Evaluation of Diacerein Efficacy on Colitis as Anti-inflammatory and Anti-oxidant and its Role in Enhancing of Colon Barrier in Mice

Abstract

Ulcerative colitis (UC) is a prevalent disorder characterized by oxidative stress and the release of pro-inflammatory cytokines that disturb the colonic mucosa. Currently, available medicines for UC remain unsatisfactory. Diacerein (DIAC) has exhibited anti-oxidant and anti-inflammatory properties in wide inflammatory disorders. However, the limited understanding of DIAC's role in bowel inflammation has necessitated the investigation of its efficacy in dextran sodium sulfate (DSS)-induced UC in Balb/c mice in this study. Fifty mice were equally divided into five groups. Except for the control, all groups were given DSS for seven days to induce the colitis model. The model was treated with 25 and 50mg/kg/day of DIAC and 00mg/kg/day of 5-aminosalicylic acid (5-ASA) for ten days. Several clinical, molecular and biochemical parameters were evaluated. Following the exposure to DSS, there was a significant upregulation in the pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) and oxidative stress index (MDA). Meanwhile, the concentration of anti-oxidative stress indices (SOD, GPx and CAT) and the levels of IL-10, mucin-1 and 2 and tight junction proteins (TJs) ZO-1 and occludin were markedly suppressed. The colon length and body weight were reduced while DAI and myeloperoxidase (MPO) were elevated. Conversely, DIAC 50mg and 5-ASA significantly reversed the altered pro-inflammatory cytokines, oxidative stress and MPO. Moreover, they significantly restored body weight, colon length, DAI, TJs, mucin-1 and 2 and IL-10. No significant results were found with DIAC 25mg. In conclusion, DIAC exhibited therapeutic effectiveness against colitis. This research may provide hope for testing its effectiveness against UC in humans

Keywords

• oxidative stress
• ulcerative colitis
• tight junctions
• diacerein