Ginkgo biloba Flavonoids as Nutraceuticals for Alzheimer’s: Boosting Cerebral Blood Flow via Endothelial Nitric Oxide Pathways while Inhibiting Beta-Amyloid Fibrillisation

Background: Alzheimer’s Disease (AD) involves Amyloid-Beta (Aβ) plaque accumulation, endothelial dysfunction, and cerebral hypoperfusion, with Ginkgo biloba flavonoids (e.g., quercetin, kaempferol glycosides in EGb761) emerging as nutraceuticals that enhance endothelial Nitric Oxide (NO) pathways for vasodilation while inhibiting Aβ fibrillisation. Aim: To review the dual mechanisms of Ginkgo flavonoids in boosting cerebral blood flow via endothelial Nitric Oxide Synthase (eNOS) activation and preventing Aβ aggregation, alongside their nutraceutical applications, preclinical/clinical evidence, and safety profile for AD management. Methods: Comprehensive literature synthesis from in vitro (e.g., DPPH, Thioflavin T (ThT) assays), animal models (e.g., hippocampal perfusion in AD rodents), clinical trials (e.g., EGb761 with donepezil), and network pharmacology analyses, structured around phytochemical profiles, mechanistic pathways, formulations, and future directions. Results: Flavonoids upregulate eNOS via PI3K/Akt (20-50% NO increase, 15-25% flow enhancement), scavenge Reactive Oxygen Species (ROS), inhibit arginase, and promote glymphatic clearance; They bind Aβ1-42 (Kd 1-5 μM), reduce fibril formation (40-82% ThT inhibition), downregulate Beta site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1), and suppress neuroinflammation. Clinical data show cognitive gains (+2.4 Korean Mini-Mental State Examination (K-MMSE) points) and Aβ oligomer reduction in adjunct therapy, with safe dosing (120-240 mg/day EGb761). Major Findings: Ginkgo flavonoids offer multifaceted AD benefits through NO-mediated perfusion and anti-amyloid actions, ideal for functional foods and supplements.