摘要
目的:运用网络药理学和分子对接方法,探讨“白芍-牡蛎”药对治疗多囊卵巢综合征(PCOS)的作用机制。方法:通过中药系统药理学数据库与分析平台、HERB和BATMAN-TCM数据库筛选并获取白芍、牡蛎的主要活性成分及其作用靶点;通过GeneCards数据库收集PCOS疾病靶点,获取“白芍-牡蛎”药对治疗PCOS的预测靶点,建立药物-成分-靶点-疾病网络;通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并采用Cytoscape软件进行可视化分析;使用DAVID数据库进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析;最后通过AutoDock软件进行分子对接,并采用PyMol软件进行可视化分析。结果:通过筛选,共得到15个活性成分,排序居前3位的核心成分为山柰酚、β-谷甾醇和(+)儿茶素;筛选得到71个潜在作用靶点,其中包含白细胞介素6(IL-6)、肿瘤坏死因子(TNF)和蛋白激酶B(Akt)1等11个核心靶点;GO富集分析主要集中于信号转导、膜整体组分和转录因子活性等方面;KEGG分析主要富集在磷脂酰肌醇3激酶-Akt(PI3K-Akt)通路及神经活性配体-受体相互作用等;分子对接结果显示,“白芍-牡蛎”药对主要活性成分与核心靶点具有较好的结合活性,构象稳定。结论:“白芍-牡蛎”药对可通过作用于IL-6、TNF和Akt1等靶点及PI3K-Akt等通路对PCOS的相关基因表达、蛋白合成进行调控,从而降低PCOS患者的黄体生成素水平,缓解疾病相关症状,即通过多成分、多靶点、多通路的作用模式对PCOS起到治疗作用。
OBJECTIVE:To explore the mechanism of“radix paeoniae alba-concha oyster”in the treatment of polycystic ovary syndrome(PCOS)by using network pharmacology and molecular docking method.METHODS:The main active components and targets of radix paeoniae alba and concha oyster were screened and obtained from traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),HERB and BATMAN-TCM databases.The disease targets of PCOS were collected by GeneCards,and the predicted targets of“radix paeoniae alba-concha oyster”drug pair in the treatment of PCOS were obtained,the drug-component-target-disease network was established.The protein-protein interaction(PPI)network was constructed by String database and visualized by Cytoscape software.DAVID database was used for gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis.The molecular docking experiment was verified by AutoDock software,and the visualization analysis was performed by PyMol software.RESULTS:Through screening,a total of 15 active components were obtained,and the top 3 core components were kaempferol,beta-sitosterol,(+)catechin.Totally 71 potential targets were screened,including 11 core targets such as interleukin 6(IL-6),tumor necrosis factor(TNF)and protein kinase B(Akt)1.GO enrichment analysis mainly focused on signal transduction,membrane components,transcription factor activities.KEGG analysis was mainly enriched in phosphatidylinositol 3 kinase-Akt(PI3K-Akt)pathway and neural active ligand-receptor interaction.Results of molecular docking showed that“radix paeoniae alba-concha oyster”had a good binding activity between the main active component and the core target,and the conformation was stable.CONCLUSIONS:“Radix paeoniae alba-concha oyster”can regulate the expression of PCOS related genes and protein synthesis by acting on targets such as IL-6,TNF,Akt1 and PI3K-Akt pathways,thereby reducing the LH value of PCOS patients and alleviating the d
作者
征征
郁悦
刘庭秀
杨靓靓
王裕星
刘新敏
ZHENG Zheng;YU Yue;LIU Tingxiu;YANG Liangliang;WANG Yuxing;LIU Xinmin(Dept.of Gynecology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Graduate School,China Academy of Chinese Medical Sciences,Beijing 100091,China;Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China;Dept.of Internal Medicine,the Second Affiliated Hospital of Dalian Medical University,Liaoning Dalian 116023,China)
出处
《中国医院用药评价与分析》
2023年第11期1288-1293,共6页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
国家自然科学基金项目(No.81674011)
中国中医科学院科技创新工程重大攻关项目(No.CI2021A02404)。
关键词
网络药理学
分子对接
白芍-牡蛎
多囊卵巢综合征
信号通路
作用机制
Network pharmacology
Molecular docking
Radix paeoniae alba-concha oyster
Polycystic ovary syndrome
Signaling pathway
Mechanism of action
