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

  • Jingjing Qian
    Jingjing Qian
    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
  • Lin Zheng*
    Lin Zheng
    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
    *Email: [email protected]. Tel/Fax: +86 20 87113914.
    More by Lin Zheng
  • Guowan Su
    Guowan Su
    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
    More by Guowan Su
  • Mingtao Huang
    Mingtao Huang
    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
  • Donghui Luo
    Donghui Luo
    Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521000, China
    More by Donghui Luo
  • , and 
  • Mouming Zhao*
    Mouming Zhao
    School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
    Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521000, China
    Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou 510650, China
    *Email: [email protected]. Tel/Fax: +86 20 87113914.
    More by Mouming Zhao
Cite this: J. Agric. Food Chem. 2021, 69, 38, 11246–11258
Publication Date (Web):September 20, 2021
https://doi.org/10.1021/acs.jafc.1c03937
Copyright © 2021 American Chemical Society

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    Abstract

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    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 GABAA receptor (GABAAR). 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 GABAAR 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.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jafc.1c03937.

    • (Figure S1) Chemical structures of α-CZP, YPVEPF, YFYPEL, and YYVPL; (Figure S2) MS/MS spectrum of α-CZP and its fragments; (Table S1) identification of peptide profiles of casein tryptic hydrolysate; (Table S2) identification of peptide profiles of casein tryptic hydrolysate after 240 min digestion; and (Table S3) results of virtual screening for 131 peptides with GABAAR (PDF)

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    Cited By

    This article is cited by 12 publications.

    1. Xiangxin Wang, Dongying Cui, Xueyin Qu, Hong You, Fan Lei, Jianqiao Li, Yang Xie, Haoshu Zhang, Yongjiu Zhang, Shilong Jiang, Qinggang Xie. Analytical Ultracentrifugation-Calibrated Anion-Exchange Chromatography for Sensitive and Intact Determination of Osteopontin in Infant Formula and Dairy Products. Journal of Agricultural and Food Chemistry 2023, 71 (37) , 13880-13888. https://doi.org/10.1021/acs.jafc.3c03589
    2. Minzhi Zhou, Tianyuan Song, Wen Li, Mingtao Huang, Lin Zheng, Mouming Zhao. Identification and Screening of Potential ACE2 Activating Peptides from Soybean Protein Isolate Hydrolysate against Ang II-Induced Endothelial Dysfunction. Journal of Agricultural and Food Chemistry 2023, 71 (31) , 11957-11969. https://doi.org/10.1021/acs.jafc.3c03013
    3. Jingjing Qian, Lin Zheng, Yijun Zhao, Mouming Zhao. Stability, Bioavailability, and Structure–Activity Relationship of Casein-Derived Peptide YPVEPF with a Sleep-Enhancing Effect. Journal of Agricultural and Food Chemistry 2022, 70 (47) , 14947-14958. https://doi.org/10.1021/acs.jafc.2c05024
    4. Marie-Pierre St-Onge, Faris M. Zuraikat, Mackenzie Neilson. Exploring the Role of Dairy Products In Sleep Quality: From Population Studies to Mechanistic Evaluations. Advances in Nutrition 2023, 14 (2) , 283-294. https://doi.org/10.1016/j.advnut.2023.01.004
    5. Shuguang Wang, Mouming Zhao, Hongbing Fan, Jianping Wu. Emerging proteins as precursors of bioactive peptides/hydrolysates with health benefits. Current Opinion in Food Science 2022, 48 , 100914. https://doi.org/10.1016/j.cofs.2022.100914
    6. Qiongyao Xu, Lin Zheng, Mingtao Huang, Mouming Zhao. Exploring structural features of potent dipeptidyl peptidase IV (DPP-IV) inhibitory peptides derived from tilapia (Oreochromis niloticus) skin gelatin by an integrated approach of multivariate analysis and Gly-Pro-based peptide library. Food Chemistry 2022, 397 , 133821. https://doi.org/10.1016/j.foodchem.2022.133821
    7. Daiyao Liu, Jianming Zhang, Juan Chen, Chengcheng Zhang, Huaxi Yi, Daqun Liu. Carrot-based fermentation juice rich in sleep-promoting components improved sleep in mice. Frontiers in Nutrition 2022, 9 https://doi.org/10.3389/fnut.2022.1043055
    8. Chunyan Yu, Lin Zheng, Yongjian Cai, Qiangzhong Zhao, Mouming Zhao. Desirable characteristics of casein peptides with simultaneously enhanced emulsion forming ability and antioxidative capacity in O/W emulsion. Food Hydrocolloids 2022, 131 , 107812. https://doi.org/10.1016/j.foodhyd.2022.107812
    9. Lei Cai, Qian Tao, Wenzhi Li, Xiping Zhu, Chun Cui. The anti-anxiety/depression effect of a combined complex of casein hydrolysate and γ-aminobutyric acid on C57BL/6 mice. Frontiers in Nutrition 2022, 9 https://doi.org/10.3389/fnut.2022.971853
    10. Simon Benoit, Catherine Chaumontet, Nicolas Violle, Audrey Boulier, Zeeshan Hafeez, Céline Cakir-Kiefer, Daniel Tomé, Jessica Schwarz, Laurent Miclo. The Anxiolytic-like Properties of a Tryptic Hydrolysate of Bovine αs1 Casein Containing α-Casozepine Rely on GABAA Receptor Benzodiazepine Binding Sites but Not the Vagus Nerve. Nutrients 2022, 14 (11) , 2212. https://doi.org/10.3390/nu14112212
    11. Min Wang, William Kwame Amakye, Congcong Gong, Zhengyu Ren, Erdong Yuan, Jiaoyan Ren. Effect of oral and intraperitoneal administration of walnut-derived pentapeptide PW5 on cognitive impairments in APPSWE/PS1ΔE9 mice. Free Radical Biology and Medicine 2022, 180 , 191-197. https://doi.org/10.1016/j.freeradbiomed.2022.01.003
    12. Kokila Thiagarajah, Huei Phing Chee, Nam Weng Sit. Effect of Alpha-S1-Casein Tryptic Hydrolysate and L-Theanine on Poor Sleep Quality: A Double Blind, Randomized Placebo-Controlled Crossover Trial. Nutrients 2022, 14 (3) , 652. https://doi.org/10.3390/nu14030652

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