Research on saponin active compounds of Tuchao Baibiandouren for the treatment of type-2 diabetes based on UHPLC-Q-Exactive Orbitrap MS and network pharmacology  

基于UHPLC-Q-Exactive Orbitrap MS及网络药理学研究土炒白扁豆仁皂苷活性成分治疗2型糖尿病的作用

作　　者：FANG Liangzi ZHENG Qinfang HAN Jun 方良子;郑钦方;韩君(湖南中医药大学科技创新中心,湖南长沙410208;湖南医药学院侗医药研究湖南省重点实验室,湖南怀化418000;北京康仁堂药业有限公司中药配方颗粒关键技术国家地方联合工程研究中心,北京101301)

机构地区：[1]Science and Technology Innovation Center,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China [2]Key Laboratory of Dong Medical Research of Hunan Province,Hunan University of Medicine,Huaihua,Hunan 418000,China [3]National and Local Joint Engineering Research Center for Key Technology of Chinese Medicinal Composition Granules,Beijing Tcmages Pharmaceutical Co.,Ltd.,Beijing 101301,China

出　　处：《Digital Chinese Medicine》2021年第1期19-31,共13页数字中医药（英文）

基　　金：We thank for the funding support from the Program of Survey of Chinese Medicines of China(No.[2017]66).

摘　　要：Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren(Lablab Semen Album fried with earth,TCBBDR)in treating type 2 diabetes(T2DM)using UHPLC-Q-Exactive Orbitrap MS and network pharmacology.Methods UHPLC-Q-Exactive Orbitrap MS was used for a qualitative analysis of saponin compounds in TCBBDR.PharmMapper and CTD were used to screen drug active compounds and disease targets,and an active compound-target network was constructed via Cytoscape 3.8.0.Molecular docking was applied with the drug active compounds and key targets using AutoDock Vina 1.1.2,and a trajectory for the molecular dynamics simulation was completed by GROMACS 2019-3.Results Sixteen saponin compounds were identified from TCBBDR,along with 292 saponin compoud targets and 792 T2DM targets.Through Venn analysis of target saponin constituents and T2DM related targets,a total of 91 intersection targets were screened out in the treatment of T2DM with saponin.The mean values of degree,betweenness centrality and closeness centrality were taken as the thresholds to screen out 22 key genes,among which 4 key proteins namely MAPK1,IGF1 EGFR,PIK3R1 were selected in the top 10 key genes.On this basis,the saponin active constituent-target-signaling pathway network was established.The Gene Ontology(GO)enrichment analysis showed that the related biological modules included activity of steroid hormone receptor,steroid binding,and insulin receptor binding,etc.;the related signaling pathways were EGFR,PI3K-Akt and MAPK,etc.;regulating signaling pathways like MAPK could induce the proliferation,inhibition and apoptosis of pancreaticβcells,increase the quantity of pancreaticβcells,improve the functions of pancreaticβcells and stimulate the insulin secretion.Docking experiment analysis showed that all selected saponin compounds could enter the active sites of targets and form 3–14 hydrogen bonds with residues of the active sites.Moreover,van der Waals forces were present between chemical compounds and active sites.By 目的基于UHPLC-Q-Exactive Orbitrap MS及网络药理学探究土炒白扁豆仁皂苷活性成分治疗2型糖尿病(T2DM)的药理作用机制。方法采用UHPLC-Q-Exactive Orbitrap MS对土炒白扁豆仁皂苷化学成分进行定性分析,利用PharmMapper、CTD等数据库筛选化合物和疾病靶点,利用Cytoscape 3.8.0构建活性成分-靶点网络,利用AutoDock Vina 1.1.2对活性成分和关键靶点进行分子对接实验,分子动力学模拟的轨迹由GROMACS 2019-3完成。结果从土炒白扁豆仁中共鉴定了16个皂苷成分,筛选出皂苷成分靶点292个,T2DM靶点792个。将皂苷成分靶点与T2DM相关靶点经过Venn分析,得到皂苷治疗T2DM的交集靶点91个。以degree,betweenness centrality,closeness centrality的平均值作为阈值筛选出22个关键基因,在其中关联度前10个基因中选择了MAPK1,IGF1,EGFR和PIK3R14个基因建立皂苷活性成分-靶点-信号通路网络图。GO富集分析显示相关生物模块包括类固醇激素受体活性、类固醇结合、胰岛素受体结合等;信号通路显示相关通路包括EGFR信号通路、PI3K-Akt信号通路、MAPK信号通路等。经分子对接研究可知化合物均能进入目标靶点的活性位点,并与活性位点残基形成3−14个氢键,且化合物与活性位点之间普遍存在范德华力,结合对接结合能可知,各化合物与目标靶点具有较强的结合能。结论土炒白扁豆仁通过多组分、多靶点协同起到治疗糖尿病作用;它通过调节与EGFR相互作用的几种关键蛋白和一系列与疾病发展相关的信号通路来介导疾病炎症反应、信号传导等过程来治疗糖尿病。

关 键 词：UHPLC-Q-Exactive Orbitrap MS Network pharmacology Tuchao Baibiandouren(Lablab Semen Album fried with earth TCBBDR) Type-2 diabetes Molecular docking Molecular dynamics simulation 

分 类 号：R285[医药卫生—中药学]