Ursolic Acid Exhibits Protective Property against DSS-induced Ulcerative Colitis in Mice through STAT3 Signaling Pathway

Abstract

Objective:Anti-inflammatory effects of ursolic acid(UA)on a dextran sulfate sodium(DSS)-induced experimental murine colitis models was investigated to elucidate its possible molecular mechanisms on intestinal epithelial cells(IEC).Methods:For in vivo study,a total of 15 male BALB/c mice weighing(20-22)g were randomly divided into three groups:normal control group,DSS model group and DSS+UA treatment group;the mouse colitis model was induced by 3%dextran sodium sulfate(DSS)for 8 days;one of the DSS-induced groups was pretreated with UA.The body weight and colon length of mice in each group were measured by physical balance and vernier caliper,respectively.The mice in each group were scored according to the clinical disease activity index(DAI)score method.HE staining was used to observe the histopathological changes of colon in each group.The changes of serum amyloid protease A(SAA)and IL-6 expression in colon tissue were measured by ELISA.Using IL-6-stimulated differentiated Caco-2 cells as an in vitro inflammatory model of human intestinal epithelium,the effects of UA on the activation of IL-6/signal transducer and activator of transcription 3(STAT3)signal pathway in IEC were examined by Western blot for STAT3 phosphorylation.Results:1)Compared with the normal control group,the DAI score was increased,the length of the colon was shortened,and the histological damage was obvious in the DSS model group(P<0.05);administration of UA significantly reduced the severity of DSS-induced murine colitis as assessed by DAI score,colon length,and histology damage of colon(P<0.05).2)Compared with the normal control group,the SAA level and the IL-6 level of colon tissue in the DSS model group increased significantly.The DSS-induced increases of SAA and colonic IL-6 levels were reversed by UA treatment(P<0.05).3)Compared with normal IEC,IL-6 stimulation significantly increased the phosphorylation level of STAT3;STAT3 phosphorylation in IEC-treated with IL-6 and UA was significantly inhibited compared with only IL-6 stimulation(P<0.05).Conclusion:Our findings implicate that UA ameliorates DSS-induced colonic inflammation by blocking IL-6/STAT3 signaling pathway,and therefore indicate that UA may have clinical potential as a novel targeted therapy for ulcerative colitis.