基于网络药理学探讨月泰贴脐方治疗排卵障碍性不孕症的作用机制  

Molecular Mechanism of Yuetai Tieqi Fang in Treatment of Ovulation Failure Infertility Based on Network Pharmacology

作　　者：覃楚悦 罗玺 詹燕珊 刘锐萍 王芳 时军 QIN Chuyue;LUO Xi;ZHAN Yanshan;LIU Ruiping;WANG Fang;SHI Jun(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006 Guangdong,China;Guangdong Engineering&Technology Research Center of Precise Drug Delivery System,Guangzhou 510006 Guangdong,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东省局部精准递药制剂工程技术研究中心,广东广州510006

出　　处：《中药新药与临床药理》2022年第5期674-681,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：全国中医药创新骨干人才培养项目(国中医药人教函[2019]128号)。

摘　　要：目的基于网络药理学方法探讨月泰贴脐方治疗排卵障碍性不孕症的作用机制,为该方研发及临床应用提供参考。方法运用中医药系统药理学平台(TCMSP)获取月泰贴脐方(延胡索、肉桂、当归、细辛、小茴香)的活性成分,PubChem数据库结合SwissTargetPrediction数据库获取相关药物靶点,GeneCards、DisGeNET和DRUGBANK数据库搜集排卵障碍性不孕症的相关疾病靶点,以Venny 2.1.0取交集靶点绘制韦恩图;交集靶点导入STRING v11数据库构建PPI网络并提取网络中的关键靶点;以Cytoscape 3.7.1软件构建“月泰贴脐方-活性成分-排卵障碍性不孕症靶点”网络,获得关键活性成分;以R 3.6.3软件对交集靶点进行GO分析和KEGG通路富集分析。通过AutoDockVina软件进行分子对接,并用动物实验进行药理学验证。结果月泰贴脐方中槲皮素等有效成分通过丝氨酸/苏氨酸激酶-1(AKT1)、表皮生长因子受体(EGFR)、SRC原癌基因(SRC)等靶点作用于卵巢类固醇生成和类固醇生物合成等通路,能提高血清促排卵素(FSH)、黄体生成素(LH)、雌二醇(E_(2))的含量,以发挥对排卵障碍性不孕症的治疗作用。结论初步揭示了月泰贴脐方调治排卵障碍性不孕症的多成分、多靶点、多通路的作用机制,可为其临床应用及研发提供理论基础。Objective The molecular mechanism of Yuetai Tieqi Fang(YTTQF)in the treatment of ovulation failure infertility was analyzed based on the network pharmacological method,to provide a reference for the development of new drugs and the clinical application of YTTQF.Methods Firstly,TCMSP database were searched to obtain all active chemical compositions of YTTQF(Corydalis rhizoma,Cinnamomi cortex,Angelicae sinensis radix,Asari radix et rhizoma,Foeniculif fructus),and the active targets of YTTQF were collected from PubChem and Swiss Target Prediction.Secondly,ideal targets of ovulation failure infertility were acquired through Genecards,DisGeNET and DRUGBANK databases,then the intersection targets were acquired and Venn diagram was drawn through Venny2.1.0 online website.Thirdly,the intersection targets were introduced into STRING v11 database to build a PPI network,and key proteins in the network were found.Then,the network of“drug-ingredients-disease targets”was constructed by Cytoscape 3.7.1 software,and the key ingredients were obtained.The gene ontology(GO)function enrichment analysis and KEGG pathway enrichment analysis were performed by R3.6.3 software.Finally,the molecular docking was carried out by AutoDock Vina,and animal experiment were conducted to verify the targets of key composition in YTTQF.Results Active ingredients including quercetin in YTTQF act on Ovarian steroidogenesis pathway and Steroid hormone biosynthesis pathway through proteins like AKT Serine/Threonine Kinase 1(AKT1),Epidermal Growth Factor Receptor(EGFR),SRC Proto-Oncogene,Non-Receptor Tyrosine Kinase(SRC),and so on,which could increase contents of Estradiol(E_(2)),Follicle-stimulating hormone(FSH)and Luteinizing hormone(LH),and further cure ovulation failure infertility.Conclusion This study preliminarily revealed the mechanism of YTTQF on treating ovulation failure infertility with multi-components,multi-targets and multi-pathways,and provided a basis for the clinical development and utilization of YTTQF.

关 键 词：月泰贴脐方 延胡索 槲皮素 网络药理学 排卵障碍性不孕症 靶点预测 

分 类 号：R285.5[医药卫生—中药学]