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中华重症医学电子杂志 ›› 2022, Vol. 08 ›› Issue (04) : 353 -359. doi: 10.3877/cma.j.issn.2096-1537.2022.04.013

重症医学研究

基于数据挖掘和网络拓扑学对藏药红景天调控脑微循环作用靶点和信号通路的筛选
马四清1, 陈强1,(), 徐颖1, 闫秀娟2, 刘娟丽1   
  1. 1. 810007 西宁,青海省人民医院重症医学科
    2. 810007 西宁,青海省第五人民医院神经内科
  • 收稿日期:2022-11-07 出版日期:2022-11-28
  • 通信作者: 陈强
  • 基金资助:
    青海省科技计划项目(2020-ZJ-754)

Screening target and signal pathway regulating cerebral microcirculation of the Tibetan medicine Rhodiola based on data mining and network topology

Siqing Ma1, Qiang Chen1,(), Ying Xu1, Xiujuan Yan2, Juanli Liu1   

  1. 1. Department of Critical Care Medicine, Qinghai Provincial People's Hospital, Xining 810007, China
    2. Department of Neurology, the Fifth People's Hospital of Qinghai Province, Xining 810007, China
  • Received:2022-11-07 Published:2022-11-28
  • Corresponding author: Qiang Chen
引用本文:

马四清, 陈强, 徐颖, 闫秀娟, 刘娟丽. 基于数据挖掘和网络拓扑学对藏药红景天调控脑微循环作用靶点和信号通路的筛选[J/OL]. 中华重症医学电子杂志, 2022, 08(04): 353-359.

Siqing Ma, Qiang Chen, Ying Xu, Xiujuan Yan, Juanli Liu. Screening target and signal pathway regulating cerebral microcirculation of the Tibetan medicine Rhodiola based on data mining and network topology[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2022, 08(04): 353-359.

目的

基于化学相似性靶点预测与网络拓扑学分析方法,对藏药红景天改善脑微循环潜在作用靶点进行虚拟筛选。

方法

通过化学成分数据库及相关文献信息提取收集红景天化学成分,利用药代动力学参数(如吸收、分布、代谢、排泄,即ADME)筛选出活性成分;利用swiss在线靶点预测平台采用化学相似性方法预测红景天活性成分的潜在靶点;通过GeneCards数据库获取脑微循环相关靶点,并获取红景天活性成分与脑微循环共有靶点;利用STRING数据库获取共有靶点蛋白间相互作用关系;利用Cytoscape软件构建蛋白质间相互作用(PPI)网络模型,基于网络拓扑学算法获取核心靶点(core target);最后,对共有靶点进行KEGG分析,明确藏药红景天改善脑微循环的主要信号通路。

结果

从藏药红景天中筛选出76个活性成分和660个靶点,获取脑微循环相关靶点526个,交集靶点141个,核心靶点AKT1、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)、甘油醛-3-磷酸脱氢酶(GAPDH)、丝裂原活化蛋白激酶3(MAPK3)、表皮生长因子受体(EGFR)、非受体酪氨酸激酶(SRC)、胱天蛋白酶(Casp 3),反向查找核心靶点相关成分,获取25个关键活性成分。《京都议定书》的基因与基因组百科全书(KEGG)通路富集分析得到150条通路(P<0.01),其中最主要的信号通路包括:缺氧诱导因子(HIF)-1信号通路、Rap1信号通路、黏着斑、松弛素信号通路、Ras信号通路、磷酸肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路、TNF信号通路、ErbB信号通路

结论

藏药红景天可通过多成分、多靶点、多通路协同发挥改善脑微循环作用,该研究初步筛选出了藏药红景天调控脑微循环潜在作用靶点及作用的信号通路,为进一步拓展应用藏药红景天的脑保护(药理作用)提供了较为丰富的理论依据。

Objective

To virtually screen out the potential targets improving brain microcirculation of the Tibetan medicine Rhodiola, based on chemical similarity target prediction and network topology analysis methods.

Methods

The active ingredients of Rhodiola based on chemical composition database and related literatures, were selected by pharmacokinetic parameters (ADME). The swiss online target prediction platform was used to predict potential targets of active components of Rhodioal sachalinensis by chemical similarity method. Obtaining brain microcirculation-related targets through the GeneCards database, and obtaining the Rhodiola active components and brain microcirculation common target. Common target proteins were linked to the STRING database. Construction of a protein-protein interaction (PPI) network model using Cytoscape software. Obtaining core targets (core target) based on network topology algorithm. For KEGG analysis of the common targets, to clarify which signaling pathways are potential targets of Rhodiola to improve brain microcirculation.

