Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology

Yi-ming BI; Bei YIN; Ya-qing XIA; Guan-jie FAN

doi:10.13422/j.cnki.syfjx.20202060

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Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology

Data Mining | 更新时间：2020-12-10

- Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 24, Pages: 169-177(2020)
- 作者机构：
  
  1.广州中医药大学第二临床医学院，广州 510006
  2.广州中医药大学第二附属医院，广州 510120
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202060
  CLC： R285;R289;R22;R2-031
- Received：02 January 2020，
  
  Published Online：23 July 2020，
  
  Published：20 December 2020
- 稿件说明：
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毕艺鸣,殷贝,夏亚情等.基于网络药理学探讨四逆散治疗2型糖尿病的作用机制[J].中国实验方剂学杂志,2020,26(24):169-177.

BI Yi-ming,YIN Bei,XIA Ya-qing,et al.Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):169-177.
毕艺鸣,殷贝,夏亚情等.基于网络药理学探讨四逆散治疗2型糖尿病的作用机制[J].中国实验方剂学杂志,2020,26(24):169-177. DOI： 10.13422/j.cnki.syfjx.20202060.

BI Yi-ming,YIN Bei,XIA Ya-qing,et al.Mechanism of Sinisan in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):169-177. DOI： 10.13422/j.cnki.syfjx.20202060.

摘要

目的

运用网络药理学方法研究四逆散治疗2型糖尿病（T2DM）的作用机制，旨在为其基础研究及临床应用提供依据。

方法

通过多个数据库检索并筛选四逆散中不同药物的活性成分及其与T2DM的交集靶点，通过Cytoscape分别构建药物、靶点、疾病靶点网络图；利用STRING数据库构建交集靶点的PPI网络，利用CytoNCA进行网络拓扑分析，利用Cluster Marker进行网络模块化分析，再通过ClueGO进行基因功能（GO），京都基因和基因组合百科全书（KEGG）富集分析。

结果

四逆散中筛选得到137个活性成分，涉及T2DM靶点110个；CytoNCA分析筛选出12个关键靶点。Cluster Marker分析提示，交集靶点分别涉及4个模块，GO分析结果显示：模块一主要涉及急性炎症反应、乙酰胆碱受体信号通路等生物学过程；模块二主要涉及类固醇刺激的反应，对外源性刺激的反应等；而模块三主要参与细胞对各种营养物质的代谢反应以及对缺氧的调控反应等。KEGG分析主要与晚期糖基化终末产物及其受体通路、凋亡通路、炎症通路、细胞周期以及各种代谢通路高度相关。

结论

四逆散治疗T2DM可能是其综合调控炎症、细胞凋亡、物质代谢等的结果。该研究不仅揭示了四逆散治疗2型糖尿病的潜在机制，还揭示了四逆散与糖尿病血管并发症、糖尿病认知障碍及恶性肿瘤的关系，为四逆散的基础研究提供方向。

Abstract

Objective

To investigate the mechanism of Sinisan in treating type 2 diabetes mellitus（T2DM） based on network pharmacology.

Method

Based on electronic databases， active ingredients of Sinisan and target genes of ingredients as well as type 2 diabetes were screened out. Cytoscape software was applied to construct "herb-active ingredient-target-disease" interaction network diagram，respectively. The common genes of ingredients and disease were uploaded to the STRING database， and the protein interaction network map （PPI） was constructed. CytoNCA and Cluster Marker were used to analyze PPI，respectively. Finally，ClueGO was used to analyze gene ontology （GO） enrichment and Kyoto Encyclopedia of genes and genomes （KEGG） pathway enrichment.

Result

A total of 137 active components and 110 effective genes of Sinisan in the treatment of type 2 diabetes were screened out. Based on PPI analysis，these effective genes were divided into 4 different clusters， and 12 genes were considered as the most effective targets. GO enrichment analysis showed that cluster 1 mainly involved acute inflammatory response and acetylcholine receptor signaling pathway， cluster 2 mainly involved cellular response to steroid hormone stimulu and xenobiotic stimulus，and cluster 3 was mainly engaged in the metabolism process of protein，fatty and glucose and the response to hypoxia. KEGG analysis was highly correlated with advanced glycation end products-receptor for AGE （AGE-RAGE） pathway，apoptosis pathway，inflammatory pathway，cell cycles and various metabolic pathways.

Conclusion

Sinisan has a regulatory effect in pathogenesis and prognosis of T2DM，such as inflammation，cell apoptosis and nutrition metabolism. Moreover，its potential mechanisms on diabetic angiopathies，diabetic cognitive impairment and cancers were reveal，so as to define a direction for the fundamental research of Sinisan.

关键词

Keywords

references

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