基于网络药理学与分子对接和体外实验探讨青蒿治疗脓肿分枝杆菌感染的研究

石茜; 杨子晨; 张建; 廖丹溪; 张一鸣

doi:10.16016/j.2097-0927.202211177

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基于网络药理学与分子对接和体外实验探讨青蒿治疗脓肿分枝杆菌感染的研究

药学 | 更新时间：2026-01-09

- 基于网络药理学与分子对接和体外实验探讨青蒿治疗脓肿分枝杆菌感染的研究
- Artemisia annua L. in treatment for Mycobacterium abscessus infection based on network pharmacology, molecular docking and in vitro experiments
- 陆军军医大学学报 2023年45卷第13期页码：1463-1475
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院整形美容外科
  2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院全军烧伤研究所，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
  
  [张一鸣，E-mail：zhangyiming@tmmu.edu.cnZHANG Yiming, E-mail: zhangyiming@tmmu.edu.cn
- 基金信息：
  
  国家自然科学基金青年科学基金项目(82002051);重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0655);陆军军医大学优秀人才库资助项目(2019R031)
- DOI：10.16016/j.2097-0927.202211177
  中图分类号： R285;R319;R632.5
- 收稿：2022-11-24，
  
  修回：2023-01-30，
  
  纸质出版：2023-07-15
- 稿件说明：
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石茜, 杨子晨, 张建, 等. 基于网络药理学与分子对接和体外实验探讨青蒿治疗脓肿分枝杆菌感染的研究[J]. 陆军军医大学学报, 2023,45(13):1463-1475.

Xi SHI, Zichen YANG, Jian ZHANG, et al. Artemisia annua L. in treatment for Mycobacterium abscessus infection based on network pharmacology, molecular docking and in vitro experiments[J]. Journal of Army Medical University, 2023, 45(13): 1463-1475.
石茜, 杨子晨, 张建, 等. 基于网络药理学与分子对接和体外实验探讨青蒿治疗脓肿分枝杆菌感染的研究[J]. 陆军军医大学学报, 2023,45(13):1463-1475. DOI： 10.16016/j.2097-0927.202211177.

Xi SHI, Zichen YANG, Jian ZHANG, et al. Artemisia annua L. in treatment for Mycobacterium abscessus infection based on network pharmacology, molecular docking and in vitro experiments[J]. Journal of Army Medical University, 2023, 45(13): 1463-1475. DOI： 10.16016/j.2097-0927.202211177.

摘要

目的

结合网络药理学、分子对接技术及其体外实验，探讨青蒿应用于脓肿分枝杆菌感染的作用机制。

方法

从中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform

TCMSP)系统中获得青蒿的活性成分，使用PharmMapper、SwissTargetPrediction预测青蒿作用靶点。从GeneCards数据库和OMIM数据库获得脓肿分枝杆菌感染相关靶点。获得共同靶点后，使用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用(protein-protein interaction

PPI)网络图。使用Metascape数据库进行基因本体(gene ontology

GO)功能富集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。筛选出青蒿主要潜在活性成分与核心靶点进行分子对接。将青蒿提取物及筛选出的青蒿主要潜在活性成分进行体外实验，探究其最小抑菌浓度，与常用抗脓肿分枝杆菌抗生素的体外联合作用，及其对脓肿分枝杆菌活力的影响。

结果

共发现48个青蒿靶点参与脓肿分枝杆菌感染的发病机制。MMP9、MAPK3、CASP3、IL2、CASP1、MMP2共6个靶点预测为通过青蒿治疗该疾病的核心靶点。KEGG富集分析表明，青蒿可能通过IL-17信号通路、中性粒细胞胞外陷阱形成、Toll样受体信号通路、肿瘤坏死因子信号通路、MAPK信号通路等炎症和免疫相关信号通路治疗该疾病。分子对接结果表明，青蒿与这些核心靶点具有高亲和力。筛选出柽柳黄素、艾黄素、双氢青蒿素、青蒿提取物对脓肿分枝杆菌具有体外抑菌活性，单独药物的最小抑菌浓度(MIC)值分别为200、100、100、100 μg/mL。联合使用青蒿提取物后，克拉霉素、阿奇霉素、阿米卡星、亚胺培南、头孢西丁的MIC值都较单独使用时下降，下降倍数为2~8倍。

结论

青蒿可能通过多靶点和多途径作用于脓肿分枝杆菌感染，其对脓肿分枝杆菌具有体外抑菌作用并与部分抗生素产生协同作用。

Abstract

Objective

To explore the mechanism of

Artemisia annua

L. (

A. annua

) in treatment of

Mycobacterium abscessus

(

M. abscessus

) infection with aid of network pharmacology and molecular docking.

Methods

The active components of

A. annua

were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) system

and the targets of

A. annua

were predicted using PharmMapper and SwissTargetPrediction. Targets related to

M. abscessus

infection were obtained from GeneCards database and OMIM database. After obtaining the common targets of them

a target protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Then Metascape database was employed to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main potential active components of

A. annua

were screened out for molecular docking with the core targets. The extracts of

A. annua

and the main potential active ingredients screened out were tested

in vitro

to explore its minimum inhibitory concentration (MIC)

its combined efficacy with common anti-

M. abscessus

antibiotics

in vitro

and its effect on the viability of

M. abscessus

Results

A total of 48 targets of

A. annua

were found to be involved in the pathogenesis of

M. abscessus

infection. A total of 6 targets

MMP9

MAPK3

CASP3

IL2

CASP1

and MMP2

were predicted to be the core targets of

A. annua

in the treatment of this disease. KEGG enrichment analysis showed that

A. annua

may treat this disease through IL-17 signaling pathway

neutrophil extracellular trap formation

Toll-like receptor signaling pathway

tumor necrosis factor signaling pathway

MAPK signaling pathway and other inflammatory and immune-related signaling pathways. Molecular docking results indicated that

A. annua

had a high affinity with these core targets. Tamarixetin

artemetin

dihydroartemisinin and

Artemisia annua

L. were screened to have antibacterial activity against

M. abscessus

in vitro

with a MIC value of 200

100

100 and 100 μg/mL

respectively. After combined with the exacts of

A. annua

the MIC value of clarithromycin

azithromycin

amikacin

imipenem

and cefoxitin was all decreased than that of their single use

with a declining multiple ranging from 2 to 8 times.

Conclusion

A. annua

may act on

M. abscessus

infection through multiple targets and multiple pathways. It has antibacterial effect

in vitro

and shows a synergistic effect with some antibiotics against the bacteria.

关键词

Keywords

references

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