Title: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
Volume: 17
Issue: 2
Author(s): Supriya Roy, Suneela Dhaneshwar*Tarique Mahmood
Affiliation:
- Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, Sector 125, Noida, 201313, India
Keywords:
Inflammatory bowel disease, ulcerative colitis, anthraquinone derivatives, diacetylrhein, cytokines, oxidative stress.
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.
