[关键词]
[摘要]
【目的】 以中医“异病同治”理论为依据,采用网络药理学及分子对接方法探究当归芍药散治疗子宫腺肌病(AM)、子 宫内膜异位症(EMs)、盆腔炎性疾病后遗症(SPID)的作用机制。【方法】 通过 TCMSP及 SwissTargetPrediction 数据库检索当归 芍药散组方药物的化学成分并获取靶点,通过 DrugBank、OMIM、GeneCards及 DisGeNET 数据库收集 AM、EMs、SPID相关 疾病靶点。利用Venny 2.1在线分析软件构建韦恩图,获取药物与疾病的共有靶点,借助Cytoscape 3.7.2构建“药物-活性成 分-共有靶点”网络。利用 STRING 及 Cytoscape 3.7.2构建蛋白互作网络并分析其分子生物学机制,并结合 BioGPS获取关键 靶标的组织定位,利用DAVID数据库对交集靶点进行GO功能和KEGG通路富集分析,最后进行分子对接验证。【结果】 筛选 出当归芍药散活性成分 39个,潜在作用靶点 529个,与 3种疾病的共有靶点 60个。对共有靶点富集分析发现,当归芍药散 治疗AM、EMs及SPID的机制可能与参与调节癌症途径、PI3K/Akt信号通路、HIF-1信号通路、TNF信号通路等有关。分子 对接结果表明,药物主要活性成分分别与核心靶点结合并展现出较稳定的构象。【结论】 当归芍药散治疗子宫腺肌病、子宫 内膜异位症与盆腔炎性疾病后遗症涉及(+)-儿茶素、山柰酚、β-谷甾醇等多种化合物,通过多脏器作用于 TNF、EGFR、 PTGS2、HIF1A 等关键靶点,参与炎症反应、免疫调节、血管生成、细胞信号传导等多条信号通路,从而发挥对 3 种疾病 “异病同治”作用。
[Key word]
[Abstract]
Objective To investigate the mechanisms of Danggui Shaoyao San(DSS) in treating adenomyosis (AM),endometriosis(EMs),and sequelae of pelvic inflammatory disease(SPID) through network pharmacology and molecular docking, guided by the traditional Chinese medicine(TCM) principle of “same treatment for different diseases”. Methods Chemical components of DSS were retrieved from the TCMSP and SwissTargetPrediction databases,and their targets were identified. Disease targets for AM,EMs,and SPID were collected from DrugBank,OMIM,GeneCards,and DisGeNET. A Venn diagram was constructed using Venny 2.1 to identify common targets between DSS and the diseases. A “drug-active component-shared target” network was established via Cytoscape 3.7.2. Protein-protein interaction(PPI) networks were analyzed using STRING and Cytoscape 3.7.2 to explore molecular mechanisms. Key targets were localized to tissues using BioGPS. Functional enrichment analysis of GO terms and KEGG pathways was performed via DAVID,followed by molecular docking validation. Results Thirty-nine active components and 529 potential targets of DSS were identified,with 60 shared targets across the three diseases. Enrichment analysis revealed that DSS treats AM,EMs and SPID by modulating cancer-related pathways, the PI3K/Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway. Molecular docking demonstrated stable binding conformations between DSS’s primary active components and core targets. Conclusion DSS treats AM,EMs and SPID through multiple compounds [e.g.,(+)-catechin, kaempferol,β-sitosterol] acting on key targets(TNF,EGFR,PTGS2,HIF1A) across various organs,modulating inflammation, immune response, angiogenesis, and cell signaling pathways, thereby exerting its “same treatment for different diseases”effect.
[中图分类号]
R285
[基金项目]
国家自然科学基金委员会面上项目(编号:82274567);北京中医药大学东直门医院横向课题(编号:HX-DZM-202404)