首页|基于网络药理学、分子对接与实验验证揭示槲皮素治疗腹泻型肠易激综合征的潜在分子机制

基于网络药理学、分子对接与实验验证揭示槲皮素治疗腹泻型肠易激综合征的潜在分子机制

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目的:探索槲皮素治疗腹泻型肠易激综合征(Diarrhoeal irritable bowel syndrome,IBS-D)的潜在作用机制。方法:从TCMSP、SwissTar-getPrediction、BATMAN-TCM数据库获得槲皮素的潜在靶点,以"diarrhea irritable bowel syndrome"作为关键词检索GeneCards数据库,得到IBS-D的相关靶点,将槲皮素与IBS-D的靶点取交集。通过Cytoscape 3。7。1软件构建PPI网络。交集靶点导入DAVID数据库进行GO功能分析和KEGG途径富集分析。利用分子对接观察槲皮素与核心靶点的结合能力;在此基础上,建立IBS-D大鼠模型,给予槲皮素进行干预,通过HE染色、ELISA检测对网络药理学预测结果进行实验验证。结果:网络药理学分析显示,TP53,TNF-α,AKT1,VEGF-A,IL-6因子和MAPK、PI3K-Akt信号通路作为槲皮素治疗IBS-D的核心靶点和通路;动物实验结果发现,槲皮素能抑制TP53,TNF-α,AKT1,VEGF-A,IL-1β和IL-6的分泌,减轻炎症反应,改善IBS-D。结论:槲皮素可能下调TP53,TNF-α,AKT1,VEGF-A,IL-1β和IL-6的表达保护结肠组织,从而治疗IBS-D。
Based on network pharmacology,molecular docking and experimental validation to reveal the potential molecular mechanism of quercetin for the treatment of diarrheal irritable bowel syndrome
Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network phar-macology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1β and IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1β and IL-6,thereby treating IBS-D.

QuercetinDiarrheal irritable bowel syndromeNetwork pharmacologyMolecular dockingInflammatory re-sponseMechanism of action

冯敏超、罗芳、谢胜、陈祖民、谭瑾轩、李凯、陈国忠、王道刚

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广西中医药大学,广西 南宁 530001

广西中医药大学第一附属医院,广西 南宁 530001

槲皮素 腹泻型肠易激综合征 网络药理学 分子对接 炎症反应 作用机制

国家自然科学基金资助项目广西壮族自治区医疗卫生适宜技术开发与推广应用项目广西中医药大学研究生教育创新计划项广西中医药大学科研面上项目

82160890GZSY23-21YCSW20233832019MS016

2024

海南医学院学报
海南医学院

海南医学院学报

CSTPCD北大核心
影响因子:1.068
ISSN:1007-1237
年,卷(期):2024.30(3)
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