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

Abstract

Intracellular amyloid-β (Aβ) 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 Aβ oligomers. Using the monitoring system for Aβ aggregation, we showed that the extract induced the dissociation of Aβ in cultured HEK293T cells. To investigate the effects on cognitive function, we orally administered the extract to Aβ-GFP transgenic mice (Aβ-GFP Tg), a mouse model that expresses Aβ oligomers inside neurons, and performed the novel object recognition test and passive avoidance test. Aβ-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 Aβ-GFP Tg. Aβ-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 Aβ oligomers and may be an effective therapeutic or preventive candidate for AD.

Keywords: Alzheimer's disease; amyloid β-protein; anthocyanin; cognitive function; mulberry fruit extract; oligomer.