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Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation

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Abstract

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein–protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

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Availability of data and materials

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

A. annua :

Artemisia annua L.

ADME:

Absorption, distribution, metabolism, excretion

AGEs:

Advanced glycation end products

AMI:

Acute myocardial infarction

BP:

Biological process

BC:

Betweenness centrality

CC:

Cellular component

CVD:

Cardiovascular disease

DC:

Degree centrality

DL:

Drug-likeness

DTBT:

Door-to-balloon time

DTNT:

Door-to-needle time

EC:

Eigenvector centrality

EF:

Ejection fraction

FS:

Fractional shortening

GO:

Gene ontology

I/R:

Ischemia–reperfusion

KEGG:

Kyoto encyclopedia of genes and genomes

LAC:

Local average-connectivity-based centrality

LAD:

Left anterior descending coronary artery

LV:

Left Ventricular function

LVEDP:

LV end-diastolic pressure

LVSP:

Peak systolic LV pressure

MF:

Molecular function

MMP-2:

Matrix metalloproteinase-2

MPTPs:

Mitochondrial permeability transition pores

NC:

Network centrality

OB:

Oral Bioavailability

OMIM:

Online Mendelian inheritance in man

PPI:

Protein–protein interaction

STRING:

Search tool for the retrieval of interacting genes database

TCM:

Traditional Chinese medicine

TCMSP:

Traditional Chinese medicine systems pharmacology database and analysis platform

TGF-β1:

Transforming growth factor-β1

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Acknowledgements

Deng Liang and Duan Yixuan contributed to the preliminary data analysis, interpretation, and manuscript writing. Liu Chang, Sun Jingjing and Zhao Sihai participated in the manuscript submission and editing. Deng Jie participated in research design. All authors contributed to the final approval of manuscript.

Funding

This study was supported by Shannxi Social Development Funding (grant No.2017SF-134) and Shannxi Science Funding (grant No.2020JQ-553) and Xi’an Jiaotong University Funding (grant No.YXJLRH2022073).

Author information

Authors and Affiliations

  1. School of Medicine, Shanxi Datong University, Datong, 037009, Shanxi, China

    Deng Liang

  2. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Duan Yixuan, Liu Chang, Sun Jingjing & Deng Jie

  3. Laboratory Animal Center, Xi’an Jiaotong University School of Medicine, Xi’an, 710061, Shaanxi, China

    Zhao Sihai

Authors
  1. Deng Liang
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  2. Duan Yixuan
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  3. Liu Chang
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  4. Sun Jingjing
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  5. Zhao Sihai
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  6. Deng Jie
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Contributions

Deng Liang and Duan Yixuan contributed to the preliminary data analysis, interpretation, and manuscript writing. Liu Chang, Sun Jingjing and Zhao Sihai participated in the manuscript submission and editing. Deng Jie participated in research design. All authors contributed to the final approval of manuscript.

Corresponding author

Correspondence to Deng Jie.

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The authors declare no competing interests.

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The authors declare that there is no conflict of interest.

Ethical approval and consent to participate.

This research was approved by Xi’an Jiaotong University Committee on Animal Care (Shaanxi, China).

Research involving human participants or Animals

All experiments were carried out in accordance with the guide for the care and use of Laboratory Animals (Department of Health and Human Services, Publication No. [NIH] 86–23), and were approved by Xi’an Jiaotong University Committee on Animal Care (Shaanxi, China).

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Liang, D., Yixuan, D., Chang, L. et al. Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10750-3

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