Multifunctional Roles of Natural Aaptodine in Alzheimer’s Disease: Insights from DFT and MD Studies

-induced neurotoxicity linked to Aβ in AD. Additionally, analyses using MM/PBSA and the accelerated weight histogram (AWH) methods reveal that aaptodine A exhibits a strong binding affinity to Aβ42 fibril structures. Its binding affinities are comparable to those of curcumin, a well-known compound recognized for its ability to inhibit the formation of Aβ fibrils and oligomers. The AWH results with tetramer indicate that aaptodine A binds to both toxic oligomeric species and the mature fibril. As a result, aaptodine A exhibits potential antioxidant activity through a secondary mechanism and may serve as a promising candidate for inhibiting toxic Aβ aggregates associated with AD.