Identification and Screening of Potential Bioactive Peptides with Sleep-Enhancing Effects in Bovine Milk Casein Hydrolysate

作者：Qian, Jingjing; Zheng, Lin^*; Su, Guowan; Huang, Mingtao; Luo, Donghui; Zhao, Mouming^*

来源：Journal of Agricultural and Food Chemistry, 2021, 69(38): 11246-11258.

DOI：10.1021/acs.jafc.1c03937

• casein tryptic hydrolysate
• sleep
• peptidomics
• virtual screening
• GABA(A) receptor

Casein tryptic hydrolysate (CTH) has been proven to possess stress-relieving and sleep-enhancing effects, but only one decapeptide YLGYLEQLLR (a-CZP) in CTH was reported to exhibit affinity for the benzodiazepine site of a GABA(A) receptor (GABA(A)R). This study aimed to compare the sleep-enhancing effects between CTH and alpha-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 alpha-CZP. The alpha-CZP in CTH was degraded more slowly than the synthetic alpha-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 GABA(A)R 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.