Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

Abstract Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using t...

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Autores principales:	Guoxiu Zu, Keyun Sun, Ling Li, Xiuli Zu, Tao Han, Hailiang Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42e9e9d04f7448a0aeccc4e2338bc236
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spelling	oai:doaj.org-article:42e9e9d04f7448a0aeccc4e2338bc2362021-11-28T12:16:38ZMechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus10.1038/s41598-021-02248-52045-2322https://doaj.org/article/42e9e9d04f7448a0aeccc4e2338bc2362021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02248-5https://doaj.org/toc/2045-2322Abstract Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.Guoxiu ZuKeyun SunLing LiXiuli ZuTao HanHailiang HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guoxiu Zu Keyun Sun Ling Li Xiuli Zu Tao Han Hailiang Huang Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
description	Abstract Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.
format	article
author	Guoxiu Zu Keyun Sun Ling Li Xiuli Zu Tao Han Hailiang Huang
author_facet	Guoxiu Zu Keyun Sun Ling Li Xiuli Zu Tao Han Hailiang Huang
author_sort	Guoxiu Zu
title	Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
title_short	Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
title_full	Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
title_fullStr	Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
title_full_unstemmed	Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
title_sort	mechanism of quercetin therapeutic targets for alzheimer disease and type 2 diabetes mellitus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/42e9e9d04f7448a0aeccc4e2338bc236
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Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

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