Rice-memolin, a novel peptide derived from rice bran, improves cognitive function after oral administration in mice

Abstract

Many people eat polished rice, while rice bran, a by-product known to be rich in protein and expected to have potential functions for health benefits, has not been effectively utilized. In this study, we determined that orally administered Val-Tyr-Thr-Pro-Gly (VYTPG) derived from rice bran protein improved cognitive decline in mice fed a high-fat diet (HFD). It was demonstrated that VYTPG was released from model peptides corresponding to fragment sequences of original rice proteins (Os01g0941500, Os01g0872700, and allergenic protein) after treatment with thermolysin, a microorganism-derived enzyme often used in industrial scale processes. The thermolysin digest also improved cognitive decline after oral administration in mice. Because VYTPG (1.0 mg/kg) potently improved cognitive decline and is enzymatically produced from the rice bran, we named it rice-memolin. Next, we investigated the mechanisms underlying the cognitive decline improvement associated with rice-memolin. Methyllycaconitine, an antagonist for α7 nicotinic acetylcholine receptor, suppressed the rice-memolin-induced effect, suggesting that rice-memolin improved cognitive decline coupled to the acetylcholine system. Rice-memolin increased the number of 5-bromo-2’-deoxyuridine (BrdU)-positive cells and promoted the mRNA expression of EGF and FGF-2 in the hippocampus, implying that these neurotropic factors play a role in hippocampal neurogenesis after rice-memolin administration. Epidemiologic studies demonstrated that diabetes is a risk factor for dementia; therefore, we also examined the effect of rice-memolin on glucose metabolism. Rice-memolin improved glucose intolerance. In conclusion, we identified a novel rice-derived peptide that can improve cognitive decline. The mechanisms are associated with acetylcholine and hippocampal neurogenesis. Rice-memolin is the first rice-brain-derived peptide able to improve cognitive decline.

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

“…It has been reported that diabetic patients are 1.7 times more susceptible to dementia than the control group 2 . Furthermore, we revealed that a high‐fat diet (HFD) induces glucose metabolism impairment and cognitive decline in mice 3,4 . Considering that milk intake is a protective factor, we found that tripeptide derived from α casein, a major component in bovine milk, ameliorated cognitive decline induced by HFD intake 3 .…”

“…We previously reported that milk‐derived YLG used to improve cognitive decline induced by HFD intake increased insulin sensitivity in the ITT 3 . VYTPG, named rice‐memolin, also improved glucose metabolism after oral administration 4 . In contrast, OMA improved cognitive function but did not affect blood glucose levels in the OGTT and ITT (Figure S4).…”

“…The glucose‐lowering effect was assessed using the oral glucose tolerance test (OGTT). The OGTT was performed as described previously 3,4,14 . Briefly, glucose solution was administered orally at a dose of 2 g/kg to mice fasted for 18 h on Day 7.…”

“…Herein, 10‐ to 11‐week‐old male ddY mice were purchased from SLC (Shizuoka, Japan). All mice were kept as previously described, 3 , 4 with slight modification. Rearing conditions of mice were established as follows: 23 ± 1°C on a 12‐h light–dark cycle with lights on at 7 a.m. Each mouse was acclimatized using a standard rodent diet, MF (Oriental Yeast, Osaka, Japan), for more than 6 days.…”

“…2 Furthermore, we revealed that a high-fat diet (HFD) induces glucose metabolism impairment and cognitive decline in mice. 3,4 Considering that milk intake is a protective factor, we found that tripeptide derived from α casein, a major component in bovine milk, ameliorated cognitive decline induced by HFD intake. 3 The discovery of peptides derived from dairy protein sources that improve cognitive function may provide new measures of preventing cognitive decline, including mild cognitive impairment and dementia.…”