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基于网络药理学的茵陈蒿汤治疗丙型肝炎作用的药效机制的生物信息学研究。

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology.

机构信息

Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11 of North Three-ring East Road, Chao Yang District, Beijing, China.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou City, China.

出版信息

BMC Complement Med Ther. 2020 Feb 12;20(1):50. doi: 10.1186/s12906-020-2823-y.

Abstract

BACKGROUND

Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders.

METHODS

In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein-protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses.

RESULTS

This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C.

CONCLUSION

The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.

摘要

背景

全球有超过 1.7 亿人感染丙型肝炎病毒,这是肝硬化和肝细胞癌的主要病因。茵陈蒿汤(YCHD)是一种由三种草药组成的经典方剂。该方剂在中国长期用于临床治疗急性和慢性传染性肝炎及其他肝胆湿热积聚疾病。

方法

本研究通过 Cytoscape 3.6.1 识别出 32 种活性成分和 200 种丙型肝炎蛋白,建立了一个复方预测靶点网络和一个丙型肝炎蛋白-蛋白相互作用网络。然后,我们系统地分析了 YCHD 治疗丙型肝炎的潜在靶点。最后,应用分子对接验证关键靶点。此外,我们还通过京都基因与基因组百科全书和基因本体分析对预测靶点的作用机制进行了分析。

结果

本研究采用网络药理学方法,主要包括靶点预测、网络构建、模块检测、功能富集分析和分子对接,系统研究了 YCHD 治疗丙型肝炎的作用机制。YCHD 治疗丙型肝炎的靶点主要涉及 PIK3CG、CASP3、BCL2、CASP8 和 MMP1。模块和通路富集分析表明,YCHD 可能影响多种生物学途径,包括 TNF 信号通路、Ras 信号通路、PI3K-Akt 信号通路、FoxO 信号通路和癌症通路,这些途径在丙型肝炎的发病机制中起着重要作用。

结论

本研究初步验证了 YCHD 治疗丙型肝炎的基本药理作用及相关机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac2b/7076901/5b2e7b5feb30/12906_2020_2823_Fig1_HTML.jpg

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