[关键词]
[摘要]
探讨桂枝茯苓丸治疗多囊卵巢综合征(PCOS)和子宫内膜异位症(EMT)的异病同治作用机制。【方法】利用 TCMSP获取桂枝茯苓丸组成中药的活性成分及相关靶点。通过GeneCards、PharmGKB、TTD数据库分别筛选PCOS和EMT疾 病靶点。使用R软件中的Venn R包获取药物与疾病的交集靶点后绘制Venn图,在Cytoscape中制作药物-活性成分-潜在靶点 互作网络图,STRING平台中绘制交集靶点蛋白互作网络(PPI)图,Cytoscape对PPI网络进行优化并筛选核心靶点。应用R语 言进行基因本体论(GO)富集和京都基因与基因组百科全书(KEGG)富集分析,AutoDockTools进行分子对接。【结果】获得桂 枝茯苓丸85个活性成分及191个相应靶点,桂枝茯苓丸治疗PCOS、EMT的潜在靶点77个。桂枝茯苓丸治疗PCOS、EMT的 核心活性成分为槲皮素、β-谷甾醇、山柰酚、常春藤皂苷元、黄芩素,核心靶点为AKT1、EGFR、IL-6、TNF、TP53。GO 功能分析获得2 020个生物过程、34个细胞成分、126个分子功能,KEGG富集分析得到165条信号通路。分子对接显示该方 中核心成分与靶点对接良好。【结论】桂枝茯苓丸可能通过槲皮素、β-谷甾醇、山柰酚、常春藤皂苷元、黄芩素,调节脂质 和动脉粥样硬化、AGE-RAGE信号通路、流体剪切应力和动脉粥样硬化、化学致癌-受体激活等信号通路,作用于靶点 AKT1、EGFR、IL-6、TNF、TP53,从而“异病同治”PCOS和EMT。
[Key word]
[Abstract]
To investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT). Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills. GeneCards, PharmGKB, and TTD databases were used to screen PCOS and EMT disease targets,respectively. The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI) network diagram was drawn in the STRING platform, and Cytoscape was used to optimize the PPI network and screen the core targets. R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, and AutoDockTools was for molecular docking. Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT. The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin, baicalein, and the core targets were AKT1, EGFR, IL-6, TNF, and TP53. GO functional analysis yielded 2 020 biological process, 34 cellular components, 126 molecular functions, and KEGG enrichment analysis yielded 165 signaling pathways. Molecular docking showed that the core components in the formula docked well with the targets. Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis, AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, and chemical carcinogenesis-receptor activation through quercetin, β- sitosterol, kaempferol, hederagenin, and baicalein, and act on AKT1, EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金青年项目(编号:82004395);广东省中医药局科研课题资助项目(编号:20212203);深圳市科技创新委员会 面上项目(编号:20210319124337003)