Wu_2025_Molecules_30_

Alzheimer's disease (AD) is characterized by cholinergic deficits and neuronal damage, making acetylcholinesterase (AChE) a crucial therapeutic target. Cyanidin derivatives, sourced from the diet as anthocyanins, exhibit neuroprotective properties, yet comparative investigations are scarce. This research explored the neuroprotective impacts of five cyanidin derivatives, namely cyanidin-3-O-(trans-p-coumaroyl)-diglycoside (C3GG), cyanidin-3-O-rutinoside (C3R), cyanidin-3-O-arabinoside (C3A), cyanidin-3-O-sophoroside (C3S), and cyanidin-3-O-xyloside (C3X), utilizing an aluminum-chloride (AlCl(3))-induced zebrafish model of AD. The administration of these compounds ameliorated zebrafish locomotor impairments, suppressed AChE activity, decreased brain oxidative stress levels, upregulated AD-related gene expression, and mitigated brain tissue pathological changes. Molecular docking and dynamics simulations indicated that cyanidin derivatives exhibit robust binding affinity and stable binding to AChE. Particularly, C3R demonstrated the most potent multi-faceted neuroprotective effects among the tested derivatives, suggesting its potential as a promising lead compound for AD therapy.