanthene oxidase, while upregulated catalase content in DSS-mice suggesting anti-inflammatory and anti-oxidant activity. RB increased barrier strengthening by reducing claudin-2, and enhancing claudin-3, ZO-1, mucin-2, and activated AMP-activated protein kinase in DSS-mice. In the second study, the role of RB on prevention of CRC-risk during chronic colitis was examined. Mice were fed with control or RB (5% w/w, n=13/group) diet for 10-weeks. At 4th-week, mice were subjected to two-repeated-cycles of 1% DSS (7-days-DSS-treatment, and 14-days -recovery). RB reduced the colitis-symptoms, inflammation, and immune responses, and facilitated epithelium repair associated with suppressed β-catenin and STAT3 signaling. RB enhanced the tumor suppressor p53 stability and reduced oncogenes expression. In summary, RB delayed colitis onset, reduced inflammatory and immune responses, improved intestinal epithelium repair and barrier function, and facilitated anti-cancerous effects. In the third study, mice were fed with a control AIN-93G basal-diet or the diet supplemented with PP (10% w/w, n=20/group) for 7-weeks. At 5th-week, colitis was induced in half of the mice (n=12/group) by 2.5% DSS-induction for 7-days followed by 7-days of recovery. PP improved colitis symptoms, colonic structure distortion, and inflammation in the DSS-mice, suggesting protective effect.

BENEFICIAL EFFECTS OF DIETARY RED RASPBERRY AND PURPLE POTATO ON COLITIS IN EXPERIMENTAL MICE MODELS

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