摘要
目的 通过数据挖掘、网络药理学和分子对接方式探讨补肾法治疗失眠的核心组方及其作用机制.方法 收集知网、万方、维普数据库中自建库以来至 2022 年 10 月 24 日有关补肾法治疗失眠的相关文献.分别运用Microsoft Excel、IBM SPSS Modeler18.0、Cytoscape3.7.1、Origin2021 软件进行频次统计、关联规则分析、复杂网络图构建、聚类分析,获得核心药物组方.通过TCMSP 数据库获得核心组方相关成分靶点,运用GeneCards、OMIM、DrugBank数据库分析疾病相关靶点,取交集后通过STRING数据库和Cytoscape 3.7.1 构建PPI网络,通过Metascape数据库进行GO富集分析和KEGG通路富集分析,构建活性成分-靶点网络.采用AutodockVina 1.2.3 进行分子对接,预测活性成分和核心靶点的结合性能.结果 本次研究共录入130 张中药处方,涉及中药 134 味,总使用频次1 572 次,药性药味以平、甘为主,归经以肝、心、肾经为主,综合分析得出核心组方为酸枣仁、山茱萸、当归、熟地黄和首乌藤.核心组方有效成分 46 种,靶点 134 个,疾病靶点 3 236 个,交集靶点73 个,其中核心靶点为白细胞介素 6(IL6)、肿瘤坏死因子(TNF)、白细胞介素 1β(IL1β)、血管内皮生长因子A(VEGFA)、前列腺素内过氧化物合酶 2(PTGS2)、肿瘤蛋白p53(TP53)、一氧化氮合酶3(NOS3)等.GO功能富集分析结果显示,生物功能 1 037 条,细胞组分 55 条,分子功能125 条.KEGG通路富集分析141 条,主要包括神经活性配体-受体相互作用等.选取核心成分和靶点进行分子对接模拟,43 对配体受体组合对接结构稳定.结论 基于补肾法治疗失眠的核心处方为酸枣仁、山茱萸、熟地黄、首乌藤和当归,治疗失眠的机制可能与调控炎症反应、细胞凋亡、神经递质及血管内皮功能的相关因子和通路有关.
Abstract
Objective To explore the core formulas of tonifying kidney for insomnia and its mechanism by means of data mining,network pharmacology and molecular docking.Methods Relevant literature on tonifying kidney therapy for insomnia was collected from Zhichou,Wanfang,and VIP,up to October 24,2022.Microsoft Excel,IBM SPSS Modeler18.0,Cytoscape3.7.1,and Origin2021 were employed for frequency statistics,association rule analysis,construction of complex network diagrams,cluster analysis.The core drug formulations were obtained.The TCMSP database provided related component targets of the core formula,and disease-related targets were analyzed using GeneCards,OMIM,and DrugBank databases.After obtaining the intersection,a PPI network was constructed using the STRING database and Cytoscape 3.7.1.GO enrichment analysis and KEGG pathway enrichment analysis were performed through the Metascape database to build the active ingredient-target network.Molecular docking was conducted using AutodockVina 1.2.3 to predict the binding performance of active ingredients and core targets.Results A total of 130 prescriptions were included,involving 134 herbs with a total frequency of use of 1,572 times.The main medicinal properties were flat and sweet,and the channels targeted were primarily liver,heart,and kidney channels.The core formula consisted of Suanzaoren(Semen Ziziphi Spinosae),Shanzhuyu(Fructus Corni),Danggui(Radix Angelicae Sinensis),Shudihuang(Radix Rehmanniae Praeparata),and Shouwuteng(Caulis Polygoni Multiflori).There were 46 active ingredients in the core formula,134 targets,and 3,236 disease-related targets,with 73 intersection targets.Core targets included IL6,TNF,IL1β,VEGFA,PTGS2,TP53,NOS3,etc.GO functional enrichment analysis covered 1,037 biological functions,55 cellular components,and 125 molecular functions.KEGG pathway enrichment analysis included 141 pathways,primarily involving neuroactive ligand-receptor interactions.Molecular docking simulations for core components and targets showed stable docking structures for 43 pairs of ligand-receptor combinations.Conclusion The core formula for treating insomnia through tonifying kidney therapy includes Suanzaoren,Shanzhuyu,Shudihuang,Shouwuteng,and Danggui.The mechanism of treating insomnia may be related to factors and pathways regulating inflammation,apoptosis,neurotransmitters,and vascular endothelial function.
基金项目
国家重点研发计划资助项目(2019YFC1710103)
深圳市"医疗卫生三名工程"项目资助(SZZYSM202105010)
国家科技期刊平台
NSTL
万方数据