Abstract
To investigate the molecular mechanism of Astragalus membranaceus (AM) in alleviating silicosis fibrosis using bioinformatics and in vitro experiments. Active ingredients of AM and their corresponding targets were retrieved from the TCMSP and SwissTargetPrediction databases. These ingredients were screened based on oral bioavailability (OB ≥ 30%), drug-likeness (DL ≥ 0.18), and Lipinski’s Rule of Five, which serves as a standard for identifying drug-like molecules with favorable pharmacokinetic properties in network pharmacology. Silicosis-related targets were collected from DisGENET, GeneCards, and the Comparative Toxicogenomics Database (CTD). Common targets were identified for protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Core ingredients and targets were selected through topological analysis in Cytoscape and subsequently validated using molecular docking (AutoDock), immunofluorescence and RT-qPCR assays. Eight main active ingredients of AM were identified, along with 236 AM targets and 7,706 silicosis targets, resulting in 113 shared targets. Further screening revealed three key ingredients: Quercetin, isorhamnetin, and kaempferol, as well as seven core targets: AKT1, CASP3, PTGS2, MMP9, ESR1, JUN and EGFR. The primary pathways involved included PI3K-AKT, IL-17, and MAPK. Molecular docking analyses indicated that MMP9 and EGFR exhibited higher binding energies with Quercetin. In vitro immunofluorescence results demonstrated that Quercetin downregulated the expression of MMP9, EGFR, and α-SMA in silicotic fibroblasts. Additionally, qRT-PCR assays confirmed that the Quercetin alleviated SiO2-induced fibrotic process by suppressing PI3K-AKT pathway in the anti-fibrotic process. Quercetin, the key active ingredient of AM, exerts its anti-silicosis effect by inhibiting the expression of EGFR, MMP9 and the PI3K/Akt pathway.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ECM:
-
Extracellular matrix
- TCM:
-
Traditional Chinese medicine
- AM:
-
Astragalus membranaceus
- NP:
-
Network pharmacology
- GO:
-
Gene ontology
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- PPI:
-
Protein‒protein interaction
- BP:
-
Biological process
- CC:
-
Cytological component
- MF:
-
Molecular function
- AKT1:
-
RAC-alpha serine/threonine-protein kinase
- CASP3:
-
Caspase-3
- EGFR:
-
Epidermal growth factor receptor
- MMP9:
-
Matrix metalloproteinase 9
- ESR1:
-
Estrogen receptor
- JUN:
-
Jun proto-oncogene, AP-1 transcription factor subunit
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Acknowledgements
We express our gratitude to all the authors for their assistance and support.
Funding
This work was supported by the National Natural Science Foundation of China (82271626, 82160088, 82560099), Ningxia Hui Autonomous Region Youth Top Talent Training Project. Chinese Academy of Sciences “Western Young Scholars” project. China Postdoctoral Science Foundation (2023MD734192), Ningxia Natural Science Foundation (2025AAC050075, 2022AAC03128, 2022AAC05025), Ningxia Key Research and Development Projects (2020BFH02003, 2021BEG02030), Open competition mechanism to select the best candidates for key research projects of Ningxia Medical University (XJKF230106).
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Y(Y.A.N.) and L.were responsible for most of the data collection and conducted most of the experiments. G and C have made contributions to some data collection and data integration. W and Z(Z.H.N.)made contributions to some experimental work. Y and Z(Z.W.Y.) participated in the drafting of the manuscript. All authors have reviewed the subsequent versions of the manuscript and have read and approved the final version submitted.
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Yang, A., Luo, X., Guo, Y. et al. The network pharmacology prediction and experiment validation of Astragalus membranaceus for alleviating silicosis fibrosis via decreasing MMP9 and EGFR expression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42544-6
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DOI: https://doi.org/10.1038/s41598-026-42544-6
