当归四逆汤治疗肝细胞癌作用机制的网络药理学分析

刘泽宇; 万宇翔; 黄金昶

doi:10.13422/j.cnki.syfjx.20200124

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当归四逆汤治疗肝细胞癌作用机制的网络药理学分析

数据挖掘 | 更新时间：2021-02-09

- 当归四逆汤治疗肝细胞癌作用机制的网络药理学分析
- Network Pharmacology Study on Mechanism of Danggui Sinitang in Treating Hepatocellular Carcinoma
- 中国实验方剂学杂志 2020年26卷第6期页码：185-192
- 作者机构：
  
  北京中医药大学　第三附属医院，北京　 100029
- 作者简介：
  
  [第一作者]　刘泽宇，在读博士，从事中西医结合防治肿瘤研究，E-mail：13718560318@139.com
  *黄金昶，博士生导师，主任医师，从事中西医结合防治肿瘤研究，E-mail：zryhhuang@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81573736);北京市自然科学基金面上项目(7172128);北京中医药大学研究生自主课题项目(2019-JYB-XS-245)
- DOI：10.13422/j.cnki.syfjx.20200124
  中图分类号： R22; R242; R2-031;R285.5
- 收稿日期：2019-06-17，
  
  网络出版日期：2019-09-18，
  
  纸质出版日期：2020-03-20
- 稿件说明：
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刘泽宇, 万宇翔, 黄金昶. 当归四逆汤治疗肝细胞癌作用机制的网络药理学分析[J]. 中国实验方剂学杂志, 2020,26(6):185-192.

Ze-yu LIU, Yu-xiang WAN, Jin-chang HUANG. Network Pharmacology Study on Mechanism of Danggui Sinitang in Treating Hepatocellular Carcinoma[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 185-192.
刘泽宇, 万宇翔, 黄金昶. 当归四逆汤治疗肝细胞癌作用机制的网络药理学分析[J]. 中国实验方剂学杂志, 2020,26(6):185-192. DOI： 10.13422/j.cnki.syfjx.20200124.

Ze-yu LIU, Yu-xiang WAN, Jin-chang HUANG. Network Pharmacology Study on Mechanism of Danggui Sinitang in Treating Hepatocellular Carcinoma[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 185-192. DOI： 10.13422/j.cnki.syfjx.20200124.

摘要

目的：

通过对当归四逆汤的网络药理学分析，探讨当归四逆汤治疗肝细胞癌的潜在抗肿瘤靶点及作用机制，为后续研究提供有针对性的指导。

方法：

利用Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)网站及SwissTargetPrediction网站建立当归四逆汤有效成分及靶点数据库，利用Comparative Toxicogenomics Database(CTD)，Therapeutic Target Database(TTD)，Human Phenotype Ontology(HPO)网站建立肝细胞癌相关靶点数据库，并与当归四逆汤靶点数据库相匹配。在匹配结果的基础上，应用STRING网站分析靶标之间的相互作用，并利用The Database for Annotation

Visualization and Integrated Discovery(DAVID)网站进行基因本体论(gene ontology，GO)生物学过程分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析，运用Cytoscape 3.6.0软件进行网络分析。

结果：

共发现当归四逆汤治疗肝细胞癌的56个可能的重要靶点，经GO富集分析得到106个细胞生物学过程，经KEGG富集分析得到23个相关通路，其中主要包括TNF信号通路，FoxO信号通路，Toll样受体信号通路，p53信号通路，磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路，腺苷酸激活蛋白激酶(AMPK)信号通路，两面神激酶(JAK)/信号传导及转录激活因子(STAT)信号通路等。

结论：

当归四逆汤对肝细胞癌的治疗作用可能是多靶点、多途径、多层次的。并且可以推测槲皮素和山柰酚可能是其中比较重要的2个有效成分，PI3K/Akt信号通路和MAPK信号通路可能是本方发挥作用比较重要的两条信号通路。本研究不仅有助于更好地理解当归四逆汤抗肝细胞癌的作用机制，而且提供了利用网络药理学开发新的中医药候选药物的策略。

Abstract

Objective:

This paper aims to explore the potential anti-neoplasm targets and mechanism of Danggui Sinitang on hepatocellular carcinoma by analyzing the prescription of Danggui Sinitang with the method of network pharmacology

in order to provide targeted guidance for further studies.

Method:

The Traditional Chinese Medicine System Platform (TCMSP) and SwissTargetPrediction database were adopted to establish the database of Danggui Sinitang' s effective ingredients and targets. The Comparative Toxicogenomics Database (CTD)

Therapeutic Target Database (TTD)

and Human Phenotype Ontology (HPO) were used to build the hepatocellular carcinoma target database

which was then matched with Danggui Sinitang' s target database. Based on the matching results

STRING database was applied to analyze the interactions between the targets and the Database for Annotation

Visualization and Integrated Discovery (DAVID) was utilized for the enrichment analysis on gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then Cytoscape 3.6.0 software was used for networks analysis.

Result:

A total of 56 significant targets of Danggui Sinitang were found for treatment of hepatocellular carcinoma. The 106 cellular biological processes were obtained through GO biological process enrichment analysis and 23 related pathways were obtained by KEGG enrichment analysis

mainly including TNF signaling pathway

FoxO signaling pathway

Toll-like receptor signaling pathway

p53 signaling pathway

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

AMP activated protein kinase(AMPK) signaling pathway

Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathway

et al.

Conclusion:

The therapeutic effect of Danggui Sinitang on hepatocellular carcinoma may be multi-target

multi-channel and multi-level. It can be inferred that quercetin and kaempferol may be two important active components

and PI3K/Akt signaling pathway and MAPK signaling pathway may be two important signaling pathways. This study not only makes a contribution to a better understanding of the anti-hepatocellular carcinoma mechanism of Danggui Sinitang

but also proposes a strategy to develop new TCM candidates at a network pharmacology level.

关键词

Keywords

references

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