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

BMC Complementary Medicine and Therapies · 6 authors, 4 centres

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TL;DR

Using network pharmacology, molecular docking, GEO database validation, and in vitro experiments in LPS-induced Raw264.7 macrophages, this study identified quercetin and naringenin from Folium Artemisiae argyi as bioactive compounds that suppress MMP9 and pro-inflammatory cytokines IL-1β and IL-6.

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Eight hub genes were identified, with IL-1β, VEGFA, and MMP9 in the fluid shear stress and atherosclerosis pathway highlighted as key targets. GEO database validation (GSE71226, GSE9128) confirmed IL-1β and MMP9 were upregulated while VEGFA was downregulated in disease samples versus controls. Molecular docking indicated quercetin has favorable interactivity with MMP9.

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other

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cardiology

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ORIGINAL PAPER

PMC10601115

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

BMC Complementary Medicine and Therapies

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ABSTRACT

Abstract 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. Keywords: Folium Artemisiae argyi, Atherosclerotic cardiovascular disease, Network pharmacology, Anti-inflammation, Quercetin, Naringenin

CITATION EXPORT

Lei Zhang, Zhihui Yang, Xinyi Li et al.. 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. BMC Complementary Medicine and Therapies. (2023). https://doi.org/10.1186/s12906-023-04223-1

AUTHORS

6 · 4 CENTRES

Lei Zhang, Zhihui Yang, Xinyi Li, Yunqing Hua, Guanwei Fan, Feng He

1Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang, 438000 China
2Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University, Huanggang, 438000 China
3First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
4Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China