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

Shobako, Maiko Shobako, Naohisa Zhang, Biyun Kaneko, Kentaro Ohinata, Kousaku 京都大学 DOI:10.1038/s41598-023-30021-3

2023.02.18

概要

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.

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Acknowledgements

This work was financially supported by Sunstar Inc. This study was also supported in part by JSPS KAKENHI

Grant (KO/No. 22H02286). We performed a collaborative research to reveal the bioactivity related to the rice

bran protein digest.

Author contributions

K.O. supervised and designed the experiments; M.S., N.S. and B.Z. with help from K.K. performed the experiments and analyzed the data; M.S. and K.O. wrote the paper; and all authors discussed the results and the

manuscript.

Funding

The authors received financially support from SUNSTAR Inc.

Competing interests The authors declare no competing interests.

Additional information

Supplementary Information The online version contains supplementary material available at https://​doi.​org/​

10.​1038/​s41598-​023-​30021-3.

Correspondence and requests for materials should be addressed to K.O.

Reprints and permissions information is available at www.nature.com/reprints.

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