Anti-cognitive impairment effects of dipeptide detected in blood after orally administered natto

Natto is a traditional Japanese fermented soybean food with beneficial health-promoting properties besides basic nutrition. We have reported that long-term intake of natto suppresses the decline in cognitive function in a mouse model of accelerated aging (SAMP8); however, its active compounds and molecular mechanism are still unclear. In this study, we identified the bioactive peptides with cognition-enhancing potential in anti-cognitive impairment effects in mice model of scopolamine-induced amnesia.

Peptide extracts (100 mg/kg) prepared from fermented natto for 18 h and 42 h by Bacillus subtilis var. natto TTCC12 were orally administered to Wistar rats by gavage. After 1 h, the blood plasma samples were collected and subjected to metabolomic analysis. Some dipeptides were increased by the oral administration of the peptide extract prepared from 18 h-fermented natto but not increased by that of 42 h-fermented natto. Among them, we investigated the ameliorating effects of Ala-Tyr (AY), Gln-Gln (QQ), and Ser-Arg (SR) against scopolamine-induced cognitive impairment. AY and QQ improved learning and memory in both the novel object recognition test and the passive avoidance test. Particularly, the treatment of QQ increased in a dose-dependent manner, and a statistically significant difference was found in the group that received a 3 mg/kg dose of QQ. Furthermore, QQ increased the expression of choline acetyltransferase (ChAT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. These results suggest that QQ possesses the potential to act as a neuroprotective agent against cognitive impairment.