Chronic insomnia can significantly impair cognitive function and emotional stability, and may even trigger or exacerbate systemic health issues such as cardiovascular disease and metabolic disorders. This study intended to identify novel potential sleep-promoting peptide candidates from egg proteins and elucidate their molecular mechanisms with γ-aminobutyric acid (GABA) type-A receptor (GABAAR), orexin 2 receptor (OX2R), and nociceptin/orphanin-FQ receptor (NOPR). Through in silico hydrolysis, water solubility and toxicity prediction, molecular docking, and molecular dynamics simulations, six novel potential peptide candidates were identified. Among these, QPVDNY exhibited the strongest binding affinities of –9.2, –9.7 and –9.0 kcal/mol with GABAAR, OX2R and NOPR, respectively. Subsequently, peptide LKPIAAEVY showed affinities of –8.6, –9.7 and –8.2 kcal/mol with the three receptors, respectively. Molecular docking results showed that peptides QPVDNY and LKPIAAEVY bound to residues Leu259, Thr256, His267, and Glu270 of GABAAR via π-alkyl and hydrogen bonds, formed π-alkyl bonds with residues Pro131, Cys107, Phe227, Phe346 and His350 of OX2R. In addition, these two peptides formed π-alkyl bonds and hydrogen bonds with residues Val283, Met134 and Tyr131 of NOPR, meanwhile, they bound to residue Asp130 of NOPR via hydrogen bonds and a salt bridge. Molecular dynamics simulations confirmed the good stability of the peptide-receptor complexes. This study identifies novel potential candidates for natural sleep-promoting foods and establishes an efficient approach for screening food-derived bioactive peptides.

Using a combination of molecular docking and in vitro activity evaluation, three antifreeze peptides (i.e., PQGPVGNTGPKG, LSGPTGEAGRE and GGRGPEGPAGAR) were selected from 386 tilapia skin collagen peptides, and their interactions with ice crystals were explored. The thermal hysteresis activities of these peptides were 1.57, 1.82, and 1.22 ℃, respectively. After freeze-thaw cycles, catalase retained 57.0%, 66.7%, and 52.3% of its initial activity in the presence of the three antifreeze peptides, respectively, significantly higher than that of the blank control (32%). Molecular docking revealed that hydrogen bonding was the primary driving force for the stable binding of these antifreeze peptides to ice crystal planes. These findings offer an efficient strategy for converting tilapia processing by-products into high-value commercial antifreeze agents.

Selenium-enriched proteins are the primary form of selenium in plants and animals. Selenium-containing proteins contain various selenoamino acids, including selenocysteine, selenocystine, methyl selenocysteine and selenomethionine, which exert antioxidant, cognitive-enhancing, blood glucose regulating, and immunomodulatory effects. In addition, selenium-enriched proteins play a significant role in the treatment of inflammatory bowel disease by modulating immune activity, repairing the intestinal barrier and maintaining intestinal flora balance. This article reviews the functional properties and species of food-borne selenium-enriched proteins and the methods for their quantitation, focusing on their bioactive mechanisms and synergistic effects with other nutrients. Meanwhile, this review presents an outlook on their potential for application in the treatment and alleviation of inflammatory bowel disease, with a view to providing precise theoretical support for the functional development of selenium-enriched proteins.

This study investigated the paracellular diffusion of egg white-derived antihypertensive peptide RVPSL using a 4D-DIA proteomics approach. The 775 differentially expressed proteins were identified after RVPSL transport. Gene Ontology enrichment analysis indicated that five key proteins (i.e., CLDN1, ECT2, EGFR, SYNPO, and ACTN4) associated with bicellular tight junction assembly, actin filament binding, and actin binding may affect the paracellular diffusion of RVPSL. The egg white-derived peptide RVPSL may trigger the opening of tight junctions by down-regulating the expression of CLDN1 and ECT2 proteins, up-regulating the EGFR protein expression, and may promote the restoration of tight junctions by up-regulating the expression of SYNPO and ACTN4 proteins, thereby enabling paracellular diffusion. Furthermore, the retrograde endocannabinoid signaling pathway may regulate the paracellular diffusion of egg white-derived peptide RVPSL by affecting the expression of tight junction-related proteins. The study provides new ideas and insights to understand the intestinal absorption of egg white-derived peptides to enhance the health-promoting effect.

In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the structures of peptides in Colla Corii Asini (Ejiao) subjected to simulated gastrointestinal digestion. The peptides were screened for their anti-hypertensive, anti-Alzheimer, and anti-tumor potential by molecular docking. The results showed that 519 active peptides with molecular mass ranging from 661.4 to 2851.4 Da were obtained from the digested products of Ejiao. These peptides were mainly derived from the enzymatic hydrolysis of collagen and hemoglobin. Peptides KGETGLR, SGLDGAKG, and ADGVAGPK were found to have the highest anti-hypertensive, anti-Alzheimer and anti-tumor potential. Hydrogen bond and electrostatic interactions played a vital role in the anti-hypertensive, anti-Alzheimer, and anti-tumor activities of the Ejiao peptides.