Results

Seventy-six active components and 660 targets were selected from Tibetan medicine Rhodiola to obtain 526 brain microcirculation related targets, 141 intersection targets, core targets AKT1, TNF, VEGFA, GAPDH, MAPK3, EGFR, SRC, Casp 3, and reverse find core target related components to obtain 25 key active components. The KEGG analysis selected 150 pathways (P<0.01), and the main signaling pathways include: HIF-1 signaling pathway, Rap1 signaling pathway, focal adhesion plaque, relaxin signaling pathway, Ras signaling pathway, and PI3K-Akt signaling pathway, TNF signaling pathway, and ErbB signaling pathway.

Conclusion

Tibetan medicine Rhodiola can improve the role of brain microcirculation through multi-component, multi-target and multi-pathway coordination. This study has preliminarily screened out the potential targets and signal pathway of regulating cerebral microcirculation, which provides a rich theoretical basis for further expanding the application of Tibetan medicine Rhodiola brain protection and pharmacology.

图1 红景天与脑微循环相关靶点韦恩图
图2 红景天与脑微循环共同靶点PPI网络。绿色节点代表红景天调控脑微循环的核心靶点,蓝色节点代表其他潜在靶点,线条代表节点间相互作用注:PPI为蛋白质间相互作用
图3 红景天改善脑微循环的核心靶点相互作用网络。绿色节点代表核心靶点蛋白,线条代表节点间相互作用,线条越粗,表示两个靶点蛋白间相互作用越强注:VEGFA为血管内皮生长因子A;GAPDH为甘油醛-3-磷酸脱氢酶;MAPK3为丝裂原活化蛋白激酶3;EGFR为表皮生长因子受体;SRC为非受体酪氨酸激酶;Casp 3为胱天蛋白酶;TNF为肿瘤坏死因子
表1 药材红景天关键活性成分与核心靶点的关系
编号 药材 关键活性成分 核心靶点 编号 药材 关键活性成分 核心靶点
1 红景天 3-Octanol EGFR 21 红景天 quercetin AKT1
2 红景天 Formic Acid Hexyl Ester EGFR 22 红景天 5-O-Caffeoylshikimic acid Casp 3
3 红景天 Umbelliferone EGFR 23 红景天 Ferulic acid EGFR
4 红景天 Umbelliferone AKT1 24 红景天 Rhodioloside E Casp 3
5 红景天 Caffeic Acid EGFR 25 红景天 Creoside Ⅳ VEGFA
6 红景天 kaempferol EGFR 26 红景天 Creoside Ⅲ TNF
7 红景天 kaempferol SRC 27 红景天 Creoside Ⅲ EGFR
8 红景天 kaempferol AKT1 28 红景天 Isolariciresinol MAPK3
9 红景天 Ethyl Gallate SRC 29 红景天 2-(4-Hydroxyphenyl)ethyl 3,4,5-trihydroxybenzoate SRC
10 红景天 crenulatin VEGFA 30 红景天 Sachaloside Ⅱ VEGFA
11 红景天 crenulatin GAPDH 31 红景天 Sachaloside Ⅱ EGFR
12 红景天 crenulatin EGFR 32 红景天 Eriodictyol SRC
13 红景天 5,4′-dihydroxy-7,3′-dimethoxyflavone EGFR 33 红景天 Eriodictyol AKT1
14 红景天 5,4′-dihydroxy-7,3′-dimethoxyflavone AKT1 34 红景天 Rhodiooctanoside VEGFA
15 红景天 5,4′-dihydroxy-7,3′-dimethoxyflavone SRC 35 红景天 Creoside Ⅴ VEGFA
16 红景天 tricin EGFR 36 红景天 oxiranemethanol,3-methyl-3-(4-methyl-3-pentenyl)- EGFR
17 红景天 tricin SRC 37 红景天 2-hydroxy-1,1,10-trimethyl-6,9-epidioxydecalin EGFR
18 红景天 tricin AKT1 38 红景天 geranyl acetate EGFR
19 红景天 quercetin EGFR 39 红景天 farnesal EGFR
20 红景天 quercetin SRC
图4 红景天改善脑微循环潜在靶点KEGG通路富集分析
表2 红景天改善脑微循环潜在靶点KEGG富集分析结果
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