A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration
Lihong Cheng, Mitsuru Tanaka, Atsuko Yoshino, Yuki Nagasato, Fuyuko Takata, Shinya Dohgu, Toshiro Matsui
Abstract
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-[ 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.