Integrating molecular docking and biological evaluation of metal-phytochemical complexes in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and neuronal loss. Its pathogenesis involves multiple interconnected mechanisms, including amyloid-β (Aβ) aggregation, τ hyperphosphorylation, oxidative stress, neuroinflammation, and metal ion dyshomeostasis. Current therapeutic strategies primarily provide symptomatic relief, underscoring the urgent need for multitargeted approaches. Natural products have emerged as promising candidates due to their structural diversity and ability to modulate several pathological pathways simultaneously. Among these, triterpenoid glycosides such as momordicoside L exhibit notable antioxidant and anti-inflammatory properties. Recent advances highlight the potential of metal-phytochemical complexes in enhancing pharmacological efficacy. Complexation with metals such as copper may improve the stability, bioavailability, and biological activity of phytochemicals while modulating metal-induced toxicity associated with AD. Molecular docking studies provide insights into interactions with key targets, while in vitro and in vivo investigations demonstrate improved neuroprotective effects, including enhanced cell viability, reduced inflammatory responses, and cognitive improvement. This review emphasizes the integration of analytical characterization, computational modeling, and biological validation, supporting the development of metal-natural product complexes as innovative multitarget therapeutic agents for AD.