ABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aß leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aß levels and inhibiting Aß-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown. METHOD: The effects of fruitless wolfberry-sprout extract (FWE) on Aß fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aß oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aß40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aß burden and gliosis was evaluated by immunostaining and immunoblotting, respectively. RESULTS: FWE significantly inhibited Aß fibrillation and disaggregated the formed Aß fibrils, lowered Aß oligomer level and Aß-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aß burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice. CONCLUSION: These findings indicate that FWE is a promising natural agent for AD treatment.