Mulberry Fruit Cultivar 'Chiang Mai' Prevents Beta-Amyloid Toxicity in PC12 Neuronal Cells and in a Drosophila Model of Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia, characterized by chronic neuron loss and cognitive problems. Aggregated amyloid beta (A beta) peptides, a product of cleaved amyloid precursor protein (APP) by beta-secretase 1 (BACE-1), have been indicated for the progressive pathogenesis of AD. Currently, screening for anti-AD compounds in foodstuffs is increasing, with promising results. Hence, the purpose of this study was to investigate the extraction conditions, phytochemical contents, and anti-AD properties, targeting A beta peptides of Morus cf. nigra 'Chiang Mai' (MNCM) both in vitro and in vivo. Data showed that the aqueous extract of MNCM contained high amounts of cyanidin, keracyanin, and kuromanin as anthocyanidin and anthocyanins. The extract also strongly inhibited cholinesterases and BACE-1 in vitro. Moreover, MNCM extract prevented A beta-induced neurotoxicity and promoted neurite outgrowth in neuronal cells. Interestingly, MNCM extract reduced A beta(1-42) peptides and improved locomotory coordination of Drosophila co-expressing human APP and BACE-1, specifically in the brain. These findings suggest that MNCM may be useful as an AD preventive agent by targeting A beta formation.