Effect Of Curcumin On Dextran Sulphate Sodium-induced Ulcerative Colitis In Mice

objective:Ulcerative colitis(UC) which is a form of intestinal inflammatory condition(IBD) is idiopathic,chronic and relapsing inflammatory disorders of the gastrointestinal tract,but its aetiology remains uncertain. Extentive research have revealed cytokines play a central role in modulating inflammation,under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory and anti-inflammatory cytokines. Cytokines could activate nuclear factor-kappaB(NF-κB) through various signaling molecules, Its activation markedly promotes the expression of various pro-inflammatory genes, NF-kappa B strongly influences the course of mucosal inflammation. So the new therapeutic strategies in IBD attempt to block the activation of NF-κB signaling pathway to suppress the release of proinflammatory cytokines and degrade inflammatory reaction . To explore the therapeutic effects and mechanisms of curcumin on dextan sulphate sodium-induced ulcerative colitis in mice, the colitis model was treated with curcumin and the expression of NF-κB and inhibitor of NF-κB(IκB) and the levels of Tumor necrosis factor(TNF)-αand interleukin(IL)-6 were determined in the the colonic inflammatory tissue.Methods : 60 female BALB/c mice were randomly divided into 4 groups ,Group A:the nomal group with administration of animal feeds and water for 7 days,Group B:the experimental colitis group with administration of 5% DSS solution and injection of 25ml/L alcohol solution(with the same volume to group C),Group C:curcumin treatment group with administration of 5%DSS solution and injection of curcumin which was dissolved in 25ml/L alcohol solution(30mg/kg body weight i.p.),Group D:Dexamethasone treatment group with administration of 5%DSS solution and injection of Dexamethasone(0.4mg/kg body weight i.p).All mouse were sacrificed after 7 days,the severity of the colitis was evaluated by the disease activity index(DAI) score,and the colonic mucosal histological changes with H-E staining. TNF-αand IL-6 levels in the colonic tissue were determined by ELISA.The expression of nuclear NF-κB in the intestinal inflammatory cells was determined by immunohistochemistry. The expression of inhibitor of NF-κB(IκB) in intestinal inflammatory cells cytoplasm was determined by Western blotting.Results:1.The DAI scores: The scores of group B was (7.67±1.56) significantly higher than those of the group C(1.64±0.92) and group D(2.80±0.92) (bothP<0.01),and the scores of group C was lower than group D (P<0.01).2.The histologic scores: Biopsy sample that demonstrated the inflammation of colon primarily involved mucosa and submucosa and may extend into serous membrane and demonstrated marked inflammatory cells infiltration of the intestinal mucosa and architectural distortion of the crypts in group B,also the architectural destruction of the crypts and inflammatory cells infiltration in group C and D were lower than group B.The scores of group B was (2.83±0.83)evidently higher than those of group C(1.36±0.50)and group D(2.00±0.67)(both P<0.01),and the scores of group C was lower than group D (P<0.01)。3.The levels of TNF-αand IL-6: The levels of TNF-αlevels and IL-6 in group B were (102.75±3.52)pg/ml,(80.94±3.26)pg/ml respectively, significantly higher than thouse of group C [(75.91±1.59)pg/ml and(59.65±1.39)pg/ml respectively and thouse of group D [(78.25±2.15)pg/ml and(65.57±4.04)pg/ml respectively (all P<0.01), and the levels of IL-6 in group C was less than group D (P<0.01)。4.The NF-κB scores: The immunohistochemistry demonstrated the NF-κB primarily expressed in cytoplasm and cytoblast of group B,and rarely expressed in cytoblast of group C ,also the NF-κB expressed in cytoplasm and cytoblast of group D but the expression was lower than group B. The scores of group B was (7.92±1.24)evidently higher than those of group C (2.73±0.79)and group D(4.22±1.09)(both P<0.01),and the scores of group C was lower than group D(P<0.05)。5.The expression of IκBα: The western blotting demonstrated that the level of IκBαin group B was less than group C and group D(P<0.01).Conclusion:Curcumin has positive effect in treating DSS-induced colitis in mice and the effect is superior to Dexamethasone. Curcumin reduces colonic inflammation through decreasing the expression of NF-κB and modulating the release of cytokines.