Polyphenols and Neurodegenerative Diseases: Knowledge-Mining Insights, Mechanistic Evidence, and Emerging Nutritional Applications.

Abstract

Polyphenols are a diverse group of plant-derived bioactives that have been investigated as multi-target candidates for the potential prevention and management of neurodegenerative diseases (NDDs). We conducted an integrated bibliometric and mechanistic scoping review covering 12 polyphenol classes and seven major NDDs using records from PubMed, Embase, the Cochrane Library, and Web of Science (1940-2024). Research landscapes and emerging themes were mapped using keyword co-occurrence, clustering analyses, and BERTopic modeling. Mechanistic evidence was synthesized across core pathways, including oxidative stress, neuroinflammation, proteostasis (amyloid/tau and α-synuclein), mitochondrial dysfunction, and cholinergic modulation, to link preclinical findings with clinical outcomes. Publication output increased markedly after 2000, with China and the United States contributing the most records. Four persistent hotspots were identified: (1) antioxidant and neuroprotective effects (e.g., resveratrol, curcumin); (2) anti-inflammatory activity and intracellular signaling; (3) cognition, aging, and sex-specific responses in clinical research; and (4) animal models of memory impairment. Clinically investigated interventions include epigallocatechin gallate, Ginkgo biloba extracts, olive/cocoa polyphenols, and flavonoid-rich mixtures; however, limited bioavailability and heterogeneous trial designs constrain the strength of effect estimates. Advances in delivery systems, computational screening, and precision nutrition may improve translation. Overall, polyphenols show multi-target neuroprotective potential, but larger and more standardized clinical trials are needed to support evidence-based nutritional strategies for NDD prevention and management.