苦参醇F调节肠道菌群及免疫应答对溃疡性结肠炎小鼠的改善作用机制研究OA北大核心CSTPCD

OBJECTIVE To explore the action mechanism of kushenol F(KSCF)in treating ulcerative colitis(UC)in mice.METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking.C57BL/6J mice were randomly divided by body weight into model group,positive control group(sulfasalazine,703 mg/kg),KSCF group(100 mg/kg),and normal group,with 6 mice per group.The UC model of mice was induced by dextran sulfate sodium solution.During the modeling period,the mice were given relevant medicine intragastrically,once a day,for 7 consecutive days.After the last administration,the disease activity index(DAI)of the mice was scored;the length of the mice's colon was measured;pathological changes in the colon tissue of mice were observed;the levels of lipopolysaccharide(LPS)in serum,myeloperoxidase(MPO),nitric oxide(NO)and superoxide dismutase(SOD)in the colon were detected in mice;the expression levels of occludin and ZO-1 in colon tissue of mice were detected;the proportions of CD3+T,CD4+T,and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+were detected;changes in colonic microbiota were analyzed by 16S rDNA sequencing.RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)and nuclear factor kappa B(NF-κB).Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein.Animal experiment results demonstrated that,compared with the model group,the pathological characteristics of colon tissue in mice were improved in KSCF group.DAI scores,serum levels of LPS,the levels of MPO,NF-κB p65 phosphorylation and NLRP3 protein expression in the colon,and the proportion of CD8+T lymphocytes in the spleen were reduced significantly(P＜0.05).Body weight,SOD levels,expression levels of occludin and ZO-1 in the colon,proportions of CD3+T and CD4+T lymphocytes,and the CD4+/CD8+ratio in the spleen were significantly increased(P＜0.05);the abundance of Firmicutes,Actinobacteria,Akkermansia,and Lactobacillus genera were increased,while Proteobacteria decreased;the microbial community structure tended towards that of the normal group.CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance,enhancing immune response,and inhibiting colonic inflammatory responses,thereby improving intestinal barrier integrity.