School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou 510650, China.
J Agric Food Chem. 2021 Sep 29;69(38):11246-11258. doi: 10.1021/acs.jafc.1c03937. Epub 2021 Sep 20.
Casein tryptic hydrolysate (CTH) has been proven to possess stress-relieving and sleep-enhancing effects, but only one decapeptide YLGYLEQLLR (α-CZP) in CTH was reported to exhibit affinity for the benzodiazepine site of a GABA receptor (GABAR). This study aimed to compare the sleep-enhancing effects between CTH and α-CZP and to explore novel sleep-enhancing peptides. Our results showed that CTH significantly prolonged sleep duration in mice, which was almost 2-fold longer than that of α-CZP. The α-CZP in CTH was degraded more slowly than the synthetic α-CZP; meanwhile, CTH could release other potential sleep-enhancing peptides during gastrointestinal digestion. Additionally, two peptides YPVEPF and YFYPEL with strong sleep-enhancing activity were explored by virtual screening. Especially, YPVEPF could significantly prolong the sleep duration from 559.00 ± 272.24 to 2501.63 ± 1021.21 s and increase the sleep rate from 58.33 to 83.33% in mice. Moreover, YPVEPF and YFYPEL could bind with the Ser-205 and Phe-77 residues of GABAR via hydrogen bonds and lipid contacts. They were largely released after digestion with 11.19 ± 0.15 and 1.78 ± 0.01 g/kg, respectively.
酪蛋白胰酶水解物（CTH）已被证明具有缓解压力和改善睡眠的作用，但只有 CTH 中的一种十肽 YLGYLEQLLR（α-CZP）被报道对 GABA 受体（GABAR）的苯二氮䓬位点具有亲和力。本研究旨在比较 CTH 和 α-CZP 的改善睡眠作用，并探索新的改善睡眠肽。我们的结果表明，CTH 可显著延长小鼠的睡眠时间，几乎是 α-CZP 的 2 倍。CTH 中的 α-CZP 比合成的 α-CZP 降解得更慢；同时，CTH 可以在胃肠道消化过程中释放其他潜在的改善睡眠肽。此外，通过虚拟筛选探索了两种具有强改善睡眠活性的肽 YPVEPF 和 YFYPEL。特别是，YPVEPF 可显著延长小鼠的睡眠时间，从 559.00 ± 272.24 秒延长至 2501.63 ± 1021.21 秒，睡眠率从 58.33%增加至 83.33%。此外，YPVEPF 和 YFYPEL 可以通过氢键和脂接触与 GABAR 的 Ser-205 和 Phe-77 残基结合。它们在分别以 1.19 ± 0.15 g/kg 和 1.78 ± 0.01 g/kg 进行消化后，大量释放。
