Phytotherapeutic approaches are of immense value in the treatment of advanced Alzheimer's disease (AD) because of their diverse biological components and potential multitarget mechanisms. In this study, quercetin, a natural neuroprotective flavonoid, was encapsulated in human serum albumin to obtain HSA@QC nanoparticles (HQ NPs) as a natural phyto-antioxidant albumin nanoagent for the treatment of advanced AD. HQ NPs showed excellent antioxidant effects and protected PC12 cells from H2O2-induced oxidative damage. The intranasal administration of HQ NPs in 11-month-old APP/PS1 mice, which represented advanced AD, effectively prevented the loss of body weight, increased survival rates, and significantly reduced oxidative stress, Aβ aggregation, neuronal apoptosis, and synaptic damage in the brain. It also ultimately reversed severely impaired cognitive function. In addition to their favorable anti-AD effects, HQ NPs exhibited excellent biosafety and biocompatibility owing to their natural composition and are expected to become an ideal choice for future drug development and clinical applications.
Keywords: Advanced Alzheimer’s disease; antioxidant; intranasal administration; phytotherapeutic strategy; quercetin.