基于网络药理学和分子对接探讨苗药黑骨藤治疗阿尔茨海默病的作用机制  

Action mechanism of Periploca forrestii in against Alzheimer's disease based on network pharmacology and molecular docking

作　　者：舒燕霞 郭江涛 徐文芬 张永萍 孙开芬 石兴雨 曾令琴 SHU Yan-Xia;GUO Jiang-Tao;XU Wen-Fen(School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]国家苗药工程技术研究中心 [3]贵州中药炮制与制剂工程技术研究中心

出　　处：《中国老年学杂志》2023年第22期5484-5492,共9页Chinese Journal of Gerontology

基　　金：国家自然科学基金委员会-贵州省人民政府联合基金(U1812403-2);贵州省科技基金项目(黔科合基础[2020]1Y372)。

摘　　要：目的运用网络药理学及分子对接技术,探究苗药黑骨藤治疗阿尔茨海默病(AD)的活性成分和潜在作用机制。方法通过文献搜集苗药黑骨藤的化学成分,利用中药系统药理学数据库(TCMSP)和Swiss ADME数据库筛选黑骨藤的主要活性成分,采用Swiss Target Prediction和SEA数据库预测活性成分的作用靶点。通过GeneCards、OMIM数据库检索AD相关靶点,经Venny2.1.0获取成分-疾病交集靶点,结合STRING数据库和Cytoscape3.8.0软件对交集靶点进行蛋白互作(PPI)网络分析。再借助HIPLOT数据库对交集靶点进行基因本体(GO)分析和基因组百科全书(KEGG)信号通路富集分析。最后,利用AutoDock Tools1.5.6软件将潜在成分与核心靶点进行分子对接。结果苗药黑骨藤的活性成分共24个,对应靶点574个,1513个AD靶点,交集靶点159个;GO分析得到2661条生物过程,587条分子功能,311条细胞成分;KEGG分析得到AD主要参与神经退行性疾病-多发性疾病途径、卡波西肉瘤相关疱疹病毒感染、癌症中的蛋白多糖等相关通路。分子对接结果显示,山柰酚、槲皮素、汉黄芩素、丹参酮ⅡA、杠柳苷元等与类固醇受体辅助活化因子(SRC)、丝裂原活化蛋白激酶(MAPK)3、血管内皮生长因子(VEGF)A蛋白等具有较强结合能力。结论通过成分-靶点-通路网络及分子对接验证,筛选出黑骨藤抗AD的有效成分,并探究其抗AD作用机制,为苗药黑骨藤抗AD的新药开发和应用提供思路和理论依据。Objective To explore the active ingredients and potential mechanism of Periploca forrestii in the treatment of Alzheimer's disease(AD)by network pharmacology and molecular docking technique.Methods The chemical constituents of the Periploca forrestii were collected through literature retrieval.The main active components of Periploca forrestii were screened by using traditional Chinese medicine system pharmacology database(TCMSP)and Swiss ADME database,and the action targets of active components were predicted by Swiss Target Prediction and SEA database.Targets related AD were retrieved by GeneCards and OMIM databases,drug-disease intersection targets were obtained by Venny2.1.0.Protein interaction(PPI)network analysis of intersection targets was performed by combining STRING database with Cytoscape3.8.0 software.Then HIPLOT database was used for gene ontology(GO)analysis,and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway enrichment analysis of intersection targets.Finally,AutoDock Tools1.5.6 software was used to carry out molecular docking for potential components and core targets.Results The Periploca forrestii had 24 active components,574 corresponding targets,1513 related AD targets,and 159 intersection targets were obtained.GO analysis obtained 2661 biological process,587 molecular function,311 cell components.KEGG analysis showed that AD was mainly participate in pathways of neurodegeneration-multiple diseases,Kaposi sarcoma associated herpes virus infection,cancer proteoglycan pathways and other related pathways.The molecular docking showed that kaempferol,quercetin,Wogonin,TanshinoneⅡA and periplogenin had strong binding ability to steroid receptor coactivator(SRC),mitogen-activated protein kinase(MAPK)3 and vascular endothelial growth factor(VEGF)A.Conclusions Through the component-target-pathway network and molecular docking validation,the active components of Periploca forrestii against AD were screened,its mechanism of action against AD were explored,could provide ideas and theoretical b

关 键 词：黑骨藤 网络药理学 分子对接 阿尔茨海默病 

分 类 号：R285[医药卫生—中药学]