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Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation

This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Tr...

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Autores principales: Shi, Li, Deng, Yuanjun, Luo, Denggui, Li, Lei, Kuang, Xuyi, Qi, Airong, Fu, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662869/
https://www.ncbi.nlm.nih.gov/pubmed/37478256
http://dx.doi.org/10.1097/MD.0000000000034446
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author Shi, Li
Deng, Yuanjun
Luo, Denggui
Li, Lei
Kuang, Xuyi
Qi, Airong
Fu, Bo
author_facet Shi, Li
Deng, Yuanjun
Luo, Denggui
Li, Lei
Kuang, Xuyi
Qi, Airong
Fu, Bo
author_sort Shi, Li
collection PubMed
description This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Swiss Target Prediction database. The NS targets were retrieved from Genecards, OMIM and Drugbank databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interaction network analysis, and the core targets were identified through topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed in the Metascape platform. Finally, molecular docking and molecular dynamics simulation were performed for further validation. The network analysis showed that 109 active ingredients of LGZGD were associated with 105 targets in NS. The key active ingredients (quercetin, kaempferol, naringenin, licochalcone A, formononetin, beta-sitosterol) and the core targets (IL6, AKT1, TNF, VEGFA, TP53, JUN, IL1B, CASP3, EGFR, and STAT3) were further identified. Enrichment analysis indicated that multiple biological processes and pathways, including AGE-RAGE, PI3K-Akt, JAK-STAT, and HIF-1 signaling pathways, might be regulated by LGZGD in the treatment of NS. Molecular docking and molecular dynamics simulation results further indicated that the key active ingredients of LGZGD could stably bind to the core targets through hydrogen bonding and hydrophobic interaction. This study demonstrates that the active ingredients of LGZGD may regulate multiple targets, biological processes and signaling pathways in NS. Our findings may provide a theoretical basis for further studies on LGZGD in the treatment of NS.
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spelling pubmed-106628692023-07-21 Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation Shi, Li Deng, Yuanjun Luo, Denggui Li, Lei Kuang, Xuyi Qi, Airong Fu, Bo Medicine (Baltimore) 3800 This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Swiss Target Prediction database. The NS targets were retrieved from Genecards, OMIM and Drugbank databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interaction network analysis, and the core targets were identified through topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed in the Metascape platform. Finally, molecular docking and molecular dynamics simulation were performed for further validation. The network analysis showed that 109 active ingredients of LGZGD were associated with 105 targets in NS. The key active ingredients (quercetin, kaempferol, naringenin, licochalcone A, formononetin, beta-sitosterol) and the core targets (IL6, AKT1, TNF, VEGFA, TP53, JUN, IL1B, CASP3, EGFR, and STAT3) were further identified. Enrichment analysis indicated that multiple biological processes and pathways, including AGE-RAGE, PI3K-Akt, JAK-STAT, and HIF-1 signaling pathways, might be regulated by LGZGD in the treatment of NS. Molecular docking and molecular dynamics simulation results further indicated that the key active ingredients of LGZGD could stably bind to the core targets through hydrogen bonding and hydrophobic interaction. This study demonstrates that the active ingredients of LGZGD may regulate multiple targets, biological processes and signaling pathways in NS. Our findings may provide a theoretical basis for further studies on LGZGD in the treatment of NS. Lippincott Williams & Wilkins 2023-07-21 /pmc/articles/PMC10662869/ /pubmed/37478256 http://dx.doi.org/10.1097/MD.0000000000034446 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
spellingShingle 3800
Shi, Li
Deng, Yuanjun
Luo, Denggui
Li, Lei
Kuang, Xuyi
Qi, Airong
Fu, Bo
Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title_full Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title_fullStr Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title_full_unstemmed Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title_short Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
title_sort exploration of the possible mechanisms of ling gui zhu gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation
topic 3800
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662869/
https://www.ncbi.nlm.nih.gov/pubmed/37478256
http://dx.doi.org/10.1097/MD.0000000000034446
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