| Inflammatory bowel disease(IBD)is divided into two types:Crohn's disease(CD)and Ulcerative colitis(UC).Among them,UC is the most common,and UC is mainly characterized by severe diarrhea.The blood loss and peristaltic function are gradually lost.NLRP3 inflammatory corpuscles,ERK(1/2 extracellular regulated protein kinases)and p38 were found to be inseparable from the pathogenesis of UC,and have become a hot spot in UC research in recent years.Seabuckthorn polysaccharide(SP)was self-raised by the laboratory.Previous studies have shown that it has preventive and therapeutic effects on CCL4-induced acute liver injury in mice and LPS/D-galN-induced liver inflammation.Thus,we speculate that SP may have a protective effect on inflammatory disease UC.In this experiment,the protective mechanism of seabuckthom polysaccharide was studied by using DSS(Dextran Sulfate Sodium,DSS)to simulate UC model.Forty-eight female C57BL/6 mice were randomly divided into four groups(n=12):Ctrl group(Ctrl),DSS model group(DSS 3.5%),mesalazine-positive drug group(DSS+Mes),seabuckthorn polysaccharide treatment group(DSS+SP).The experimental period was 28 days in total.SP group was orally administered with 200mg/kg/d SP for 28 days,the other groups were given distilled water.On the 22nd day,the Mes group was administered with 60 mg/kg/d Mesalazine for 7 days.At the same time,the mouse free drinking water was replaced with a 3.5%DSS solution.Mice were sacrificed after 7 days of continuous DSS solution drinking.Blood and colon tissue samples were collected for later studies.The results showed that compared with the Ctrl group,the DSS group showed symptoms of weight loss,bloody stools,and thin stools.The disease index(DAI)calculated from these symptoms was significantly increased,and the length of the colon was significantly shortened.It indicates that the ulcerative colitis model was successfully constructed.The length of colon was significantly increased in the SP group compared with the DSS group,and the DAI index was significantly decreased.The HE staining results of colon tissue showed that compared with the DSS group,the intestinal wall edema in the SP group was mild,the intestinal villus epithelium was intact,the neutrophil infiltration was reduced,and the degree of inflammation was alleviated.SP significantly reduced DSS-induced IL-1??IL-6 inflammatory factor expression.Western-blot analysis showed that SP significantly decreased the expression of NLRP3,ASC,Caspase-1?IL-1? induced by DSS.Further studies showed that the phosphorylation levels of ERK1/2 and p38 MAPK(Mitogen Activated Protein Kinase,MAPK)were decreased after SP and Mes administration.SP promotes the expression of ZO-1 protein.In order to further explore the anti-NLRP3 inflammasome effect of seabuckthorn polysaccharide,LPS and ATP were used to activate NLRP3 inflammasome in macrophages,the anti-inflammatory effect and mechanisms of seabuckthorn polysaccharid were studied.The results showed that SP reduced the expression of IL-1? and IL-6.Western blot results showed that SP group inhibited the activation of NLRP3 inflammasome in macrophages.Conclusion:SP alleviate DSS-induced ulcerative colitis by inhibiting the activation of NLRP3 inflammasome and maintaining the integrity of colon barrier.This study laid a foundation for further development and utilization of Seabuckthorn polysaccharides.CONCLUSION:SP exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome components and effector factors as well as p-ERK and p-p-38 MAPK... |
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