基于网络药理学和药效实验探究当归贝母苦参丸加味治疗慢性前列腺炎作用机理  

Mechanism of Modified Danggui Beimu Kushen Pills(当归贝母苦参丸)in the Treatment of Chronic Prostatitis Based on Network Pharmacology and Pharmacodynamic Experiment

作　　者：刘桂敏 汤轶波 于淑俊 佟科锦 王帅强 沈真如 刘丹 刘柘君 唐田 刘振权[1] LIU Guimin;TANG Yibo;YU Shujun;TONG Kejin;WANG Shuaiqiang;SHEN Zhenru;LIU Dan;LIU Zhejun;TANG Tian;LIU Zhenquan(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]北京中医药大学中医学院,北京100029

出　　处：《中药药理与临床》2023年第5期22-31,共10页Pharmacology and Clinics of Chinese Materia Medica

基　　金：北京中医药大学纵向发展基金(编号:2018-zxfzjj-002、81373780)。

摘　　要：目的:基于网络药理学及分子对接技术加以药效实验探究当归贝母苦参丸加味治疗慢性前列腺炎(CP)的作用机制。方法:通过中药系统药理分析平台(TCMSP)、中医药综合数据库(TCMID)和文献挖掘获得当归贝母苦参丸加味活性成分;运用SwissTargetPrediction数据库进行活性成分靶点预测,同时对TCMSP数据库成分已有靶点加以补充;运用在线孟德尔人类遗传数据库(OMIM)、GeneCards数据库、美国国家生物技术信息中心(NCBI)数据库收集CP相关靶点;运用Cytoscape软件构建中药-活性成分-靶点-通路网络图;运用STRING数据库进行生信分析,构建靶点蛋白-靶点蛋白互作(PPI)网络图,运用CytoNCA筛选核心靶点,并用Cytoscape进行可视化网络展示;运用DAVID数据库对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;Autodock-Tools、Vina对当归贝母苦参丸加味活性成分和关键靶点蛋白进行分子对接;通过Western Blot法验证活性成分与关键靶蛋白的相互作用。结果:筛选出当归贝母苦参丸加味活性成分67个,包括槲皮素、β-谷甾醇、天竺葵素、等重要成分,对应靶点411个,疾病靶点806个,药物与疾病的共有靶点155个;筛选出的核心靶点包括核转录因子κB(NF-κB)、白细胞介素-1β(IL-1β)、丝裂原活化蛋白激酶8(MAPK8)、MAPK14、IL-6、肿瘤坏死因子(TNF)等39个关键蛋白;GO富集分析得到凋亡过程的负调控、一氧化氮生物合成过程的正调控、MAP激酶活性的正调控、MAPK级联、核内NF-κB输入等369个生物过程,胞浆、细胞质、线粒体、蛋白质复合物等30个细胞组分,蛋白质结合、酶结合、一氧化氮合酶调节活性、MAP激酶活性、NF-κB结合等57个分子功能;KEGG富集分析得到TNF信号通路、PI3K-AKT信号通路、MAPK信号通路、雌激素信号通路、P53信号通路、NF-κB信号通路、等93条;分子对接显示β-谷甾醇与丝裂原活化蛋白Objective:To explore the mechanism of modified Danggui Beimu Kushen Pills(当归贝母苦参丸,MAFSPs)in the treatment of chronic prostatitis(CP)based on network pharmacology and molecular docking method.Methods:The active components of MAFSPs were obtained through Traditional Chinese Medicines Systems Pharmacology(TCMSP),Traditional Chinese Medicine Integrative Database(TCMID),and literature mining.Swiss Target Prediction Database was used to predict the targets of active components,and the existing targets of TCMSP Database were supplemented.The Online Mendelian Human Genetics Database(OMIM),GeneCards Database,and National Biotechnology Information Center(NCBI)Database were used to collect CP-related targets.The Chinese medicine-active component-target network diagram was constructed by using Cytoscape software.The STRING Database was used for bioinformatics analysis,and the target protein-protein interaction(PPI)network diagram was constructed.The core targets were screened out by CytoNCA,and the visual network display was carried out by Cytoscape.David Database was used to perform the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of core targets.Autodock-Tools and Vina were used to carry out molecular docking of MAFSP active components and key target proteins.The interaction between active components and key target proteins was verified by Western blot.Results:Sixty-seven active components of MAFSPs were screened out,including quercetin,β-sitosterol,geranium,and other important components.A total of 411 component targets,806 disease targets,and 155 common targets of drugs and diseases were obtained.The screened core targets included nuclear transcription factorsκB(NF-κB),interleukin-1β(IL-1β),mitogen-activated protein kinase 8(MAPK8),mitogen-activated protein kinase 14(MAPK14),interleukin-6(IL-6),tumor necrosis factor(TNF),and other 39 key proteins.GO enrichment analysis showed 369 biological processes such as negative regula

关 键 词：当归贝母苦参丸加味 慢性前列腺炎 网络药理学 作用机制 实验验证 

分 类 号：R285.5[医药卫生—中药学]