中国药房2024，Vol.35Issue(17)：2088-2095,8.DOI:10.6039/j.issn.1001-0408.2024.17.06
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
Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response
摘要
Abstract
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.关键词
苦参醇F/溃疡结肠炎/免疫应答/肠道菌群/炎症/氧化应激/16S rDNA测序Key words
kushenol F/ulcerative colitis/immune response/gut microbiota/inflammation/oxidative stress/16S rDNA sequencing分类
药学引用本文复制引用
何旭东,宋成竹,倪皓雨,胡蕴铠,李敏,陈达俊,苏文涛,俞捷,杨兴鑫..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[J].中国药房,2024,35(17):2088-2095,8.基金项目
国家自然科学基金项目(No.82104381,No.82060707) （No.82104381,No.82060707）
云南省南药可持续利用研究重点实验室科技人才和平台计划项目(No.202105AG070012XS2204) （No.202105AG070012XS2204）
云南省教育厅科学研究基金项目(No.2024Y385) （No.2024Y385）
