网络药理学常见不同富集方法比较研究#br#
——以当归补血汤治疗贫血为例

中国医药导刊 ›› 2022, Vol. 24 ›› Issue (4): 398-405.

网络药理学常见不同富集方法比较研究#br# ——以当归补血汤治疗贫血为例

王颖1，台安宁1，吴国泰1，2，邵晶1，2，王瑞琼1，2，段海婧1，2，任远1，2*，杜丽东1，2*

1.甘肃中医药大学，甘肃兰州 730000； 2.甘肃省中药药理与毒理学重点实验室，甘肃兰州 730000

收稿日期:2022-01-25 修回日期:2022-04-25 出版日期:2022-04-28 发布日期:2022-04-28
基金资助:
甘肃省中医药科研立项课题资助项目（项目编号：GZK-2019-23；项目名称：基于数据挖掘和网络药理学探索乌梅丸治疗溃疡性结肠炎的有效成分及作用机制）；甘肃省中医药研究中心开放课题（项目编号：ZYZX-2020-20；项目名称：溃疡性结肠炎大鼠肺肠同病的屏障共损伤及乌梅丸的干预作用研究）；2019 年陇原青年创新创业人才( 团队) 项目(项目编号：甘组通字〔2019〕37 号－41；项目名称：道地药材当归的现代产业技术体系建设) ；2019 年甘肃省重点人才项目( 项目编号：甘组通字〔2019〕37号－07；项目名称：当归油研究及产业化开发)

Comparative Study on Different Enrichment Methods in Network Pharmacology——Taking the Treatment of Anemia with Danggui Buxue Decoction as An Example

杜丽东 bella杜丽东

1.Gansu University of Traditional Chinese Medicine，Gansu Lanzhou 730000，China; 2.Key Laboratory of Traditional Chinese Medicine Pharmacology and Toxicology in Gansu Province，Gansu Lanzhou 730000，China

Received:2022-01-25 Revised:2022-04-25 Online:2022-04-28 Published:2022-04-28

摘要/Abstract

摘要： 目的：以当归补血汤治疗贫血为例比较常见网络药理学不同富集方法的差异，并对当归补血汤的活性成分和核心靶点进行分子对接，为后续网络药理学研究提供参考。方法：从TCMSP数据库、UniProt数据库、Gene Cards数据库获取当归补血汤活性成分、作用靶点及贫血相关靶点，用在线Venny 2.1.0平台对活性成分作用靶点和贫血靶点取交集，用Cytoscape 3.7.1绘制药物-活性成分-靶点-疾病网络。交集靶点导入STRING蛋白互作数据库构建PPI网络，取DC值的2倍中位数得到核心靶点。使用 AutoDock软件对活性成分和核心靶点进行分子对接、验证成分和靶点的结合性。用Metascape数据库、DAVID数据库、Cytoscape软件的GlueGO插件及R语言的“clusterProfiler”程序包对核心靶点进行基因本体论（gene ontology，GO）富集分析和京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）通路分析，取KEGG通路分析结果前20条信号通路进行比较。结果：当归补血汤活性成分共22个，对应靶点212个，与疾病靶点相交共167个；“DC≥53”的核心靶点43个，PPI网络中排名靠前的靶点AKT1、VEGFA、TP53、IL-6、CASP3、TP53；活性成分MOL000211（白桦脂酸）与各靶点的结合活性均为最优；4个数据库富集的前20条通路中，9条通路是4种方法共有通路，6条通路是3种方法共有通路，8条通路是2种方法共有通路，其余10条通路均为单一方法富集得到的通路。结论：经典方剂当归补血汤通过多成分、多靶点、多通路治疗贫血病症；4种不同富集方法得到的信号通路有重合也存在差异。为提高网络药理学在后续实验研究的指导性，建议多种富集方法联用取交集。

关键词: font-size:medium, ">网络药理学；当归补血汤；贫血；KEGG通路分析, GO功能富集分析

Abstract: Objective：Taking the treatment of anemia by danggui buxue decoction as an example to compare the difference of different network pharmacology enrichment methods， and the active components and core targets of danggui buxue decoction were identified by molecular docking， to provide a reference for the follow-up study of network pharmacology.Methods:The TCMSP database， UniProt datebase， Gene Cards database were used to screen the chemical components， corresponding targets of danggui buxue decoction and the targets related to anemia. The online Venny 2.1 platform was used to intersection the target of active ingredients with the target of anemia， and cytoscape 3.7.1 was used to map the drug-active compound-target-disease network.The intersection targets were imported into STRING protein interaction database to construct PPI network， and the core targets were obtained by taking 2 times median of DC value.The molecular docking of potential active compounds and core targets were achieved by autodock. Metascape database， DAVID database and GlueGO plug-in of Cytoscape software and "clusterProfiler" package of R language were used for the GO function and KEGG pathway enrichment analysis of the targets. The top 20 signal pathways with enrichment results of KEGG pathway were compared.Results:Danggui buxue decoction obtained 22 active components and 212 corresponding targets， 167 common targets were obtained related with anemia， among which 43 proteins exceeded "DC≥53"， and the top targets in PPI network were AKT1， VEGFA， TP53， IL-6， CASP3 and TP53. The active ingredient MOL000211(betulinic acid) had the best binding activity with each target. Among the top 20 pathways enriched by 4 databases， 9 pathways were shared by 4 methods， 6 pathways were shared by 3 methods， 8 pathways were shared by 2 methods， and the remaining 10 pathways were all obtained by single method enrichment.Conclusion:The classic prescription of danggui buxue decoction may treat anemia through multi-component， multi-target and multi-pathway. The signal pathways obtained by the 4 different enrichment methods overlapped and differed. In order to improve the target of network pharmacology in subsequent experimental studies， it is suggested to combine multiple enrichment methods to take intersection.

Key words: Network pharmacology, Danggui buxue decoction, Anemia, KEGG pathway analysis, GO funciton enrichment analysis

中图分类号:

王颖, 台安宁, 吴国泰, 邵晶, 王瑞琼, 段海婧, 任远, 杜丽东, . 网络药理学常见不同富集方法比较研究#br# ——以当归补血汤治疗贫血为例[J]. 中国医药导刊, 2022, 24(4): 398-405.

WANG Ying, TAI Anning, WU Guotai, SHAO Jing, WANG Ruiqiong, DUAN Haijing, REN Yuan, DU Lidong, . Comparative Study on Different Enrichment Methods in Network Pharmacology——Taking the Treatment of Anemia with Danggui Buxue Decoction as An Example[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(4): 398-405.

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