A memory‑improving dipeptide, Tyr‑Pro, can reach the mouse brain after oral administration

DOI IR (HANDLE) PubMed Open Access
  • Cheng, Lihong
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University
  • Tanaka, Mitsuru
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University
  • Yoshino, Atsuko
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University
  • Nagasato, Yuki
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University
  • Takata, Fuyuko
    Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University
  • Dohgu, Shinya
    Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University
  • Matsui, Toshiro
    Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University

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  • A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration

Description

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-[<13>^C_5,<15>^N]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.

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