Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics

Gong ZHANG; Ying YU; Hai-liang HUANG; Si-chao ZHANG

doi:10.13422/j.cnki.syfjx.20192438

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Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics

Data Mining | 更新时间：2021-02-09

- Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 24, Pages: 142-149(2019)
- 作者机构：
  
  山东中医药大学　中医学院，康复学院，济南　 250355
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192438
  CLC： R2-0; R285; R289
- Published：20 December 2019，
  
  Published Online：03 September 2019，
  
  Received：04 May 2019，
- 稿件说明：
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Gong ZHANG, Ying YU, Hai-liang HUANG, et al. Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(24):142-149(2019)
DOI：

Gong ZHANG, Ying YU, Hai-liang HUANG, et al. Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(24):142-149(2019) DOI： 10.13422/j.cnki.syfjx.20192438.

摘要

目的：

运用网络药理学与生物信息学方法挖掘四神丸治疗溃疡性结肠炎的作用靶点和相关信号通路，探究该方治疗溃疡性结肠炎的作用机制。

方法：

通过检索中医药百科全书数据库(ETCM)获取四神丸有效的活性成分及预测靶基因，从基因表达集(GEO)芯片数据库及基因疾病关联数据库(DisGeNET)，人类孟德尔遗传综合数据库(OMIM)，药物靶标数据库(DrugBank)，比较毒物基因组数据库(CTD)，遗传药理学与药物基因组学数据库(PharmGKB)疾病数据库收集溃疡性结肠炎的疾病靶基因，将两者取交集得到药物-疾病蛋白靶基因，并通过Cytoscape软件将结果进行网络化展示，通过网络拓扑算法筛选出作用的关键靶基因，运用基因本体富集分析软件工具包(GOEAST)与注释、可视化和集成发现数据库(DAVID)在线工具对关键靶基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析，结合相关文献分析四神丸防治溃疡性结肠炎的作用机制。

结果：

四神丸所含草药的活性成分182个，预测靶标611个；通过疾病数据库检索与溃疡性结肠炎发生发展相关的已知疾病靶标914个；四神丸主要作用于溃疡性结肠炎的类固醇激素介导信号通路、外源代谢过程，RNA聚合酶Ⅱ启动子转录的正调控、脂质代谢过程、细胞氧化剂解毒、信号转导等生物学功能，参与花生四烯酸、药物代谢-细胞色素P450，细胞色素P450对异种生物、化学致癌等关键信号通路。

结论：

四神丸治疗溃疡性结肠炎具有多靶点、多途径、多层次的特性，其所作用的多条信号通路均存在直接或间接关联性，参与脂质蛋白代谢、药物代谢及抗癌机制等方面，并通过对机体的消化系统、循环系统、免疫系统等多系统综合干预而发挥药效，因此与多因素所诱导的溃疡性结肠炎发病的综合效应机制相吻合。

Abstract

Objective:

To investigate the mechanism of Sishenwan in the treatment of Ulcerative Colitis and to explore the key targets and signal pathway on the treatment of Ulcerative Coltis based on network pharmacology and bioinformatics.

Method:

To obtain the active ingredients and predicted target genes of Sishenwan by searching the Encyclopedia of Traditional Chinese Medicine(ETCM) database

from the Gene Expression Omnibus (GEO) database and Database of Gene-disease Associations (DisGeNET)

Online Mendelian Inheritance in Man (OMIM)

Drug-targetDatabase (DrugBank)

The Comparative Toxicogenomics Database (CTD) and Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) disease database collection of Ulcerative Colitis target genes

the drug-disease protein target gene was obtained by intersecting the two and to display the results by Cytoscape software

through the algorithm of network topology to screen out the key target genes

Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on key target genes using Gene Ontology Enrichment Analysis Softword Toolkit (GOEAST) and The Database for Annotation

Visualization and Integrated Discovery (DAVID) online tools

analyze the mechanism of Sishenwan in preventing and treating Ulcerative Colitis combined with relevant literature.

Result:

There are 182 active ingredients and 611 predicted targets in Sishen Wans

914 known disease targets related to the occurrence and development of Ulcerative Colitis were retrieved through the disease database

it was concluded that the effect of Sishenwan on Ulcerative Colitis mainly involves steroid hormone-mediated signal pathway

exogenous metabolic process

positive regulation of transcription of RNA polymerase II promoter

lipid metabolic process

detoxification of cell oxidant

signal transduction and other biological functions

and participates in arachidonic acid

drug metabolism-cytochrome P450

cytochrome P450 for xenobiotics

chemical carcinogenesis and other key signal pathways.

Conclusion:

Sishenwan has the characteristics of multi-target

multi-channel and multi-level in the treatment of Ulcerative Colitis. Its multiple signal pathways are directly or indirectly related

participating in lipid protein metabolism

drug metabolism and anti-cancer mechanism

etc. It exerts its efficacy through comprehensive intervention on the digestive system

circulatory system

immune system and other multiple systems of the body

thus being consistent with the comprehensive effect mechanism of Ulcerative Colitis induced by multiple factors.

关键词

四神丸溃疡性结肠炎网络药理学生物信息学信号通路

Keywords

Sishenwanulcereative colitisnetwork pharmacologybioinformaticssignal pathway

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