Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique

Abstract This study explores the mechanisms of Astragaloside A (AS-A), a significant active ingredient in Astragalus, This traditional Chinese medicine is both a medication and a food, combating lung adenocarcinoma using network pharmacology, molecular docking, molecular dynamics, and experimental v...

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Main Authors: Jian Ding, Qian Xue, Weizhen Guo, Gang Cheng, Lu Zhang, Tantan Huang, Di Wu, Jiabing Tong, Cheng Yang, Yating Gao, Zegeng Li
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-94793-6
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author Jian Ding
Qian Xue
Weizhen Guo
Gang Cheng
Lu Zhang
Tantan Huang
Di Wu
Jiabing Tong
Cheng Yang
Yating Gao
Zegeng Li
author_facet Jian Ding
Qian Xue
Weizhen Guo
Gang Cheng
Lu Zhang
Tantan Huang
Di Wu
Jiabing Tong
Cheng Yang
Yating Gao
Zegeng Li
author_sort Jian Ding
collection DOAJ
description Abstract This study explores the mechanisms of Astragaloside A (AS-A), a significant active ingredient in Astragalus, This traditional Chinese medicine is both a medication and a food, combating lung adenocarcinoma using network pharmacology, molecular docking, molecular dynamics, and experimental validation. A protein–protein interaction (PPI) network was developed, identifying 10 key targets, including STAT3 and AKT1. GO and KEGG enrichment analyses indicated that these targets primarily participated in biological processes and pathways, including oxidative stress and the PI3K-Akt signalling pathway. Molecular docking and dynamic simulation evaluated AS-A's binding mode and stability with key targets. In molecular docking, 14 key targets of the HIF-1 signalling pathway had different binding energies with AS-A, such as the binding energy of PIK3R1 being -9.3. Kinetic simulations indicated the stability of the protein–ligand complex, as evidenced by RMSD values ranging from 0.2 to 0.4 nm. RMSF analysis showed that the protein residue flexibility characteristics were stable, the Rg values were stable, the number of hydrogen bonds was 10–20, and the solvent-accessible surface area was stable. Cell experiments showed that AS-A could regulate the expression of key signalling molecules such as STAT3 and AKT in lung adenocarcinoma models. This study provides insights into the mechanism of AS-A in treating lung adenocarcinoma. It proposes a new direction for anticancer research in traditional Chinese medicines, especially medications and foods.
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spelling doaj-art-41661586859b44e9bae8bdcaa25c1ad02025-08-20T02:28:03ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-94793-6Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation techniqueJian Ding0Qian Xue1Weizhen Guo2Gang Cheng3Lu Zhang4Tantan Huang5Di Wu6Jiabing Tong7Cheng Yang8Yating Gao9Zegeng Li10Department of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineDepartment of First Affiliated Hospital of Anhui University of Chinese MedicineAbstract This study explores the mechanisms of Astragaloside A (AS-A), a significant active ingredient in Astragalus, This traditional Chinese medicine is both a medication and a food, combating lung adenocarcinoma using network pharmacology, molecular docking, molecular dynamics, and experimental validation. A protein–protein interaction (PPI) network was developed, identifying 10 key targets, including STAT3 and AKT1. GO and KEGG enrichment analyses indicated that these targets primarily participated in biological processes and pathways, including oxidative stress and the PI3K-Akt signalling pathway. Molecular docking and dynamic simulation evaluated AS-A's binding mode and stability with key targets. In molecular docking, 14 key targets of the HIF-1 signalling pathway had different binding energies with AS-A, such as the binding energy of PIK3R1 being -9.3. Kinetic simulations indicated the stability of the protein–ligand complex, as evidenced by RMSD values ranging from 0.2 to 0.4 nm. RMSF analysis showed that the protein residue flexibility characteristics were stable, the Rg values were stable, the number of hydrogen bonds was 10–20, and the solvent-accessible surface area was stable. Cell experiments showed that AS-A could regulate the expression of key signalling molecules such as STAT3 and AKT in lung adenocarcinoma models. This study provides insights into the mechanism of AS-A in treating lung adenocarcinoma. It proposes a new direction for anticancer research in traditional Chinese medicines, especially medications and foods.https://doi.org/10.1038/s41598-025-94793-6Astragaloside ALung adenocarcinomaNetwork pharmacologyRegulatory mechanismMedicinal and edible plants
spellingShingle Jian Ding
Qian Xue
Weizhen Guo
Gang Cheng
Lu Zhang
Tantan Huang
Di Wu
Jiabing Tong
Cheng Yang
Yating Gao
Zegeng Li
Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
Scientific Reports
Astragaloside A
Lung adenocarcinoma
Network pharmacology
Regulatory mechanism
Medicinal and edible plants
title Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
title_full Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
title_fullStr Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
title_full_unstemmed Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
title_short Mechanism of astragaloside A against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
title_sort mechanism of astragaloside a against lung adenocarcinoma based on network pharmacology combined with molecular dynamics simulation technique
topic Astragaloside A
Lung adenocarcinoma
Network pharmacology
Regulatory mechanism
Medicinal and edible plants
url https://doi.org/10.1038/s41598-025-94793-6
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