Anti-inflammatory/anti-apoptotic impact of betulin attenuates experimentally induced ulcerative colitis: An insight into TLR4/NF-kB/caspase signalling modulation

Abstract Ulcerative colitis (UC) is an inflammatory bowel disease with limited therapeutic management approaches. The present study evaluated the potential therapeutic impact of betulin on acetic acid (AA)-induced UC in rats. UC was induced by intracolonic instillation of AA (3% v/v). Rats were treated with betulin (8 mg/kg, I.P., once daily) four days post AA instillation and for 14 consecutive days. Betulin attenuated AA-induced UC as evidenced by retracted macroscopic scores, serum CRP titre and LDH activity, attenuated histopathological hallmarks of UC including mucosal necrosis, haemorrhage, congestion and inflammatory cells infiltration. Moreover, betulin dampened UC-associated colonic inflammatory load with modulation of TLR4/NF-kB axis and reduction in colonic inflammatory cytokines; TNF-α, IL1β and IL-6. Nevertheless, betulin suppressed colonic apoptosis with reduced colonic caspase-3 and caspase-8 expression. The current findings confirm a beneficial therapeutic impact of betulin against UC. The prospective underlying mechanisms include down-regulation of TLR4/NF-κB and the subsequent downstream signalling pathways.