Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology

Hai ZHOU; Xiao-ling WU; Ming-xin LIN; Zhang-zhi ZHU

doi:10.13422/j.cnki.syfjx.20191528

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Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology

Data Mining | 更新时间：2021-02-09

- Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 23, Pages: 176-186(2019)
- 作者机构：
  
  1.广州中医药大学　第一临床医学院，广州　 510405；
  2.深圳市宝安区中医院，广东　深圳　 518000；
  3.中国中医科学院　中医基础理论研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191528
  CLC： R22; R242; R2-031; R285.5
- Received：17 January 2019，
  
  Published Online：19 April 2019，
  
  Published：05 December 2019
- 稿件说明：
移动端阅览
Hai ZHOU, Xiao-ling WU, Ming-xin LIN, et al. Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 176-186.
DOI：

Hai ZHOU, Xiao-ling WU, Ming-xin LIN, et al. Mechanism of Modified Taohe Chengqitang in Treating Diabetic Nephropathy Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(23): 176-186. DOI： 10.13422/j.cnki.syfjx.20191528.

摘要

目的：

运用计算机网络药理学技术预测加味桃核承气汤治疗糖尿病肾病的作用靶点和信号通路，进一步分析其防治糖尿病肾病的基础和作用机制。

方法：

运用中药系统药理学成分分析平台Bioinformatics Analysis Toolfor Molecular mechANism of TCM(BATMAN-TCM)数据库获取加味桃核承气汤的有效成分及作用靶标基因，从Comparative Toxicogenomics Database(CTD)数据库收集糖尿病肾病的靶标基因，将两者取交集后得到疾病-药物蛋白靶基因，运用STRING构建蛋白质间相互作用网络，并通过Cytoscape软件将结果进行网络可视化展示，通过网络结构和节点间加权重联系的计算分析算法筛选出作用的关键基因。借助DAVID在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析，并采用Cytoscape 软件BiNGO插件和ClueGO插件对靶点进行基因功能(GO)分析和基于KEGG通路富集分析的可视化展示。最后利用CTD数据库并结合文献学习，获取关键基因于糖尿病肾病的疾病治疗作用。

结果：

加味桃核承气汤的621个化合物中有581个靶点与糖尿病肾病相互关联。其中NOS3，OAT，NT5C2，ACACB，AGXT，PDE3B等关键基因主要通过调控神经组织的传递、胆碱能突触通路、钙离子通道、代谢通路、嘌呤代谢通路、血管紧张素-神经突触通路、环磷酸腺苷信号通路以及环磷酸鸟苷/环磷酸鸟苷酸依赖的蛋白激酶(cGMP/PKG)信号通路等路径，在质膜、突触后膜、线粒体等分子反应中发挥作用。

结论：

网络药理学方法科学预测加味桃核承气汤防治糖尿病肾病的关键靶标及其参与的相关通路，提示该方剂对糖尿病肾病的防治作用为多靶点、多通路、多选择的复杂机制，并且多与抗炎、氧化磷酸化及介导嘌呤代谢等机制相关。

Abstract

Objective:

To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic nephropathy by means of network pharmacology.

Method:

Target genes of modified Taohe Chengqitang were obtained from BAT-MAN database

while target genes of diabetic nephropathy were obtained from CTD database. The target genes of disease-drug protein were obtained by crossing two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The key genes were screened out through the computational analysis algorithm of network structure and weighted relatedness between nodes. With DAVID online tools

gene ontology (GO) analysis of Disease-Drug Intersection Target Genes and enrichment analysis of kyoto encyclopedia of genes and genomes(KEGG) pathway were conducted. Finally

CTD database and literature study were used to obtain the key genes in the treatment of diabetic nephropathy.

Result:

Among 621 compounds in modified Taohe Chengqitang

581 of them were related to diabetic nephropathy. NOS3

OAT

NT5C2

ACACB

AGXT

PDE3B and other key genes mainly regulated nerve tissue transmission

cholinergic synaptic pathway

calcium channel

metabolic pathway

purine metabolic pathway

angiotensin-neurosynaptic pathway

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

with effect in molecular reactions

such as plasma membrane

postsynaptic membrane and mitochondria.

Conclusion:

The network pharmacology predicts the key targets of modified Taohe Chengqitang in the prevention and treatment of diabetic nephropathy and the related pathways involved

suggesting a multi-target

multi-channel and multi-choice complex mechanism

and which is mostly related to anti-inflammation

oxidative phosphorylation and purine metabolism.

关键词

Keywords

references

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