Cognitive benefits of fermented soybeans (Japanese natto) and its derived peptides

Abstract: Soybean and its products have been accepted as healthy foods due to their rich nutritional values. Natto is a traditional Japanese fermented soybean food that possesses beneficial health-promoting properties besides basic nutrition. The purpose of this study was to investigate the effects of fermented soybeans (Japanese natto) on cognitive function in mice and their potential mechanisms. In the scopolamine-induced memory impairment model, the most significant improvement of cognitive function was observed in the mice fed with the natto fermented for 18 h by Bacillus subtilis var. natto TTCC12, which was used in the following experiments. The oral administration of natto to senescence-accelerated mouse prone 8 (SAMP8) for 14 weeks improved memory and learning ability, compared with control and boiled soybean-fed groups. The upregulation of brain-derived neurotrophic factor (BDNF) and major postsynaptic scaffold protein, postsynaptic density protein 95 (PSD-95), was observed in the hippocampus of the natto-fed group. On the other hand, natto administration increased the phosphorylation of the NMDA receptor, Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and its downstream target, cAMP response element binding (CREB), in the hippocampus of the mice. Furthermore, the oral administration of peptides isolated from the natto for 20 days suppressed scopolamine-induced memory impairment and significantly upregulated hippocampal BDNF expression. These results demonstrated that natto and its derived peptides prevented cognitive impairment in mice, and the underlying mechanism might be closely related to regulating the hippocampal calcium and p-CREB-dependent induction of BDNF expression, possibly via activation of synaptic NMDA receptor. Our findings suggest that natto-derived peptides might be the potential to prevent age-related cognitive decline and dementia.