Arbutin in Alzheimer’s disease: A network-based approach to uncover drug targets through molecular mapping

Abstract

Alzheimer’s disease (AD), a leading cause of dementia, is characterized by progressive neurodegeneration and cognitive decline. Current treatments, including cholinesterase and N-methyl-D-aspartate (NMDA) inhibitors, provide symptomatic relief but are often associated with adverse effects. This has driven interest in natural compounds like arbutin, an endogenous molecule, for their therapeutic potential in AD. This study employs a network pharmacology approach to explore arbutin’s molecular mechanisms and pathways. Arbutin targets were retrieved from SwissTargetPrediction and PharmMapper, while AD-related targets were obtained from DisGeNET and GeneCards. After merging and removing duplicates, 37 common targets were identified. Gene ontology and KEGG enrichment analyses, performed using ShinyGO, revealed key biological processes associated with AD, including phosphorus metabolic regulation, cell proliferation, apoptosis, oxidative response, and abiotic stress. Among the top five biological processes, nine out of ten hub genes were enriched. KEGG analysis highlighted ten significant pathways, with AD and cancer being the most predominant based on gene count. The Maximal Clique Centrality method in the CytoHubba plugin of Cytoscape identified the top ten hub genes. Molecular docking studies using PyRx and Discovery Studio revealed that AKT-1 exhibited the highest binding affinity with arbutin (-7.2 kcal/mol). These findings suggest that arbutin plays a crucial role in modulating key pathways associated with AD, offering potential therapeutic benefits. Targeting these pathways could reduce AD progression, highlighting arbutin as a promising candidate for further drug development.