基于网络药理学和分子对接技术的含笑内酯缓解痛风性关节炎作用机制研究

Study on mechanism of micheliolide in alleviating gouty arthritis based on network pharmacology and molecular docking technology

为了探讨含笑内酯(MCL)缓解痛风性关节炎(GA)的潜在靶点及相关作用机制.运用网络药理学技术,检索数据库获取MCL和GA相关靶点,筛选两者交集靶点,构建蛋白互作图并筛选核心靶点.进行基因本体(GO)和信号通路(KEGG)富集分析,绘制“MCL-靶点-通路-GA”网络图并对MCL和核心靶点进行分子对接验证.结果共筛选出MCL相关靶点778个,GA相关靶点351个,交集靶点58个.预测TNF和IL-1Β(IL-1β)等24个靶点为MCL缓解GA的核心靶点.GO分析确定生物过程(BP)相关条目294条,细胞组分(CC)相关条目38条,分子功能(MF)相关条目57条.KEGG分析得到105条信号通路,涉及炎症、代谢、感染及肿瘤等多种相关通路.分子对接结果表明MCL可通过氢键与TNF和IL-1Β(IL-1β)等核心靶点紧密结合,其中MCL与IL-1Β(IL-1β)结合最紧密.初步预测了MCL缓解GA的核心靶点及涉及的生物学过程和信号通路,并进行了分子对接验证,为进一步体内外实验提供了思路.

To investigate the potential targets and related mechanisms of micheliolide(MCL)in alleviating gouty arthritis(GA).The network pharmacology technology was used to retrieve MCL and GA related targets,screen their intersection targets,construct protein interaction maps and screen core targets.Enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was conducted,the″MCL-target-pathway-GA″network diagram was drawn,and molecular docking verification of MCL and core target was conducted.Results A total of 778 MCL related targets,351 GA related targets and 58 intersection targets were screened out.Twenty-four targets were predicted to be the core targets of MCL inalleviating GA,such as TNF,IL-1B(IL-1β)and so on.GO analysis confirmed 294 items related to biological process(BP),38 items related to cellular components(CC)and 57 items related to molecular function(MF).KEGG analysis revealed 105 signaling pathways,including inflammation,metabolism,infection and tumor.The molecular docking results showed that MCL binds tightly to the core target of TNF and IL-1B(IL-1β)by hydrogen bonding,and the MCL binds most tightly to the core target of IL-1B(IL-1β).The core targets and related biological processes and signaling pathways of MCL alleviating GA were preliminarily predicted,and molecular docking verification was carried out,providing ideas for further in vivo and in vitro experiments.