ACEBROPHYLLINE REPROGRAMS INFLAMMATORY AND REDOX SIGNALLING IN EXPERIMENTAL ULCERATIVE COLITIS: A DOSE-DEPENDENT...

Ulcerative colitis (UC) is a chronic inflammatory disease mediated by dysregulated immune responses and oxidative stress, characterised by excessive production of pro-inflammatory cytokines and defective redox homeostasis that leads to mucosal damage. Few therapeutic strategies are therefore able to simultaneously modulate these unified pathways.

This study investigated the prophylactic dose-dependent immunomodulatory and antioxidant effects of acebrophylline in dextran sulfate sodium (DSS)-induced experimental colitis.

Male albino mice were treated with 3% DSS in drinking water for 10 days to induce experimental colitis. Animals were divided randomly into control, DSS, sulfasalazine reference, acebrophylline (5 mg/kg), and acebrophylline (10 mg/kg) groups. Sulfasalazine was included as a reference standard to provide pharmacological context for the effect of acebrophylline. Disease severity was assessed with the clinical disease activity index (DAI), macroscopic parameters, and histopathological analysis. Colonic inflammation levels (TNF-α, IL-1β, IL-6, and IL-10) and oxidative stress markers (MDA, MPO, SOD, and GSH) were determined using ELISA-based assays.

DSS exposure led to severe colitis features such as high DAI scores and increased levels of pro-inflammatory cytokines and oxidative stress parameters, as well as pronounced histopathological damage. In a dose-dependent manner, these changes were significantly reduced by acebrophylline treatment. A higher (10 mg/kg) dose showed more effective inhibition towards TNF-α, IL-1β, and IL-6 and stronger restoration of IL-10. In addition, acebrophylline decreased MDA and MPO levels, indicating the inhibition of lipid peroxidation and neutrophil infiltration, respectively, as well as restored antioxidant defence via an increase in SOD activity and GSH levels. These findings were confirmed by histopathology, revealing enhanced mucosal architecture and less inflammatory infiltration, evident mainly at the high dose.

Acebrophylline has a strong protective effect on DSS-induced colitis with dose-dependent reprogramming of inflammatory and redox signalling. The latter findings indicate that it may fulfil the criteria of a standalone therapeutic candidate by targeting several important pathogenic mechanisms in ulcerative colitis.