Diosgenin mitigates oxazolone-induced ulcerative colitis in mice via Th2 pathway and pSTAT3 suppression

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by debilitating symptoms and a significant impact on quality of life. Current treatments, including corticosteroids and immunomodulators, often have substantial side effects and may not achieve sustained remission for all patients. There is a pressing need for novel, safer therapeutic agents, particularly those derived from natural sources, that can effectively target the underlying inflammatory mechanisms. This study explores Diosgenin's potential to modulate Th2 pathways and pSTAT3 signaling, key drivers of UC pathogenesis, offering a promising alternative approach.

Male BALB/c mice (10-11 weeks old) were randomized into five groups for a 9-day protocol involving skin sensitization and intra-rectal Oxazolone challenge to induce acute ulcerative colitis. Mice received oral Diosgenin at 3 mg/kg or 30 mg/kg twice daily. A reference control group received Tofacitinib at 60 mg/kg. Disease severity was assessed using clinical activity scores, including Disease Activity Index (DAI), weight loss, diarrhoea, and rectal bleeding. Molecular analyses, including cytokine quantification and pSTAT3 expression, were performed to evaluate mechanistic effects.

Oxazolone successfully induced acute colitis, evidenced by significant weight loss, increased diarrhoea, and an >8-fold increase in rectal bleeding scores compared to vehicle-treated mice (p < 0.05). > Diosgenin-treated mice showed significant recovery, with Disease Activity Index (DAI) scores improving by 40% in the 3 mg/kg group and 45% in the 30 mg/kg group by Day 2, comparable to the 67% improvement seen with Tofacitinib. Stool consistency also improved substantially, with the 30 mg/kg Diosgenin group showing 61% improvement by Day 2, similar to 64% with Tofacitinib. Molecular analysis revealed a dose-dependent suppression of Th2 cytokines: IL-4 levels were reduced by 71% (3 mg/kg) and 90% (30 mg/kg), while IL-13 levels decreased by 75% (3 mg/kg) and 79% (30 mg/kg). Crucially, Diosgenin markedly suppressed colonic pSTAT3 expression, achieving reductions of 92% (3 mg/kg) and 99% (30 mg/kg), mirroring the >90% reduction observed with Tofacitinib.