Cargando…

Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking

Quercetin (QUE), a health supplement, can improve renal function in diabetic nephropathy (DN) rats by ameliorating podocyte injury. Its clinical trial for renal insufficiency in advanced diabetes (NCT02848131) is currently underway. This study aimed to investigate the mechanism of QUE protecting aga...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Xiaoqin, Hao, Chenxia, Yu, Meixiang, Zhang, Zhaokang, Huang, Jingjing, Yang, Wanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126727/
https://www.ncbi.nlm.nih.gov/pubmed/35615688
http://dx.doi.org/10.1155/2022/7291434
_version_ 1784712191847432192
author Ma, Xiaoqin
Hao, Chenxia
Yu, Meixiang
Zhang, Zhaokang
Huang, Jingjing
Yang, Wanhua
author_facet Ma, Xiaoqin
Hao, Chenxia
Yu, Meixiang
Zhang, Zhaokang
Huang, Jingjing
Yang, Wanhua
author_sort Ma, Xiaoqin
collection PubMed
description Quercetin (QUE), a health supplement, can improve renal function in diabetic nephropathy (DN) rats by ameliorating podocyte injury. Its clinical trial for renal insufficiency in advanced diabetes (NCT02848131) is currently underway. This study aimed to investigate the mechanism of QUE protecting against podocyte injury to attenuate DN through network pharmacology, microarray data analysis, and molecular docking. QUE-associated targets, genes related to both DN, and podocyte injury were obtained from different comprehensive databases and were intersected and analyzed to obtain mapping targets. Candidate targets were identified by constructing network of protein-protein interaction (PPI) of mapping targets and ranked to obtain key targets. The major pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) term enrichment analysis of candidate targets via ClueGO plug-in and R project software, respectively. Potential receptor-ligand interactions between QUE and key targets were evaluated via Autodocktools-1.5.6. 41. Candidate targets, of which three key targets (TNF, VEGFA, and AKT1), and the major AGE-RAGE signaling pathway in diabetic complications were ascertained and associated with QUE against podocyte injury in DN. Molecular docking models showed that QUE could closely bind to the key targets. This study revealed that QUE could protect against podocyte injury in DN through the following mechanisms: downregulating inflammatory cytokine of TNF, reducing VEGF-induced vascular permeability, inhibiting apoptosis by stimulating AKT1 phosphorylation, and suppressing the AGE-induced oxidative stress via the AGE-RAGE signaling pathway.
format Online
Article
Text
id pubmed-9126727
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-91267272022-05-24 Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking Ma, Xiaoqin Hao, Chenxia Yu, Meixiang Zhang, Zhaokang Huang, Jingjing Yang, Wanhua Evid Based Complement Alternat Med Research Article Quercetin (QUE), a health supplement, can improve renal function in diabetic nephropathy (DN) rats by ameliorating podocyte injury. Its clinical trial for renal insufficiency in advanced diabetes (NCT02848131) is currently underway. This study aimed to investigate the mechanism of QUE protecting against podocyte injury to attenuate DN through network pharmacology, microarray data analysis, and molecular docking. QUE-associated targets, genes related to both DN, and podocyte injury were obtained from different comprehensive databases and were intersected and analyzed to obtain mapping targets. Candidate targets were identified by constructing network of protein-protein interaction (PPI) of mapping targets and ranked to obtain key targets. The major pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) term enrichment analysis of candidate targets via ClueGO plug-in and R project software, respectively. Potential receptor-ligand interactions between QUE and key targets were evaluated via Autodocktools-1.5.6. 41. Candidate targets, of which three key targets (TNF, VEGFA, and AKT1), and the major AGE-RAGE signaling pathway in diabetic complications were ascertained and associated with QUE against podocyte injury in DN. Molecular docking models showed that QUE could closely bind to the key targets. This study revealed that QUE could protect against podocyte injury in DN through the following mechanisms: downregulating inflammatory cytokine of TNF, reducing VEGF-induced vascular permeability, inhibiting apoptosis by stimulating AKT1 phosphorylation, and suppressing the AGE-induced oxidative stress via the AGE-RAGE signaling pathway. Hindawi 2022-05-16 /pmc/articles/PMC9126727/ /pubmed/35615688 http://dx.doi.org/10.1155/2022/7291434 Text en Copyright © 2022 Xiaoqin Ma et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ma, Xiaoqin
Hao, Chenxia
Yu, Meixiang
Zhang, Zhaokang
Huang, Jingjing
Yang, Wanhua
Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title_full Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title_fullStr Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title_full_unstemmed Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title_short Investigating the Molecular Mechanism of Quercetin Protecting against Podocyte Injury to Attenuate Diabetic Nephropathy through Network Pharmacology, MicroarrayData Analysis, and Molecular Docking
title_sort investigating the molecular mechanism of quercetin protecting against podocyte injury to attenuate diabetic nephropathy through network pharmacology, microarraydata analysis, and molecular docking
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126727/
https://www.ncbi.nlm.nih.gov/pubmed/35615688
http://dx.doi.org/10.1155/2022/7291434
work_keys_str_mv AT maxiaoqin investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking
AT haochenxia investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking
AT yumeixiang investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking
AT zhangzhaokang investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking
AT huangjingjing investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking
AT yangwanhua investigatingthemolecularmechanismofquercetinprotectingagainstpodocyteinjurytoattenuatediabeticnephropathythroughnetworkpharmacologymicroarraydataanalysisandmoleculardocking