Abstract
BACKGROUND: Alzheimer's disease (AD) pathogenesis is complex. The pathophysiology is not fully understood, and safe and effective treatments are needed. Glycogen synthase kinase 3β (GSK-3β) mediates AD progression through several signaling pathways. Recently, several studies have found that various natural compounds from herbs and nutraceuticals can significantly improve AD symptoms. AIMS: This review aims to provide a comprehensive summary of the potential neuroprotective impacts of natural compounds as inhibitors of GSK-3β in the treatment of AD. MATERIALS AND METHODS: We conducted a systematic literature search on PubMed, ScienceDirect, Web of Science, and Google Scholar, focusing on in vitro and in vivo studies that investigated natural compounds as inhibitors of GSK-3β in the treatment of AD. RESULTS: The mechanism may be related to GSK-3β activation inhibition to regulate amyloid beta production, tau protein hyperphosphorylation, cell apoptosis, and cellular inflammation. By reviewing recent studies on GSK-3β inhibition in phytochemicals and AD intervention, flavonoids including oxyphylla A, quercetin, morin, icariin, linarin, genipin, and isoorientin were reported as potent GSK-3β inhibitors for AD treatment. Polyphenols such as schisandrin B, magnolol, and dieckol have inhibitory effects on GSK-3β in AD models, including in vivo models. Sulforaphene, ginsenoside Rd, gypenoside XVII, falcarindiol, epibrassinolides, 1,8-Cineole, and andrographolide are promising GSK-3β inhibitors. CONCLUSIONS: Natural compounds from herbs and nutraceuticals are potential candidates for AD treatment. They may qualify as derivatives for development as promising compounds that provide enhanced pharmacological characteristics.