基于网络药理学的雷公藤治疗干燥综合征作用机制研究

目的:基于网络药理学探讨雷公藤与干燥综合征的关联关系及潜在作用机制。方法:通过检索TCMSP数据库,结合口服生物利用度和类药性分析,筛选出雷公藤中的主要活性成分及作用靶点;检索GEO数据库筛选干燥综合征的预测靶点,并将有效化合物和疾病靶点进行映射;采用Cytoscape软件构建雷公藤化合物-干燥综合征靶点相互作用网络;通过Bisogenet包进行蛋白质-蛋白质相互作用(PPI)网络的构建;再使用Bioconductor平台和R软件进行GO功能富集分析和KEGG通路富集分析。结果:筛选得到雷公藤有效成分共22个,作用靶点413个,从GEO数据库确定干燥综合征差异基因466个;有效化合物-干燥综合征网络总共包括28个节点和41条相互作用关系,关键活性化合物有山柰酚、川陈皮素、β-谷甾醇、雷公藤内酯醇、浙贝素等;通过蛋白质-蛋白质相互作用(PPI)网络得到11个核心蛋白;GO富集分析主要涉及共获得生物过程(BP)295个,细胞组成(CC)3个,分子功能(MF)46个;相关条目主要涉及花生四烯酸代谢、类二十烷酸、脂肪酸、前列腺素等生物的合成与代谢过程、氧化应激以及多种酶的活性等;KEGG通路富集筛选得到19条信号通路,主要包括为花生四烯酸代谢、血清素能突触、TNF信号通路、多种细胞凋亡、VEGF信号通路、IL-17信号通路、核因子-κB信号通路等。结论:本研究应用网络药理学方法,对雷公藤治疗干燥综合征的活性成分、作用靶点和信号通路进行了探索性研究,发现雷公藤中的山柰酚、川陈皮素、β-谷甾醇等活性成分可参与调节花生四烯酸、类二十烷酸、脂肪酸、前列腺素等生物的合成与代谢过程、氧化应激以及多种酶的活性,并通过血清素能突触、TNF信号通路、多种细胞凋亡通路、VEGF信号通路、IL-17信号通路、核因子-κB信号通路等信号通路进行综合靶向调控,从而发挥治疗作用。

Mechanism Study of Tripterygium Wilfordii on Sjogren's Syndrome Based on Network Pharmacology

Objective:To explore the association and potential mechanism of Tripterygium wilfordii and Sjogren′s syndrome based on network pharmacology.Methods:By searching the TCMSP database,combined with oral bioavailability and drug-like analysis,the main active ingredients and action targets in Tripterygium wilfordii were screened;the GEO database was searched to screen for predicted targets for Sjogren′s syndrome,and effective compounds were mapped to disease targets;Cytoscape software was used to construct the target interaction network of Tripterygium compound-Sjogren′s syndrome;PPI protein interaction network was constructed through Bisogenet package;Bioconductor platform and R software were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis.Results:A total of 22 active ingredients of Tripterygium wilfordii were screened and 413 targets were identified.466 differential genes for Sjogren′s syndrome were identified from the GEO database;the effective compound-Sjogren′s syndrome network includes a total of 28 nodes and 41 interactions.The key active compounds are kaempferol,ligandrin,β-sitosterol,triptolide,and zhebein;11 core proteins were obtained through the PPI network;GO enrichment analysis mainly involved a total of 295 biological processes(BP),3 cell compositions(CC),and 46 molecular functions(MF);relevant entries mainly involve arachidonic acid metabolism,eicosanoid acid,fatty acids,prostaglandins and other organisms,oxidative stress,and the activities of various enzymes,etc;KEGG pathway was enriched and screened to obtain 19 signaling pathways,including arachidonic acid metabolism,serotonergic synapses,TNF signaling pathway,a variety of apoptosis,VEGF signaling pathway,IL-17 signaling pathway,NF-κB signaling Pathways,etc.Conclusion:This study used the network pharmacology method to preliminarily analyze the multi-component,multi-target,and multi-path characteristics of Tripterygium wilfordii in treating Sjogren′s syndrome,providing a reference for the implementation of subsequent clinical and scientific research-related work.