Biflavonoids can Potentially Inhibit Amyloid Beta Internalization to Mitigate Its Cytotoxic Events.

Amyloid-β-42 (Aβ42) internalization plays a critical role in Alzheimer's disease (AD) pathology. We investigated whether biflavonoids, natural small molecules, could inhibit Aβ42 uptake and mitigate its cytotoxicity. Biochemical and imaging analyses revealed that biflavonoids dose-dependently blocked Aβ42 internalization, preventing lamin fragmentation and caspase activation which are considered as key steps in Aβ42-induced cell death. Confocal microscopy and Western blotting confirmed reduced Aβ42 entry, while aggregation assays in cell-free conditions demonstrated biflavonoids suppress Aβ42 fibril, oligomer, and β-sheet formation. These findings suggest biflavonoids exert cytoprotective effects by inhibiting both Aβ42 conformational changes and cellular uptake, positioning them as promising anti-amyloidogenic agents for AD therapy.