A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration
Abstract The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administrat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-44161-z |
| _version_ | 1797452868941250560 |
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| author | Lihong Cheng Mitsuru Tanaka Atsuko Yoshino Yuki Nagasato Fuyuko Takata Shinya Dohgu Toshiro Matsui |
| author_facet | Lihong Cheng Mitsuru Tanaka Atsuko Yoshino Yuki Nagasato Fuyuko Takata Shinya Dohgu Toshiro Matsui |
| author_sort | Lihong Cheng |
| collection | DOAJ |
| description | Abstract The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration. Stable isotope-labeled Tyr-Pro (Tyr-[13C5,15N]Pro) was orally administered to male ICR mice at 10 or 100 mg/kg. Surprisingly, the intact labeled Tyr-Pro exhibited maximal plasma and brain levels 15 min after administration (plasma: area under the curve [AUC 0–120 min], 1331 ± 267 pmol·min/mL-plasma; brain: AUC 0–120 min of 0.34 ± 0.11 pmol·min/mg-dry brain, at 10 mg/kg). In addition, we detected labeled Tyr-Pro in the brain parenchyma, indicating a validated blood–brain-barrier (BBB) transportability. Moreover, we confirmed the preferable accumulation of Tyr-Pro in the hypothalamus, hippocampus, and cortex with > 0.02 pmol/mg-tissue. In conclusion, we provided the first evidence that orally administered Tyr-Pro at 10 mg/kg directly entered the blood circulation with an absorption ratio of 0.15%, of which 2.5% of Tyr-Pro was transported from the plasma to the mouse brain parenchyma. |
| first_indexed | 2024-03-09T15:14:52Z |
| format | Article |
| id | doaj.art-ae70594590924614a53de899ae1215ed |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:14:52Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ae70594590924614a53de899ae1215ed2023-11-26T13:08:47ZengNature PortfolioScientific Reports2045-23222023-10-0113111110.1038/s41598-023-44161-zA memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administrationLihong Cheng0Mitsuru Tanaka1Atsuko Yoshino2Yuki Nagasato3Fuyuko Takata4Shinya Dohgu5Toshiro Matsui6Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu UniversityDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka UniversityDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu UniversityAbstract The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration. Stable isotope-labeled Tyr-Pro (Tyr-[13C5,15N]Pro) was orally administered to male ICR mice at 10 or 100 mg/kg. Surprisingly, the intact labeled Tyr-Pro exhibited maximal plasma and brain levels 15 min after administration (plasma: area under the curve [AUC 0–120 min], 1331 ± 267 pmol·min/mL-plasma; brain: AUC 0–120 min of 0.34 ± 0.11 pmol·min/mg-dry brain, at 10 mg/kg). In addition, we detected labeled Tyr-Pro in the brain parenchyma, indicating a validated blood–brain-barrier (BBB) transportability. Moreover, we confirmed the preferable accumulation of Tyr-Pro in the hypothalamus, hippocampus, and cortex with > 0.02 pmol/mg-tissue. In conclusion, we provided the first evidence that orally administered Tyr-Pro at 10 mg/kg directly entered the blood circulation with an absorption ratio of 0.15%, of which 2.5% of Tyr-Pro was transported from the plasma to the mouse brain parenchyma.https://doi.org/10.1038/s41598-023-44161-z |
| spellingShingle | Lihong Cheng Mitsuru Tanaka Atsuko Yoshino Yuki Nagasato Fuyuko Takata Shinya Dohgu Toshiro Matsui A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration Scientific Reports |
| title | A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration |
| title_full | A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration |
| title_fullStr | A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration |
| title_full_unstemmed | A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration |
| title_short | A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration |
| title_sort | memory improving dipeptide tyr pro can reach the mouse brain after oral administration |
| url | https://doi.org/10.1038/s41598-023-44161-z |
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