中国药房2025,Vol.36Issue(21):2662-2667,6.DOI:10.6039/j.issn.1001-0408.2025.21.08
车前草多糖调控TNF-α/NF-κB信号通路和肠道菌群抑制小鼠结肠炎相关结直肠癌的作用研究
Study on the inhibitory effects of polysaccharide from Plantago depressa on colitis-associated colorectal cancer in mice by regulating TNF-α/NF-κB signaling pathway and intestinal flora
摘要
Abstract
OBJECTIVE To study the inhibitory effects of polysaccharide from Plantago depressa(PLP)on colitis-associated colorectal cancer(CAC)in mice and its mechanism.METHODS The mice were randomly divided into control group,model group,PLP low-,medium-and high-dose groups(100,200,400 mg/kg),positive control group(sulfasalazine,455 mg/kg),with 8 mice in each group.Except for control group,the remaining groups utilized azomethane oxide+dextran sulfate sodium to induce CAC model.At the same time,mice in each group were administered the corresponding medicinal solution via gavage once daily for 12 consecutive weeks.After the last medication,disease activity index(DAI),colon length and tumor number were detected;the histopathological morphology of the colon tissue was observed.The levels of inflammatory cytokines[interleukin-1β(IL-1β),IL-6,interferon-γ(IFN-γ),and tumor necrosis factor-α(TNF-α)]in the serum were measured.Additionally,the expression levels of proteins related to the TNF-α/nuclear factor-κB(NF-κB)signaling pathway[NF-κB p65,NF-κB inhibitor protein α(IκBα),NF-κB-inducing kinase(NIK),tumor necrosis factor receptor 1(TNFR1),and tumor necrosis factor receptor-associated factor 2(TRAF2)]in the colon tissue were detected.In addition,the feces of mice were collected to analyze the changes in intestinal flora composition by 16S rRNA high-throughput sequencing.RESULTS Compared with model group,DAI score,tumor number,serum levels of IL-1β,IL-6(except for PLP low-dose group),IFN-γ and TNF-α,as well as phosphorylation levels of IκBα and NF-κB p65 and protein expressions of NIK,TNFR1 and TRAF2(except for PLP low-dose group)in colon tissue,were all decreased significantly(P<0.05);the colon length was significantly increased(P<0.05).The colon tissue exhibited normal glandular structures,with a reduced degree of inflammatory cell infiltration,and no adenocarcinoma formation was observed.The results of gut microbiota analysis revealed that,compared with model group,the relative abundances of Firmicutes,Fusobacteria,and Megamonas in the PLP high-dose group were significantly decreased(P<0.05),while the relative abundances of Bacteradetes and Akkermansia,as well as the Shannon and Chao1 indices,were significantly increased(P<0.05).The relevant pathways through which PLP regulated intestinal flora function primarily included the TNF signaling pathway,Toll-like receptor signaling pathway,and inflammatory bowel disease signaling pathway,among others.CONCLUSIONS PLP can exert inhibitory effects on CAC by inhibiting TNF-α/NF-κB signaling pathway,and regulating intestinal flora.关键词
车前草多糖/结直肠癌/TNF-α/NF-κB信号通路/肠道菌群Key words
polysaccharide from Plantago depressa/colon cancer/TNF-α/NF-κB signaling pathway/intestinal flora分类
药学引用本文复制引用
唐冉,李明..车前草多糖调控TNF-α/NF-κB信号通路和肠道菌群抑制小鼠结肠炎相关结直肠癌的作用研究[J].中国药房,2025,36(21):2662-2667,6.基金项目
安徽省自然科学基金项目(No.2408085MH227) (No.2408085MH227)