广西医学

目的基于网络药理学和分子对接技术探讨当归四逆加吴茱萸生姜汤治疗子宫内膜异位症（EMT）的作用机制。方法通过中药系统药理学数据库与分析平台、PubChem数据库、SwissTargetPrediction数据库筛选当归四逆加吴茱萸生姜汤主要活性成分及其作用靶点，通过GeneCards®数据库、OMIM®数据库、DisGeNET数据库、DrugBank数据库搜索EMT的相关靶点，取两者交集即获得当归四逆加吴茱萸生姜汤治疗EMT的相关靶点。通过STRING数据库构建蛋白-蛋白相互作用（PPI）网络，采用Cytoscape 3.7.1软件进行拓扑分析，筛选出当归四逆加吴茱萸生姜汤治疗EMT的核心靶点。针对核心靶点，基于Metascape平台进行基因本体论功能富集分析、京都基因与基因组百科全书通路富集分析。应用AutoDock软件进行分子对接验证。结果共获得当归四逆加吴茱萸生姜汤主要活性成分189种，对应的作用靶点213个，EMT相关靶点1 009个，取两者交集可获得当归四逆加吴茱萸生姜汤治疗EMT的相关靶点84个。PPI网络拓扑分析显示，核心靶点为肿瘤坏死因子（TNF）、蛋白激酶B、白细胞介素（IL）⁃6、雌激素受体1、肿瘤抑癌蛋白p53、IL⁃1β。核心靶点主要涉及对激素的反应等生物过程，转录调控复合体等细胞组分，转录因子结合、DNA结合转录因子结合等分子功能，以及内分泌抵抗、IL⁃17信号通路、TNF信号通路等通路。分子对接结果显示，核心靶点均可与对应的活性成分自发结合，且结合较为稳定。结论当归四逆加吴茱萸生姜汤中的主要活性成分（山柰酚、槲皮素等）通过作用于核心靶点（TNF、IL⁃6等），调控TNF信号通路、IL⁃17信号通路、内分泌抵抗通路等信号通路，从而发挥治疗EMT的作用。

Objective To explore the mechanism of Danggui Sini plus Wuzhuyu Shengjiang Decoction for the treatment of endometriosis (EMT) based on network pharmacology and molecular docking technique. Methods The main active components and their effect targets of Danggui Sini plus Wuzhuyu Shengjiang Decoction were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, PubChem database, SwissTargetPrediction database. Targets related to EMT were retrieved from the databases of GeneCards®, OMIM®, DisGeNET, and DrugBank, and targets related to Danggui Sini plus Wuzhuyu Shengjiang Decoction for the treatment of EMT were obtained after acquiring intersection of the two. The protein⁃protein interaction (PPI) network was established by the STRING database. The Cytoscape 3.7.1 software was used to perform topological analysis for screening the core targets of Danggui Sini plus Wuzhuyu Shengjiang Decoction for treating EMT. For the core targets, the Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed based on the Metascape platform. The AutoDock software was applied to perform molecular docking validation. Results A total of 189 main active components of Danggui Sini plus Wuzhuyu Shengjiang Decoction were obtained, their corresponding effect targets were 213, targets related to EMT were 1009, and 84 targets related to Danggui Sini plus Wuzhuyu Shengjiang Decoction for the treatment of EMT were obtained after acquiring intersection of the two. PPI network topological analysis revealed that the core targets were tumor necrosis factor (TNF), protein kinase B, interleukin (IL)⁃6, estrogen receptor 1, tumor suppressor protein p53, and IL⁃1β. The core targets were mainly involved in biological processes such as responses to hormones, in cellular compositions such as transcriptional regulatory complex, and in molecular functions such as transcription factors binding, DNA⁃binding transcription factors binding, as well as in pathways such as endocrine resistance, IL⁃17 signaling pathway, TNF signaling pathway. The results of molecular docking indicated that the core targets could spontaneously bind to the corresponding active components, and the binding was relatively stable. Conclusion The main active components (kaempferol and quercetin, etc.) of Danggui Sini plus Wuzhuyu Shengjiang Decoction regulate TNF signaling pathway, IL⁃17 signaling pathway, and endocrine resistant pathway, etc., so as to exert therapeutic effect of EMT through acting on the core targets (TNF and IL⁃6, etc.).