摘要
目的通过网络药理学、分子对接和分子动力学方法研究杜仲-淫羊藿药对治疗骨质疏松的作用机制。方法查询中药系统药理学数据库与分析平台(TCMSP)和相关文献筛选杜仲-淫羊藿药对的活性成分, 应用TargetNet、SwissTargetPrediction、STITCH数据库筛选活性成分的作用靶点, 应用GeneCards、OMIM、TTD、DisGeNET数据库筛选骨质疏松的相关靶点, 利用Venny 2.1.0在线工具获取交集靶点。应用STRING数据库进行蛋白质-蛋白质相互作用(PPI)分析。使用Cytoscape 3.8.2软件构建网络图并进行网络特征分析以确定核心成分和关键靶点。使用R 3.6.3软件进行基因本体(GO)功能注释及京都基因和基因组百科全书(KEGG)信号通路分析。使用SYBYL-X 2.1.1软件将核心成分与关键靶点进行分子对接。使用GROMACS 2021.6软件进行分子动力学模拟。结果筛选出杜仲-淫羊藿药对的活性成分47个, 作用靶点329个, 骨质疏松的相关靶点4 604个, 交集靶点210个。网络特征分析表明木犀草素、槲皮素、山柰酚、咖啡酸、金圣草黄素、松脂素是核心成分, 蛋白激酶B1(Akt1)、白细胞介素-6(IL-6)、类固醇受体辅激活因子(Src)、含半胱氨酸的天冬氨酸蛋白水解酶-3(CASP3)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、前列腺素内过氧化物合酶2(PTGS2)、丝裂原激活蛋白激酶8(MAPK8)、转录因子JUN是关键靶点。GO分析显示生物过程(BP)主要涉及细胞激素代谢过程、细胞内受体信号通路、对氧化应激的反应、激素代谢过程等, 细胞组分(CC)主要涉及膜筏、膜微结构域、膜区、转录因子复合体等, 分子功能(MF)主要涉及核受体活性、转录因子活性、类固醇激素受体活性、激素结合等。KEGG分析表明"杜仲-淫羊藿"药对治疗骨质疏松的信号通路主要有破骨细胞分化相关通路、磷脂酰肌醇3-激酶(PI3K)-Akt信号通路和MAPK信号通路等。分子对接显示核心�
Objective To explore the mechanism of Eucommiae Cortex-Epimedii Folium herbal pair in the treatment of osteoporosis through network pharmacology,molecular docking,and molecular dynamics methods.Methods Search the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and relevant literature to screen the active compounds of Eucommiae Cortex-Epimedii Folium herbal pair.Using TargetNet,SwissTargetPrediction,and STITCH databases to predict the target of active compounds.GeneCards,OMIM,TTD and DisGeNET databases were used to screen the related targets of osteoporosis,and the intersection targets were obtained by Venny 2.1.0 online tool.Using STRING database for protein-protein interaction(PPI)network analysis.Construct a network diagram using Cytoscape 3.8.2 software and perform network feature analysis to determine key targets and core compounds.Using R 3.6.3 software for gene ontology(GO)functional annotation and Kyoto Encyclopedia of genes and genomes(KEGG)signaling pathway analysis.Apply SYBYL-X 2.1.1 software to perform molecular docking between core compounds and key targets,and use GROMACS 2021.6 software for molecular dynamics simulation.Results Totally 47 active compounds,329 targets related to compounds,4604 targets related to osteoporosis,and 210 intersecting targets of Eucommiae Cortex-Epimedii Folium herbal pair were selected.Network feature analysis showed that luteolin,quercetin,kaempferol,caffeic acid,chryseriol,and pinoresinol were core compounds,while protein kinase B1(Akt1),interleukin-6(IL-6),steroid receptor coactivator(Src),cysteinyl aspartate specific proteinase-3(CASP3),epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),prostaglandin-endoperoxide synthase 2(PTGS2),mitogen-activated protein kinase 8(MAPK8),and JUN were key targets.GO analysis showed that biological process(BP)mainly involve cellular hormone metabolism,intracellular receptor signaling pathways,oxidative stress responses,hormone metabolism processes,etc.Cell component(CC)mainly involv
作者
王敏娟
王婷
翟西峰
李杨
曹磊
胡佳薇
Wang Minjuan;Wang Ting;Zhai Xifeng;Li Yang;Cao Lei;Hu Jiawei(Physical and Chemical Laboratory,Center for Disease Control and Prevention of Shaanxi Province,Xi’an 710054,China;Biomedicine Key Laboratory of Shaanxi Province,College of Life Sciences,Northwest University,Xi’an 710069,China;School of Pharmaceutical Sciences,Xi’an Medical University,Xi’an 710021,China)
出处
《国际生物医学工程杂志》
CAS
2024年第4期364-374,共11页
International Journal of Biomedical Engineering
基金
陕西省自然科学基础研究计划(2021JQ-935)。
关键词
网络药理学
分子对接
分子动力学
杜仲
淫羊藿
骨质疏松
Network pharmacology
Molecular docking
Molecular dynamics
Eucommiae Cortex
Epimedii Folium
Osteoporosis
