基于网络药理学的丹参治疗哮喘作用机制初探  

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma Against Asthma Based on Network Pharmacology

作　　者：李凡 刘久石 李斌 齐耀东[1] 张本刚[1] 刘海涛[1] 肖培根[1] LI Fan;LIU Jiu-shi;LI Bin;QI Yao-dong;ZHANG Ben-gang;LIU Hai-tao;XIAO Pei-gen(Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,Ministry of Education,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所中草药物质基础与资源利用教育部重点实验室,北京100193

出　　处：《中国现代中药》2021年第10期1727-1736,共10页Modern Chinese Medicine

基　　金：中国医学科学院医学与健康科技创新工程项目(2020-I2M-2-011)。

摘　　要：目的:运用网络药理学方法探讨丹参治疗哮喘的作用靶点及通路。方法:通过中药系统药理学数据库与分析平台(TCMSP)获取丹参活性成分及潜在靶点;应用OMIM、GeneCards、TTD、DrugBank和DisGeNET数据库收集哮喘靶点,利用R语言获得丹参治疗哮喘的作用靶点,依据STRING 11.0数据库获取蛋白质-蛋白质相互作用(PPI)网络;在Metascape平台进行京都基因与基因组百科全书(KEGG)和基因本体(GO)分析,运用Cytoscape 3.5.1软件构建丹参治疗哮喘的成分-靶点-通路网络,并筛选核心靶点,采用MOE 2019软件对重要化合物进行分子对接验证。结果:筛选得到丹参治疗哮喘的59个化学成分、108个靶点及20条关键通路。其中,隐丹参酮主要通过肿瘤坏死因子(TNF)、Toll样受体4(TLR4)等蛋白抑制核转录因子-κB(NF-κB)通路,减轻哮喘气道炎症;丹参酮Ⅱ_(A)主要通过核转录因子-κB抑制剂α(NFKBIA)等减弱TNF-α和NF-κB表达,抑制NF-κB通路,减轻炎症损伤;木犀草素主要通过蛋白激酶B1(Akt1)、白细胞介素-6(IL-6)和信号传导与转录激活因子3(STAT3)等介导磷脂酰肌醇3-激酶(PI3K)-Akt和Janus激酶-信号转导子与转录激活因子(JAK-STAT)通路,通过缓解气道炎症、改善气道重塑和免疫调节治疗哮喘。分子对接显示,三者与疾病靶点生物亲和力高。结论:丹参可以通过多成分、多靶点、多途径发挥治疗哮喘的作用。Objective:To investigate the potential mechanism of Salviae Miltiorrhizae Radix et Rhizoma in the treatment of asthma based on network pharmacology and molecular docking.Methods:The active components and corresponding target proteins of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of asthma from GeneCards,Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and DisGeNET.R language was used to yield the common targets of the medicinal and the disease,and STRING 11.0 to construct the protein-protein interaction(PPI)network.Gene Ontology(GO)term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of common targets were performed on Metascape platform.Then the Salviae Miltiorrhizae Radix et Rhizoma component-target-pathway network was constructed with Cytoscape 3.5.1 and the core targets were screened.MOE 2019 was employed for molecular docking of the 10 major targets and the main active components.Results:A total of 59 active components of Salviae Miltiorrhizae Radix et Rhizoma,108 common targets of the medicinal and the disease,and 20 key pathways were screened out.Among them,cryptotanshinone may inhibit nuclear factor-κB(NF-κB)pathway through tumor necrosis factor(TNF)and toll-like receptor 4(TLR4)and tanshinone Ⅱ_(A) mainly suppressed the NF-κB pathway through weakened nuclear factor-κB-inhibitor alpha(NFKBIA)expression.Luteolin can mediate phosphatidylinositol 3 kinase-protein kinase B(PI3K-Akt)and janus kinase/signal transducers and activators of transcription(JAK-STAT)pathways through protein kinase B(Akt1),interleukin-6(IL-6),and signal transducer and activators of transcription 3(STAT3),and treat asthma by relieving airway inflammation,improving airway remodeling,and immune regulation.Molecular docking shows that the three compounds have high biological affinity with disease targets.Conclusion:This study reflect

关 键 词：丹参 哮喘 网络药理学 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]