Long-term consumption of phytochemicals has been associated with a decreased risk of dementia. The modes of action of two flavonols (morin and isoquercitrin) and two flavanones (hesperidin and neohesperidin) were characterized as single-compound drugs in several Alzheimer's disease (AD)-related assays. First， these phytochemicals were assayed in an amyloid toxicity model (MC65 cells). Second， we examined the activity of the flavonoids in cell-free assays against β- and γ-secretases and acetylcholinesterase activities， as well as agents able to modify the fibrillogenesis of the amyloid β-peptide. Additionally， they were assayed against glutamate-induced oxytosis， as scavengers of reactive oxygen spe... More
Long-term consumption of phytochemicals has been associated with a decreased risk of dementia. The modes of action of two flavonols (morin and isoquercitrin) and two flavanones (hesperidin and neohesperidin) were characterized as single-compound drugs in several Alzheimer's disease (AD)-related assays. First， these phytochemicals were assayed in an amyloid toxicity model (MC65 cells). Second， we examined the activity of the flavonoids in cell-free assays against β- and γ-secretases and acetylcholinesterase activities， as well as agents able to modify the fibrillogenesis of the amyloid β-peptide. Additionally， they were assayed against glutamate-induced oxytosis， as scavengers of reactive oxygen species (ROS)， as inhibitors of caspase-3， -8 and -9 activation and as modulators of the chymotrypsin-like activity of the ubiquitin-proteasome system. Morin and isoquercitrin， unlike flavanones， exhibited significant activities as β- and γ-secretase inhibitors， as well as capacity to inhibit Aβ aggregation and favor its disaggregation. Flavonols and flavanones showed ROS scavenger activity (P < 0.05)， attenuation of caspase-3 and -9 activation (P < 0.05) and restoration of the reduced chymotrypsin-like activity of proteasome 20S (P < 0.05) upon HO exposure of APPswe cells. Flavanones failed to protect against glutamate-induced oxytosis. These findings provide new insight into the anti-amyloidogenic effects of morin and isoquercitrin.
