Anti‐inflammatory Effect of Betulin in Acetic Acid Induced Ulcerative Colitis: Effect on TLR4/NF‐kB

Abstract

Background Ulcerative colitis (UC) is a common inflammatory bowel disease. The importance of experimental models for investigating the pathogenic mechanisms and assessment of potential therapeutic agents for UC is well established. Betulin is a natural triterpene compound that has been reported to exert wide spectrum of pharmacological and biological activities. Aim of the work The present study aims to evaluate the potential therapeutic effect of betulin against acetic acid (AA)-induced UC in rats. Material and methods Thirty adult Sprague Dawley rats were randomly assigned into three groups: normal control, UC and UC+betulin (8 mg/kg). UC was induced by intracolonic instillation of AA (3% v/v) in 0.9% saline in all study groups except for the normal group. Four days post instillation of AA, UC+betulin group was treated by intraperitoneal administration of betulin once daily for 14 consecutive days. Results Results showed that betulin attenuated AA-induced UC as evident by reduced macroscopic scores, decreased serum C reactive protein (CRP) titer and lactate dehydrogenase (LDH) activity and attenuated histopathological hallmarks including mucosal necrosis, haemorrhage, congestion and inflammatory cells infiltration. Moreover, betulin treatment dampened colonic inflammatory status via downregulation of toll like receptor-4 (TLR4)/Nuclear factor-κB NF-kB axis accompanied by reduction of colonic inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) as well as CD68 immunostaining. Additionally, betulin administration suppressed signs of apoptosis as shown by reduced caspase-3 and caspase-8 immunostaining compared with UC group. Conclusion Our findings demonstrate a novel therapeutic effect of betulin against UC via suppression of TLR4/NF-κB signalling.