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

• Published in: Scientific reports Vol. 11; no. 1; p. 22959
• Main Authors: Zu, Guoxiu, Sun, Keyun, Li, Ling, Zu, Xiuli, Han, Tao, Huang, Hailiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/449; 692/163; 692/308; AKT1 protein; Alzheimer Disease - drug therapy; Alzheimer's disease; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Drug Delivery Systems; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Genomes; Heredity; Humanities and Social Sciences; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Inflammation; MAP kinase; Medicine, Chinese Traditional; Molecular Docking Simulation; Molecular dynamics; multidisciplinary; Neurodegenerative diseases; Protein Interaction Maps; Proteins; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Science; Science (multidisciplinary); Signal transduction; Therapeutic applications; Therapeutic targets; Tumor necrosis factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02248-5

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.