摘要
基于UHPLC-Q-Exactive Orbitrap HRMS联合网络药理学及分子对接技术探究白及“异病同治”黄褐斑、胃肠道出血、肺癌和支气管-肺炎性病变的物质基础和分子机制。利用HPLC建立17批不同产地白及指纹图谱,进行相似度评价;进一步通过UHPLC-Q-Exactive Orbitrap HRMS分析,获得17批白及的共有化学成分;针对共有化学成分,根据生物利用度和类药性筛选活性成分,利用TCMSP和SwissTargetPrediction数据库获取白及活性成分的作用靶点。在DrugBank、TTD、GeneCards数据库中检索疾病相关靶点,绘制韦恩图,获得白及与疾病的共有靶点作为“异病同治”靶点;借助STRING数据库建立蛋白质相互关系,并在Bioconductor数据库中对“异病同治”靶点进行KEGG和GO分析;使用Cytoscape 3.7.2软件构建“白及化学成分-异病同治靶点”网络和蛋白-蛋白相互作用(PPI)网络,拓扑分析筛选出关键活性成分和核心靶点;最后,运用AutoDock Vina 1.1.2软件对活性成分与核心靶点进行分子对接验证。指纹图谱有13个共有峰,不同批次间指纹图谱的相似度在0.941~0.998。鉴定出白及的化学成分53个,17批白及的共有化学成分18个;网络药理学筛选到白及治疗4种疾病的药效物质基础是多糖类、联菲类、二氢菲类和联苄类等11个化合物,异病同治靶点42个,这些靶点参与细胞对化学应激的反应、活性氧的反应和蛋白激酶B信号转导的正调控等生物过程,涉及PI3K-Akt、ErbB、Rap1、FoxO、MAPK和雌激素等121条信号通路;分子对接显示关键活性成分与核心靶点亲和力好。该研究初步阐释了白及通过多成分、多靶点和多通路联合作用发挥治疗黄褐斑、胃肠道出血、肺癌和支气管-肺炎性病变的“异病同治”的作用,为其深入开发和应用提供了一定的理论基础。
Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking,the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma,gastrointestinal hemorrhage,lung cancer and bronchoplumonary inflammation as"homotherapy for heteropathy"were explored.The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC,and the similarity analysis was carried out.The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS.Depending on the bioavailability and drug-like properties of the common components,the active chemical components were screened,and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP)and SwissTargetPrediction database.The protein targets related to diseases were retrieved from the databases DrugBank,TTD and GeneCards to produce a Venn diagram.The shared targets were obtained between drugs and diseases as"homotherapy for heteropathy"targets.The protein-protein interaction(PPI)was analyzed with the STRING database,and KEGG and GO analyses of the"homotherapy for heteropathy"targets were performed using the Bioconductor database.Cytoscape 3.7.2 software was employed to construct the"chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets"network and PPI network,and topological analysis was conducted to screen out the key active chemical components and core targets.Finally,the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6,which verified the interaction between them.Thirteen common peaks were identified by fingerprint chromatography,and the similarity between different batches was 0.941-0.998.Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma,and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma.Network pharmacologic screening s
作者
刘春花
付昌丽
孙佳
陆苑
潘洁
李勇军
王永林
黄勇
潘卫东
LIU Chun-hua;FU Chang-li;SUN Jia;LU Yuan;PAN Jie;LI Yong-jun;WANG Yong-lin;HUANG Yong;PAN Wei-dong(Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine(Ministry of Education),Guizhou Medical University,Guiyang 550004,China;School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550004,China;Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University,Guiyang 550004,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第13期3552-3565,共14页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(U1812403)
中央引导地方科技发展专项(黔科中引地[2018]4006)
贵州省高层次创新型人才项目(黔科合平台人才-GCC[2022]031-1)
贵阳市科技计划项目(筑科合同[2024]2-35号)。
关键词
白及
指纹图谱
成分分析
网络药理学
异病同治
分子对接
Bletillae Rhizoma
fingerprint chromatography
component identification
network pharmacology
homotherapy for heteropathy
molecular docking
