Phloretin Ameliorates Acetic Acid Induced Colitis Through Modulation of Immune and Inflammatory Reactions in Rats

Abstract

Background: Adverse effects associated with current therapy for Ulcerative colitis (UC) over prolonged treatment periods and the high relapse rate limit their use. Incorporating fruits as regular diet has beneficial role in the management of UC. Phloretin, a dihydrochalcone of apple is reported for its anti-oxidant and anti-inflammatory effects. Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats. Methods: In vitro study was performed using Raw 264.7 cells stimulated with LPS (1μg/mL) and in in-vivo study, colitis was induced by intra rectal administration of 4% Acetic acid. Phloretin (50 mg/kg) was given orally for 3 days to Wistar rats after induction for the post-treatment group and 1 day before induction to the pre-treatment group. Macroscopical, biochemical and histopathological evaluations were performed to assess the effectiveness. Results: A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells. Phloretin exerted ameliorative effect in both pre and post-treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase, nitric oxide and eosinophil peroxidase level as well as downregulates colon ICAM-1 gene in acetic acid induced ulcerative colitis in rats. Antioxidative potency was confirmed by restoring tissue GSH level. Phloretin prevents mucosal damage and it was confirmed by histopathological analysis. Conclusion: Collectively, our findings provide evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for future clinical usage.