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基于网络药理学探究三棱–莪术治疗甲状腺结节的作用机制
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Abstract:
目的：采用网络药理学方法研究三棱与莪术干预甲状腺结节的作用机理。方法：检索TCMSP数据库获取三棱与莪术的活性成分，再利用Uniprot数据库获得三棱与莪术标准化的靶点数据。借助Genecard数据库以及OMIM数据库查询收集甲状腺结节的相关靶点数据，并通过韦恩图平台获得甲状腺结节与三棱、莪术之间的共同基因。通过Cytoscape软件建立三棱、莪术活性成分–靶点网络信息图谱，并使用STRING数据库构建PPI网络模型，进而对关键靶点开展GO功能富集分析和KEGG通路富集分析。结果：三棱–莪术药对筛选得出5个有效活性成分，药物靶点69个。甲状腺结节疾病相关靶点4267个，疾病与药物交集靶点44个。PPI网络模型分析得到三棱–莪术治疗甲状腺结节以PTGS2、PPARG、BCL2、CASP3、ESR1为核心靶点。GO功能富集分析结果表明，潜在治疗靶点主要介入了对雌二醇的应答、低氧反应、核受体介导的信号通路等生物过程；KEGG通路富集分析显示，三棱–莪术干预甲状腺结节所涉及到的通路主要涵盖p53信号通路、甲状腺激素信号通路、IL-17信号通路、PI3K-Akt信号通路等。结论：三棱–莪术药对可依靠若干靶点以及多条通路的协同效应，实现对甲状腺结节的治疗作用。
Objective: To explore the mechanism by which Sanleng (Sparganium stoloniferum) and Ezhu (Curcuma phaeocaulis) intervene in thyroid nodules using a network pharmacology approach. Methods: Active components of Sanleng and Ezhu were retrieved from the TCMSP database, and their standardized target data were subsequently obtained from the UniProt database. The Genecards and OMIM databases were searched to collect target information associated with thyroid nodules, and a Venn diagram platform was used to identify common genes shared between thyroid nodule targets and those of Sanleng and Ezhu. Cytoscape software was employed to construct an active component-target network map for the two herbs, and the STRING database was utilized to build a protein-protein interaction (PPI) network model. GO functional enrichment analysis and KEGG pathway enrichment analysis were then conducted on the key targets. Results: Screening of the Sanleng-Ezhu herb pair identified 5 effective active components and 69 drug-related targets. A total of 4267 disease-related targets for thyroid nodules were found, with 44 overlapping targets between the disease and the herbs. PPI network analysis indicated that the core therapeutic targets of Sanleng-Ezhu for treating thyroid nodules are PTGS2, PPARG, BCL2, CASP3, and ESR1. GO functional enrichment analysis showed that the potential therapeutic targets are primarily involved in biological processes such as response to estradiol, response to hypoxia, and nuclear receptor-mediated signaling pathway; KEGG pathway enrichment analysis revealed that the pathways implicated in Sanleng-Ezhu intervention in thyroid nodules mainly include the p53 signaling pathway, thyroid hormone signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway, among others. Conclusion: The
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