基于网络药理学、分子对接研究肉苁蓉-淫羊藿-骨碎补治疗骨质疏松的作用机制

Mechanism of Herba Cistanches-Epimedium Herb-Fortune's Drynaria Rhizome in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

目的采用网络药理学方法研究肉苁蓉-淫羊藿-骨碎补对骨质疏松的作用机制。方法采用中药系统药理学数据库与分析平台(TCMSP)查找肉苁蓉-淫羊藿-骨碎补主要成分及靶点,采用Geen Cards数据库查找骨质疏松的靶基因。应用Venny2.1.0取基因交集,采用String数据库进行蛋白互作网络分析,Cytoscape构建活性-成分-靶点网络图,David数据库进行GO富集分析和KEGG通路分析,并进行分子对接。结果肉苁蓉-淫羊藿-骨碎补有效成分46种,与骨质疏松共同的靶点有225个,有效成分中suchilactone、quercetin、luteolin、kaempferol、eriodictyol、eriodyctiol、naringenin为核心成分,AKT1、ERS2、MMP-9、AR、mTOR为核心靶点;GO富集显示得到489个生物学过程(BP)、53个细胞组成(CC)、100个分子功能(MF)。KEGG结果显示得到癌症通路、PI3K-Akt信号通路、雌激素信号通路等149条。分子对接结果显示MMP-9与suchilactone、quercetin、luteolin、kaempferol能较好地结合。结论肉苁蓉-淫羊藿-骨碎补作用于骨质疏松是多靶点的,药物有效成分能从多途径调控骨质疏松相关靶标,治疗骨质疏松。

Objective To study the mechanism of herba cistanches-epimedium herb-fortune's drynaria rhizome on osteoporosis by network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to find the main components and targets of herba cistanches-epimedium herb-fortune's drynaria rhizome,and Geen Cards database was used to find the target genes of osteoporosis.Venny2.1.0 was used to take gene intersection,String database was used for protein interaction network analysis,Cytoscape was used to construct activity-component-target network diagram,David database was used for GO enrichment analysis and KEGG pathway analysis,and molecular docking was carried out.Results There were 46 effective components in herba cistanches-epimedium herb-fortune's drynaria rhizome,and 225 common targets with osteoporosis.suchilactone,quercetin,luteolin,kaempferol,eriodictyol,eriodyctiol and naringenin were the core components,AKT1,ERS2,MMP-9,AR and mTOR were the core targets.GO enrichment showed 489 biological processes(BP),53 cellular components(CC)and 100 molecular functions(MF).The results of KEGG showed that 149 cancer pathways,PI3K-Akt signaling pathways,estrogen signaling pathways and so on were obtained.The results of molecular docking showed that MMP-9 could bind to suchilactone,quercetin,luteolin and kaempferol well.Conclusion Herba cistanches-epimedium herb-fortune's drynaria rhizome has a multi-target effect on osteoporosis.The effective components of the drug can regulate osteoporosis-related targets from multiple pathways to treat osteoporosis.