Ovomemolins: Egg-derived peptides that improved cognitive decline after oral administration in mice

Eggs not only contain all the molecules necessary to nurture new life but are also rich in nutrients such as high-quality protein. For example, epidemiologic studies have shown that egg intake is positively correlated with cognitive function. Thus, we specifically examined the effect of ovalbumin, a major protein present in egg whites, on cognitive function. First, we found that an orally administered enzymatic digest of ovalbumin improves cognitive function in mice fed a high-fat diet. Then, we narrowed down candidate peptides based on the prediction of peptide production according to enzyme-substrate specificity and comprehensive peptide analysis of the digest. We found that three peptides, namely ILPEY, LYRGGLEP, and ILELP, improve cognitive function after oral administration. We also showed that ILPEY, LYRGGLEP, and ILELP were present in the digest and named them ovomemolins A (OMA), B, and C, respectively. Notably, ovomemolins are the first peptides derived from egg whites that have been shown to improve cognitive function. The cognitive improvement induced by OMA, the most abundant of the peptides in the digest, was inhibited by methyllycaconitine, an antagonist of α7nAChR, which is known to be related to memory. These results suggest that OMA improves cognitive function through the acetylcholine system. After OMA administration, brain-derived neurotrophic factor (BDNF) mRNA expression and the number of 5-bromo-2′-deoxyuridine-positive cells suggested that OMA increases hippocampal BDNF expression and neurogenesis.