Effects of Ethyl Gallate and Propyl Gallate on Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis in C57BL/6J Mice: Preventive and Protective

Abstract

Objective and design: Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the digestive system marked by oxidative stress, leukocyte infiltration, and elevation of inflammatory mediators. In this study, we demonstrate the protective effect of Ethyl gallate (EG), a phytochemical, and Propyl gallate (PG), an antioxidant, given through normal drinking water (DW) and copper water (CW) in various combinations, which had a positive effect on the amelioration of DSS-induced ulcerative colitis in C57BL/6J mice. Materials and methods: We successfully determined the levels of proinflammatory cytokines and Antioxidant enzymes by ELISA, tracked Oxidative/Nitrosative stress (RO/NS) by in vivo imaging (IVIS) using L-012 chemiluminescent probe, disease activity index (DAI), histopathological and morphometric analysis of colon in DSS-induced Colitis in a model. Results: The results revealed that oral administration of Ethyl gallate and Propyl gallate at a dose of 50 mg/kg considerably reduced the severity of colitis and improved both macroscopic and microscopic clinical symptoms. The limits of proinflammatory cytokines (TNF-α, IL-6, IL-1β and IFN-γ) in colonic tissue were considerably reduced in the DSS+EG-treated and DSS+PG-treated groups, compared to the DSS alone treated group. IVIS imaging of animals from the DSS+EG and DSS+PG treated groups showed a highly significant decrease in RO/NS species relative to the DSS control group, with the exception of the DSS+PG/CW and DSS+EG+PG/CW treated groups. We also observed lower levels of myeloperoxidase (MPO), nitric oxide (NO), and lipid peroxidation (LPO) and higher levels of GST and superoxide dismutase (SOD). In addition, we showed that the EG, PG, and EG+PG-treated groups had a healing impact on DAI score, body weight, and colon length in mice with DSS-induced colitis. In this 21-day study, mice were treated daily with test substances and were challenged to DSS from day 7 to 14. Conclusion: Our study highlights the protective effect of ethyl gallate and propyl gallate in various combinations which, in pre-clinical animals, serves as an anti-inflammatory drug against the severe form of colitis, indicating its potential for the treatment of IBD in humans. In addition, propyl gallate was investigated for the first time in this study for its anti-colitogenic effect with normal drinking water and reduced effect with copper water.