N-methylcytisine Ameliorates Dextran-sulfate-sodium-induced Ulcerative Colitis Via Inhibiting TLR4/MyD88/NF-?B Signal Pathway In Mice

Objectives In this study,we investigated the protective effect of N-methylcytisine(NMC)in a dextran sulfate sodium(DSS)-induced ulcerative colitis model and to explore its possible mechanisms.Methods Experimental colitis was induced by giving 5%DSS for 7 consecutive days.Different doses of NMC(1,4 and 16 mg/kg)were given orally once everyday for 7 days.1.The protective effect of NMC was evaluated using the disease activity index,weight loss,colon length,results of histopathological examination and myeloperoxidase activity.2.The expression levels of tumour necrosis factor-?,interleukin-1? and interleukin-6(IL-6)in colon tissue of mice were assessed using ELISA.3.The expression levels of TLR4 and NF-?B p65 in colon tissue of mice were determined using Immunohistochemistry.4.The protein expression levels of TLR4?MyD88?TRAF6?I?B?p-I?B?NF-?B p65?p-NF-?B p65 and COX-2 were assessed using Western blot.5.The mRNA levels of TLR4 and MyD88 in colon tissue of mice were quantified using qPCR.Results 1.Compared to the DSS-treated group,NMC(4mg/kg?16mg/kg)attenuated the DSS-induced clinical symptoms and pathological damage(P <0.05,P <0.01).2.Compared to the DSS-treated group,NMC(4mg/kg?16mg/kg)significantly reduced myeloperoxidase activity and level of tumour necrosis factor-?,interleukin-1? and interleukin-6(IL-6)in colon tissue of mice(P <0.05,P <0.01).3.Compared to the DSS-treated group,NMC(16mg/kg)significantly inhibited the protein expression levels of TLR4?MyD88?TRAF6?I?B?p-I?B?NF-?B p65?p-NF-?B p65 and COX-2.Meanwhile,NMC can decrease the mRNA levels of TLR4 and MyD88 in colon tissue of mice(P <0.05).Conclusions NMC has significantly protective effect against on DSS-induced colitis in mice,which may be associated with blocking of the TLR4/MyD88/NF-?B signaling pathway.