Metformin maintains mucosal integrity in experimental model of colitis by inhibiting oxidative stress and pro-inflammatory signaling.

Metformin, an antidiabetic drug, is well known for its multifarious properties and its ability to modulate inflammatory cascade. Ulcerative colitis (UC) is an inflammatory condition of the colon where drugs exhibiting anti-inflammatory property have been shown to induce and maintain remission. The objective of the present study was to evaluate the efficacy of metformin against acetic-acid induced colitis in rat. The study included five groups of rats namely normal control, experimental control, drug treated groups (50 and 500mg/kg of metformin, MET50, MET500 and 300mg/kg of mesalazine, MSZ300). Parameters like small intestinal transit and colonic macroscopic changes, ulcer score, weight/length (W/L) ratio, levels of oxidative stress and inflammatory markers, tissue histology and expression of COX-2, iNOS, NFκB(p65) were evaluated. The results of this study show that treatment with metformin significantly decreased colonic mucosal damage, maintained oxidative homeostasis and normalized intestinal transit and W/L ratio in a dose-dependent manner. The restorative effect of metformin on colonic mucosa was accompanied by a marked reduction in the tissue levels of pro-inflammatory mediators and immunoreactivity of COX-2, iNOS and NFκB(p65). Further, its protective effect was found to be comparable to that of mesalazine. This study shows that metformin targets oxidative stress and down regulates transcription factor NFκB(p65) mediated pro-inflammatory signaling and has a therapeutic potential in treating inflammatory conditions of the colon.