基于网络药理学与分子对接分析补肾疏肝方治疗多囊卵巢综合征作用机制
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R711.75;R285

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国家卫生健康委医药卫生科技发展项目(WKZX2024DN0133);广东省中医药局科研项目(202405061035417950)


Analysis of the Mechanism of Action of Bushen Shugan Prescription in the Treatment of Polycystic Ovary Syndrome Based on Network Pharmacology and Molecular Docking
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    摘要:

    目的:采用网络药理学和分子对接技术分析补肾疏肝方治疗多囊卵巢综合征(PCOS) 的作用机 制。方法:采用传统中药系统药理学数据库与分析平台(TCMSP) 检索补肾疏肝方的有效活性成分及关键靶 点,使用Gencards、OMIM、TTD及DrugBank数据库检索与PCOS相关的疾病靶点。通过Venny网络平台检索药 物和疾病之间的交集靶点。运用Cytoscape 3.10.2软件进行药方-活性成分-疾病交集靶点的网络构建及可视化。 通过STRING数据库得到药方-疾病交集靶点的蛋白质互作(PPI) 网络。运用ClusterProfiler数据库对全交集靶 点和核心靶点进行基因本体(GO) 功能和京都基因与基因组百科全书(KEGG) 通路富集分析。借助 AutoDock-Vina软件对药物关键活性成分和疾病的核心靶点进行分子对接。最后,使用Pymol和PLIP将结果可 视化。结果:共筛选出补肾疏肝方活性成分161个,有效活性成分作用靶点286个,度值前10的活性成分为槲 皮素、山奈酚、木犀草素、异鼠李素、β-谷甾醇、甲氧异黄酮、7-甲氧基-2-甲基异黄酮、类黄酮、脱水淫羊 藿黄素、豆甾醇。PCOS的疾病靶点4 632个,补肾疏肝方-PCOS的交集靶点共194个。筛选出PTGS2、ESR2、 AR、NOS2、NCOA2、PRSS1、PPARG、CDK2、GSK3β、PTGS1等10个核心靶点。通过GO分析,共得到786个 生物过程(BP),11个细胞组分(CC),63个分子功能(MF)。通过KEGG通路富集分析,主要涉及卡波西 肉瘤相关疱疹病毒感染、脂质与动脉粥样硬化、乙型肝炎病毒、糖尿病并发症中的晚期糖基化终未产物与其受 体(AGE-RAGE)、人巨细胞病毒感染等信号通路。分子对接结果显示主要有效活性成分与核心靶点之间亲和 力高。结论:补肾疏肝方中的槲皮素、山奈酚、木犀草素等成分通过PTGS2、ESR2、AR等靶点作用于卡波西 肉瘤相关疱疹病毒感染、脂质与动脉粥样硬化、乙型肝炎病毒、糖尿病并发症中的AGE-RAGE等信号通路治 疗PCOS。

    Abstract:

    Abstract: Objective: To analyze the mechanism of action of Bushen Shugan Prescription in the treatment of polycystic ovary syndrome(PCOS) using network pharmacology and molecular docking techniques. Methods: The effective active components and key targets of Bushen Shugan Prescription were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease targets related to PCOS were searched using GeneCards, OMIM, TTD, and DrugBank databases. Intersection targets between the medicine and disease were identified through the Venny web platform. A network of prescription-active components-disease intersection targets was constructed and visualized using Cytoscape 3.10.2 software. The protein-protein interaction (PPI) network of prescription-disease intersection targets was obtained from the STRING database. Gene Ontology (GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of all intersection targets and core targets were performed using the ClusterProfiler database. Molecular docking of key active components of the medicine and key disease targets was conducted using AutoDock-Vina software. Finally,the results were visualized using PyMOL and PLIP. Results: A total of 161 active components of Bushen Shugan Prescription were identified, with 286 targets for the active components. The top 10 active components by degree value were quercetin,kaempferol, luteolin, isorhamnetin, β- sitosterol, formononetin, 7-methoxy-2-methylisoflavone, naringenin, anhydroicaritin, and stigmasterol. There were 4 632 disease targets for PCOS, and 194 intersection targets between Bushen Shugan Prescription and PCOS. Ten core targets were identified,including PTGS2,ESR2,AR,NOS2,NCOA2,PRSS1, PPARG,CDK2,GSK3β,and PTGS1. GO analysis yielded 786 biological processes(BP),11 cellular components (CC), and 63 molecular functions(MF). KEGG pathway enrichment analysis mainly involved pathways such as Kaposi's sarcoma-associated herpesvirus infection, lipid and atherosclerosis, hepatitis B virus, AGE-RAGE in diabetic complications,and human cytomegalovirus infection. Molecular docking results showed strong affinity between the main active components and core targets. Conclusion:Active components in Bushen Shugan Prescription,such as quercetin,kaempferol,and luteolin,act on targets like PTGS2,ESR2,and AR,and are involved in pathways such as Kaposi's sarcoma-associated herpesvirus infection,lipid and atherosclerosis,hepatitis B virus,and AGE-RAGE in diabetic complications to treat PCOS.

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范杏韵,张梦歌,宫喜双.基于网络药理学与分子对接分析补肾疏肝方治疗多囊卵巢综合征作用机制[J].新中医,2025,57(17):194-201

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  • 在线发布日期: 2025-09-05
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