Network pharmacology study on fermented soybeans for the prevention of Alzheimer's disease in older individuals

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the disruption of synaptic communication among millions of neurons. Recent research has highlighted the potential therapeutic effectiveness of natural polyphenolic compounds in addressing AD. Soybeans are abundant in polyphenols, and their polyphenolic composition undergoes significant alteration through fermentation by Eurotium cristatum . Through comprehensive database searches, we identified active components within fermented soybean polyphenols and genes associated with AD. Subsequently, we utilized Venn diagrams to analyze the overlap between AD‐related genes and these components. Furthermore, we visualized the network between intersecting targets and proteins using Cytoscape software. The anti‐AD effects of soybeans were further explored through comprehensive analysis, including protein–protein interaction analysis, pathway enrichment analysis, and molecular docking studies. Our investigation unveiled 6‐hydroxydaidzein as a major component of fermented soybean polyphenols, shedding light on its potential therapeutic significance in combating AD. The intersection between target proteins of fermented soybeans and disease‐related targets in AD comprised 34 genes. Protein–protein interaction analysis highlighted key potential targets, including glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), glycogen synthase kinase 3 beta (GSK3B), amyloid precursor protein (APP), cyclin‐dependent kinase 5 (CDK5), and beta‐site APP cleaving enzyme 1 (BACE1). Molecular docking results demonstrated a robust binding effect between major components from fermented soybeans and the aforesaid key targets implicated in AD treatment. These findings suggest that fermented soybeans demonstrate a degree of efficacy and present promising prospects in the prevention of AD.