Mulberry fruit extract alleviates the intracellular amyloid-β oligomer-induced cognitive disturbance and oxidative stress in Alzheimer's disease model mice

Intracellular amyloid-beta (A beta) oligomers are key therapeutic targets because they are strongly cytotoxic and play crucial roles in the cognitive function in Alzheimer's disease (AD). Anthocyanins, polyphenolic flavonoids with antioxidant and neuroprotective properties, are potential therapeutic candidates for AD. Here, we investigated the effects of anthocyanin-enriched extracts from fruits of mulberry (Morus alba Linn.) in Thailand against the neurotoxicity of A beta oligomers. Using the monitoring system for A beta aggregation, we showed that the extract induced the dissociation of A beta in cultured HEK293T cells. To investigate the effects on cognitive function, we orally administered the extract to A beta-GFP transgenic mice (A beta-GFP Tg), a mouse model that expresses A beta oligomers inside neurons, and performed the novel object recognition test and passive avoidance test. A beta-GFP Tg usually showed deficits in novel object recognition memory and reference memory compared with non-Tg, but administration of the extract improved both compared with vehicle-treated A beta-GFP Tg. A beta-GFP Tg exhibited lower superoxide dismutase (SOD) activity than non-Tg. However, after the administration of the extract, the SOD activity was restored. These results suggest that Thai mulberry fruit extract ameliorates cytotoxicity induced by the intracellular A beta oligomers and may be an effective therapeutic or preventive candidate for AD.

Automated summary

Intracellular amyloid-beta (A beta) oligomers are toxic and play crucial roles in Alzheimer's disease (AD). Anthocyanins, with antioxidant and neuroprotective properties, are being investigated as potential therapeutic candidates for AD. Extracts from Thai mulberry fruit have shown to ameliorate cytotoxicity induced by intracellular A beta oligomers and could be an effective therapeutic or preventive candidate for AD.