Naturally occurring biflavonoids with amyloid β aggregation inhibitory activity for development of anti-Alzheimer agents

Abstract Amyloid β (Aβ) aggregation plays an essential role in promoting the progression of Alzheimer’s disease (AD). Therefore, the inhibition of Aβ aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aβ 40 aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone ( 1 ) and its monomethoxy derivatives ( 2 , 3 , and 5 ) exhibited the most potent inhibitory activity, with IC 50 values of approximately 5 μM. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.