Novel soy peptides that improve cognitive function after oral administration

Background and objective: Healthy aging is important for the increasing elderly population worldwide. We found that the enzymatic digest of soy β-conglycinin administered orally improves cognitive decline in mice. We then searched for peptides present in the digest that can improve cognitive function. Methods: Cognitive function was evaluated by behavior tests, such as the novel object recognition test (ORT) and the object location test (OLT), using male mice. We investigated whether orally administered samples improved cognitive decline in mice that were treated with high fat diet (HFD) for one week [1]. The candidate peptides were synthesized by Fmoc strategy and purified by reverse phase HPLC. Results: Based on the comprehensive analysis information of the digest [2] and homology with known peptides that improve cognitive decline, candidate peptides were chemosynthesized. Among them, we found one decapeptide and one dodecapeptide increased the approach time to the new object after oral administration in mice fed with HFD diet. Thus, we found that these peptides improved cognitive decline induced by HFD intake in the ORT. In the OLT, we also found that they improved cognitive decline. Thus, we demonstrated that the peptides were effective in improving cognitive decline by using different two paradigms. Acetylcholine (ACh) is known to be a neurotransmitter that plays a critical role in cognitive function. To investigate the involvement of the acetylcholine system, methyllycaconitine (MLA), an antagonist specific for the a7 nicotinic ACh receptor (a7nAChR), was used. Both the soy β-conglycinin digest and the synthetic peptide improved cognitive decline induced by HFD intake, and these improvements were blocked by MLA. These results suggest that the improvements were associated with the a7nAChR system. Conclusion: we found novel soy protein-derived peptides improving cognitive decline and the effect of peptide is coupled to the acetylcholine system.