Protective Role And Mechanism Of Liriodendrin In Mice With DSS-induced Ulcerative Colitis

Aims To investigate the protective effect and mechanism of liriodendrin on dextran sulfate sodium(DSS)-induced ulcerative colitis in mice.Methods(1)In vivo experiments: Experimental colitis was established by giving mice drinking water containing 3%(w/v)DSS for 7 days.Twenty-four BALB/C mice were randomly divided into 3 groups: control group(n = 8);DSS group(n = 8);and liriodendrin plus DSSgroup(n = 8).The mice in theliriodendrin plus DSSgroup received oral administration of liriodendrin(100 mg / kg)3 days before DSS treatment.The control group and the DSS group received an equal volume of water.The mice were sacrificed 7 days after the UC model was induced with DSS.The colon length and disease activity index were assessed.The activity of MPO and antioxidant enzymes were examined in the colon tissue.The proinflammatory cytokines in the colon tissue were detected by Real-time PCR.The level of p-I?B? and p-NF-?B in colon tissues was detected by Western blotting.(2)In vitro experiments: Inflammation of macrophage was established by using LPS.Proinflammatory cytokines in macrophage were detected by Real-time PCR The level of p-I?B? and p-NF-?B in macrophage was detected by Western blotting.Results 1.Liriodendrin improved the clinical symptoms of DSS-induced colitis in mice.The disease activity index of the DSS group was significantly increased compared with the control group,and the disease activity index of the liriodendrin group was significantly reduced compared with the DSS group.In addition,liriodendrin can significantly reverse DSS-induced shortening of the colon length.2.Liriodendrin alleviated colonic pathological lesions of DSS-induced colitis in the colon.Compared with the DSS group,liriodendrin can effectively attenuate DSS-induced pathological lesions.In addition,liriodendrin can significantly inhibit he increase of MPO activity induced by DSS.3.Liriodendrin inhibited proinflammatory cytokines,and increased the activity of antioxidative enzymes in the colon tissue.The level of the m RNA levels of TNF-?,IL-6,and IL-1? in liriodendrin plus DSS group was significantly reduced compared with the DSS group.The activity of SOD and GSH-PX inliriodendrin plus DSS group can be significantly increaded compared with DSS group.In addition,liriodendrin significantly attenuated DSS-induced increases in MDA in the colon tissue.4.Liriodendrin regulated the NF-?B signaling pathway in colon tissue.Compared with the control group,the phosphorylation of I?B? and NF-?B in the colon tissue of the DSS mice was increased,and the treatment of liriodendrin significantly decreased the level of these.5.Liriodendrin inhibited the level of proinflammatory cytokines in LPS induced macrophages RAW264.7.We used lipopolysaccharide(LPS)100 ng / ml)to treat macrophage RAW264.7.We found that different concentrations of liriodendrin significantly inhibited the increasing of TNF-?,IL-6 and IL-1? m RNA induced by LPS-induced macrophage RAW264.7.6.Liriodendrin regulated the NF-?B signaling pathway of macrophage RAW264.7.Pretreatment with Liriodendrin significantly inhibited I?B? and NF-?B phosphorylation compared to LPS alone.Conclusions Liriodendrin significantly ameliorated the severity of DSS-induced mice colitis.The protective effects of liriodendrin involve the increasing of the SOD and GPx activities and a reduction of proinflammatory responses by inhibiting the activation of NF-?B pathways in the colon.In addition,macrophages are involved in this protective effect of liriodendrin.