Exploring the Potential of IL-1β Inhibitor Diacerein and its Combination with 5-aminosalicylic Acid for the Possible Ameliorating Effect in TNBSinduced Experimental Colitis in Wistar Rats

Abstract

Background: Pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin (IL), and oxidative stress are crucial players in the pathophysiology of inflammatory bowel disease (IBD) that contribute to perpetuating intestinal inflammation. Targeting them presents a novel approach to disease management. In the present study, the potential of an antiosteoarthritic ILinhibitor drug, diacerein (DIA), was investigated in 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)- instigated ulcerative colitis (UC) in Wistar rats. A comparative study was also undertaken to investigate the potential of combination therapy of DIA with the standard drug 5-aminosalicylic acid (5-ASA) versus monotherapy. Methods: Colitis was developed by single intra-colonic administration of TNBS (100mg/kg); whereas drugs 5-ASA (25.5 mg/kg), DIA (100 mg/kg), and DIA+5-ASA (100 + 25.5 mg/kg) were administered orally for five days post-induction to various groups of rats. Parameters like disease activity score, colon/ body weight ratio, colon length, diameter, and gut pH were assessed, and histopathological analysis was carried out. Biochemical markers of colonic inflammation such as IL-1β, TNF-α, reduced glutathione (GSH), and malondialdehyde (MDA) were also estimated. Results: Combination of DIA and 5-ASA demonstrated the most significant reduction of the colon to body weight ratio and disease activity score. It prominently restored the colon length, diameter, and gut pH to normal. It attenuated the biochemical alterations induced by TNBS, indicating a highly significant defensive outcome against colonic inflammation. The histopathological report demonstrated the renovating effect of the combination of disrupted colonic histology with minimally distressing liver, stomach, or pancreas compared to individual drugs. Conclusion: The combination remarkably downregulated the level of inflammation by suppressing both provocative cytokines and reactive oxygen species production. It can be evaluated further used in a clinical setup as a novel and promising drug therapy for UC.