Ginkgo Biloba-Derived Flavonoids as Metal Chelators in Alzheimer’s Neurochemistry: A Biochemical Approach

Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder marked by the pathological accumulation of amyloid-β plaques, neurofibrillary tangles due to tau hyperphosphorylation, and a profound imbalance in metal ion homeostasis. Increasing evidence suggests that transition metals such as iron (Fe), copper (Cu), and zinc (Zn) contribute to the pathogenesis of AD by catalyzing the production of reactive oxygen species (ROS) through redox cycling, thus exacerbating oxidative stress and protein misfolding. Chelation of these metals is emerging as a viable therapeutic strategy to mitigate these effects. This study investigates flavonoids extracted from Ginkgo biloba—specifically quercetin, kaempferol, and isorhamnetin—as natural, multifunctional agents capable of chelating redox-active metals and scavenging free radicals. Using a comprehensive biochemical approach, we examined their molecular structures, binding mechanisms, and pharmacological efficacy through spectrophotometric assays, antioxidant capacity analyses, and molecular docking simulations. Our findings reveal that these flavonoids exhibit significant Fe(II) and Cu(II) chelation ability, inhibit amyloid aggregation, and demonstrate potent antioxidant activity. Quercetin, in particular, displayed the highest metal binding affinity and radical scavenging potential. By modulating metal ion levels and preventing oxidative damage, Ginkgo biloba- derived flavonoids represent promising neuroprotective candidates in AD treatment. This article offers mechanistic insights into their biochemical behavior, emphasizing their relevance in the development of multi-targeted interventions for Alzheimer’s disease.