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Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation

Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes...

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Autores principales: Zhang, Lei, Yang, Zhihui, Li, Xinyi, Hua, Yunqing, Fan, Guanwei, He, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601115/
https://www.ncbi.nlm.nih.gov/pubmed/37880698
http://dx.doi.org/10.1186/s12906-023-04223-1
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author Zhang, Lei
Yang, Zhihui
Li, Xinyi
Hua, Yunqing
Fan, Guanwei
He, Feng
author_facet Zhang, Lei
Yang, Zhihui
Li, Xinyi
Hua, Yunqing
Fan, Guanwei
He, Feng
author_sort Zhang, Lei
collection PubMed
description Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1β /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1β could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1β were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9. Practical Applications Artemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04223-1.
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spelling pubmed-106011152023-10-27 Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation Zhang, Lei Yang, Zhihui Li, Xinyi Hua, Yunqing Fan, Guanwei He, Feng BMC Complement Med Ther Research Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1β /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1β could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1β were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9. Practical Applications Artemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04223-1. BioMed Central 2023-10-25 /pmc/articles/PMC10601115/ /pubmed/37880698 http://dx.doi.org/10.1186/s12906-023-04223-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Lei
Yang, Zhihui
Li, Xinyi
Hua, Yunqing
Fan, Guanwei
He, Feng
Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title_full Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title_fullStr Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title_full_unstemmed Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title_short Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
title_sort anti-atherosclerotic effects of naringenin and quercetin from folium artemisiae argyi by attenuating interleukin-1 beta (il-1β)/ matrix metalloproteinase 9 (mmp9): network pharmacology-based analysis and validation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601115/
https://www.ncbi.nlm.nih.gov/pubmed/37880698
http://dx.doi.org/10.1186/s12906-023-04223-1
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