基于网络药理学探讨甘松-延胡索组方治疗房颤的作用机制

毛婷; 张京春; 刘蓓; 张珊; 艾玉珍

doi:10.13422/j.cnki.syfjx.20201203

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基于网络药理学探讨甘松-延胡索组方治疗房颤的作用机制

数据挖掘 | 更新时间：2020-08-11

- 基于网络药理学探讨甘松-延胡索组方治疗房颤的作用机制
- Mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma on Atrial Fibrillation Based on Network Pharmacology
- 中国实验方剂学杂志 2020年26卷第13期页码：190-198
- 作者机构：
  
  中国中医科学院西苑医院，心血管病研究所，北京 100091
- 作者简介：
  
  毛婷，在读博士，从事中医药防治心血管病研究，E-mail： maoting2017@163.com
  张京春，博士，主任医师，博士生导师，从事中医药防治心血管病研究，E-mail： zhangjingchun276@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81573817;81373825)
- DOI：10.13422/j.cnki.syfjx.20201203
  中图分类号： R2-0;R22;R285.5;R284
- 网络出版日期：2020-03-14，
  
  纸质出版日期：2020-07-05
- 稿件说明：
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毛婷,张京春,刘蓓等.基于网络药理学探讨甘松-延胡索组方治疗房颤的作用机制[J].中国实验方剂学杂志,2020,26(13):190-198.

MAO Ting,ZHANG Jing-chun,LIU Bei,et al.Mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma on Atrial Fibrillation Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):190-198.
毛婷,张京春,刘蓓等.基于网络药理学探讨甘松-延胡索组方治疗房颤的作用机制[J].中国实验方剂学杂志,2020,26(13):190-198. DOI： 10.13422/j.cnki.syfjx.20201203.

MAO Ting,ZHANG Jing-chun,LIU Bei,et al.Mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma on Atrial Fibrillation Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):190-198. DOI： 10.13422/j.cnki.syfjx.20201203.

摘要

目的

通过网络药理学预测甘松-延胡索组方治疗房颤的作用靶点及信号通路，进一步探讨潜在作用机制。

方法

采用中药系统药理学分析平台（TCMSP）筛选甘松-延胡索组方的活性成分并预测其作用靶点，构建活性成分-预测靶点网络。通过人类孟德尔遗传综合数据库（OMIM），治疗靶点数据库（TTD），基因组注释数据库（Genecards）检索房颤的潜在靶点，采用蛋白质相互作用网络数据库（STRING 11.0）获取房颤靶点蛋白相互作用的网络，通过Cytoscape 3.7.1软件对数据进行可视化分析，构建房颤靶点的蛋白互作网络。将甘松-延胡索组方的预测靶点映射至房颤靶点集合上，其交集靶点即为甘松-延胡索组方治疗房颤的潜在靶点。然后运用功能注释生物信息学分析平台（DAVID）数据库对甘松-延胡索组方治疗房颤的潜在靶点进行生物功能及信号通路富集分析。再通过Cytoscape 3.7.1软件构建甘松-延胡索组方治疗房颤的活性成分-潜在靶点-信号通路网络。

结果

筛选出51个甘松-延胡索组方的活性成分，预测出甘松-延胡索组方治疗房颤的潜在靶点18个，主要通过白细胞介素-6（IL-6），钠通道蛋白亚型5

（SCN5A），肿瘤坏死因子（TNF），内皮源性一氧化氮合酶（NOS3），电压依赖性钾通道亚型H2（KCNH2），胶原

1（I）链（COL1A1），维甲酸受体RXR-

（RXRA），组织因子（F3），

1B肾上腺素能受体（ADRA1B）等靶蛋白，以及环磷酸酸鸟苷（cGMP）/蛋白激酶G（PKG）信号通路，磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）信号通路，癌症中的转录失调，钙信号通路，心肌细胞中的肾上腺素信号等信号通路发挥治疗房颤的作用。

结论

甘松-延胡索组方是基于多成分、多靶点、多通路治疗房颤，为后续开展实验研究以进一步阐释其作用机制提供了科学依据。

Abstract

Objective

To investigate the mechanism of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation by predicting targets and signaling pathways based on network pharmacology.

Method

The traditional Chinese medicine system platform (TCMSP) database was used to screen out active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma

predict targets

and construct the active component-predicted target network.Through the Online Mendelian Inheritance in Man (OMIM)

Therapeutic Target Database (TTD)

and Genecards databases

potential target information of atrial fibrillation was retrieved.STRING 11.0 database was used to obtain the protein-protein interaction data of relevant targets

and the results were visualized by Cytoscape 3.7.1 software to construct protein-protein interaction network relating to atrial fibrillation.The predicted targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were mapped to the potential targets of atrial fibrillation.The intersection targets were the potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma.Then

Visualization and Integrated Discovery (DAVID)

a database for annotation

was used to analyze biological functions and pathways of the potential targets of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in the treatment of atrial fibrillation.Finally

Cytoscape3.7.1 software was utilized to construct active component-potential target-signal pathway network of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma in treatment of atrial fibrillation.

Result

Totally 51 active components of Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were screened out

and 18 potential targets for the treatment of atrial fibrillation with Nardostachyos Radix et Rhizoma and Corydalis Rhizoma were predicted.The effect was mainly correlated with the regulation of interleukin-6 (IL-6)

sodium channel protein type 5 subunit alpha (SCN5A)

tumor necrosis factor (TNF)

nitric-oxide synthase

endothelial (NOS3)

potassium voltage-gated channel subfamily hmember 2 (KCNH2)

collagen alpha-1(I) chain (COL1A1)

retinoic acid receptor RXR-alpha (RXRA)

tissue factor (F3)

alpha-1B adrenergic receptor (ADRA1B) and other target proteins

cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase G (PKG) signaling pathway

phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt) signaling pathway

transcriptional disorders in cancer

calcium signaling pathways

and adrenergic signals in cardiomyocytes.

Conclusion

Nardostachyos Radix et Rhizoma and Corydalis Rhizoma treat atrial fibrillation based on multiple components

multiple targets and multiple channels

and provide a scientific basis for subsequent experimental studies for further explainning its mechanism of action.

关键词

Keywords

references

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