基于网络药理学和分子对接技术探讨“桑白皮-茯苓皮-香加皮”治疗心力衰竭的作用机制  

Mechanism of "Cortex Mori Radicis-Poria Peels-Periploca Sepium" in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking

作　　者：连妍洁 周明学[2] 刘红旭[3] 佟彤[3] 来晓磊[3] 邢文龙[3] LIAN Yanjie;ZHOU Mingxue;LIU Hongxu;TONG Tong;LAI Xiaolei;XING Wenlong(Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学,北京100069 [2]北京市中医研究所 [3]首都医科大学附属北京中医医院,北京100010

出　　处：《中西医结合心脑血管病杂志》2023年第13期2321-2331,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家中医药管理局中医药循证能力建设项目-专科专病循证能力提升(No.2019XZZX-XXG001);北京市医院管理局重点医学专业发展计划项目(No.ZYLX201817)。

摘　　要：目的:基于网络药理学方法探讨“桑白皮-茯苓皮-香加皮”治疗心力衰竭(心衰)的作用机制。方法:利用中药系统药理学技术平台数据库(TCMSP)获取桑白皮、香加皮主要化学成分及作用靶点,利用PubChem数据库、SwissTarget Prediction数据库获取茯苓皮作用成分及靶点;基于利用UniProt数据库对获取的作用靶点进行规范化处理;通过GeneCards、OMIM、DisGeNET、TTD、DrugBank、HERB、MalaCards数据库获取心衰相关靶点;利用Venny 2.1.0绘图网站构建Venn图,得到“桑白皮-茯苓皮-香加皮”与心衰的交集靶点;应用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络;通过Metascape数据库对交集靶点进行基因本体(GO)功能及京都基因和基因组百科全书(KEGG)通路富集分析,使用微生信网站绘制结果气泡图,相关结果采用Cytoscape 3.7.2软件进行可视化研究及网络拓扑结构分析。使用AutoDock Tools 1.5.6进行分子对接研究。结果:经过数据库分析共筛选出“桑白皮-茯苓皮-香加皮”活性成分62个,潜在作用靶点404个,其中涉及治疗心衰的靶点99个。通过GO功能富集分析得到1 639个生物进程条目、124条分子功能条目及57类细胞成分条目。通过KEGG通路富集分析得到175条与心衰相关的通路。分子对接结果显示槲皮素、山柰酚与核心靶点前列腺素内环氧化物合成酶2(PTGS2)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)、白细胞介素-1β(IL-1β)均有较强的氢键作用。结论:通过“中药-成分-疾病靶点-通路”网络显示,槲皮素、山柰酚、三萜类化合物是“桑白皮-茯苓皮-香加皮”治疗心衰的主要活性成分,其对应的核心靶点如PTGS2、IL-6、TNF、VEGFA、IL-1β等可能协同作用于脂质与动脉粥样硬化信号通路、缺氧诱导因子-1α(HIF-1α)信号通路及核转录因子κB(NF-κB)通路等治疗心衰。分子对接结果进一步验证了主要化合�Objective:To explore the mechanism of "Cortex Mori Radicis-Poria peels-Periploca sepium" in the treatment of heart failure based on network pharmacology.Methods:The main chemical constituents and their targets of Cortex mori and Periploca sepium were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database.The active components and targets of Poria cocos peels were obtained by PubChem database and SwissTarget Prediction database.The target was normalized based on Uniprot database.The target of heart failure was obtained from GeneCards,OMIM,DisGeNET,TTD,DrugBank,HERB,and MalaCards databases.Venn diagram was constructed by Venny 2.1.0 mapping website,and the intersection target of "Cortex Mori Radicis-Poria peels-Periploca sepium" and heart failure was obtained.Protein-protein interaction(PPI) network was constructed using STRING platform.Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the intersection targets through Metascape database,and the resulting bubble map was drawn on the wechat bioinformatics website.Cytoscape 3.7.2 software was used for the visualization research and network topology analysis.AutoDock Tools 1.5.6 was used for molecular docking study.Results:A total of 62 active components were screened by database analysis,including 404 potential targets,99 of which were related to the treatment of heart failure.Through GO functional enrichment analysis,1 639 biological process items,124 molecular function items,and 57 types of cell components items were obtained.One hundred and seventy-five pathways related to heart failure were identified by KEGG pathway enrichment analysis.The molecular docking results showed that quercetin and kaigol showed strong hydrogen bonding with the core targets[prostaglandin-endoperoxide synthase 2(PTGS2),interleukin-6(IL-6),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA),and interleukin-1β(IL-1β)].Conclusion:Quercetin,kaempf

关 键 词：心力衰竭 网络药理学 分子对接技术 五皮饮 桑白皮 茯苓皮 香加皮 

分 类 号：R285[医药卫生—中药学]