This study applied 4D-fast data-independent acquisition (DIA) quantitative proteomics for the identification and functional analysis of the differentially expressed proteins between selenium-enriched and non-selenium-enriched eggs. A quantitative proteomic analysis of selenium-enriched eggs was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics. The relative quantification of proteins between groups was performed to explore the differential expression patterns of proteins, and protein functions and metabolic pathways were analyzed using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Proteomic analysis identified a total of 257 proteins, of which 251 were quantified. Forty-eight differentially expressed proteins were identified in egg white, with 28 being down-regulated and 20 being up-regulated. A total of 82 differentially expressed proteins were identified in egg yolk, with 58 being down-regulated and 24 being up-regulated. The expression levels of serine peptidase inhibitor, immunoglobulin-like domain-containing proteins, ovotransferrin, and mucin-6 were significantly higher in naturally selenium-enriched eggs than in non-selenium-enriched eggs, based on a comparative analysis of protein expression profiles. Go annotation and KEGG pathway enrichment analyses revealed that proteins associated with immune regulation, antibacterial activity, and antioxidant functions were significantly higher expressed in naturally selenium-enriched eggs compared with non-selenium-enriched eggs. These findings provide a scientific basis for understanding the difference in nutritional value between selenium-enriched eggs and non-selenium-enriched eggs, as well as the underlying molecular mechanisms.

Mizuhopecten yessoensis-derived angiotensin converting enzyme (ACE) inhibitory peptide Asn-Cys-Trp (NCW) has been found that had a significantly in vivo antihypertensive effect. However, the special mechanism of peptide NCW for lowing blood pressure has not been fully elucidated. This study aimed to screen the key targets and elucidate the antihypertensive mechanism of based on the network pharmacology and molecular docking. A total of 70 potential antihypertensive targets of peptide NCW were identified, which were mainly enriched in Regulation of blood pressure, Positive regulation of smooth muscle cell proliferation, and other biological processes; Plasma membrane, Extracellular exosome, and other cellular components; Endopeptidase activity, Zinc ion binding, and other molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that lipid and atherosclerosis pathway, relaxin signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were the key pathways for peptide NCW to regulate the potential antihypertensive targets. Eleven potential key antihypertensive targets were screened via topology analysis of protein and protein interaction network, i.e., albumin (ALB), matrix metallopeptidase 9 (MMP9), MMP2, insulin like growth factor 1, AKT serine/threonine kinase 1 (IGF1), ACE, nitric oxide synthase 3 (NOS3), peroxisome proliferator activated receptor gamma (PPARG), epidermal growth factor receptor (EGFR), catalase (CAT), and renin (REN). In addition, molecular docking results showed that the peptide NCW had high affinities with these potential key antihypertensive targets, and hydrogen bonds were the key interaction forces between the peptide NCW and targets. This study provided a theoretical basis for the multi-target and multi-pathway prevention and improvement of hypertension with peptide NCW.

Bitter taste receptors (T2Rs) perform crucial role in the sensation of bitterness, especially the T2R14 that can widely perceive the bitterness. In this study, egg protein-derived T2R14 blocking peptides were identified using physicochemical property prediction, molecular docking, molecular dynamic simulation, and in vitro validation. The ‘-CDOCKER_ENERGY’ values of peptides CQR and CGSR were higher than the positive control LEGSLE, were 314.26 and 294.85 kJ/mol, respectively. The results showed that the half inhibitory concentration (IC₅₀) of the egg protein-derived peptides CQR and CGSR were 382.87 and 370.13 μmol/L, respectively, and higher than that of the positive control LEGSLE. The molecular docking results showed that the conventional hydrogen bond interaction was the main binding force between T2R14 and peptides (i.e., CQR and CGSR). In summary, the novel T2R14 blocking peptides CQR and CGSR were identified, and aided in understanding the mechanism responsible for T2R14 blocking peptides. This study provides further guidance to block T2R14 and may address the bitterness problem in the food industry.

The angiotensin-converting enzyme (ACE) inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects, however, its anti-hypertensive mechanism is still not fully clarified. This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the anti-hypertensive mechanism of peptide NCW in spontaneously hypertensive rats (SHRs). Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHR-Untreated groups. A total of 85 metabolites were differentially regulated, and 16 metabolites were identified as potential kidney biomarkers, e.g., 3-hydroxybutyrate, malonic acid, deoxycytidine, and L-aspartic acid. The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism, folate related pathways, synthesis and degradation of ketone bodies, pyrimidine metabolism, β-alanine metabolism, and retinal metabolism.

Oncorhynchus mykiss is delicious and contains abundant flavor substances. However, few studies focused on umami peptides of O. mykiss. In the current work, umami peptides derived from O. mykiss were identified using virtual screening, molecular docking, and electronic tongue analysis. First, the O. mykiss protein was hydrolyzed using the PeptideCutter online enzymolysis program. Subsequently, water-soluble and toxicity screening were performed by Innovagen and ToxinPred software, respectively. The potential peptides were docked with umami receptor T1R1/T1R3. Furthermore, taste properties of potential peptides were validated by electronic tongue. Docking results suggested that the three tetrapeptide EANK, EEAK, and EMQK could enter the binding pocket in the T1R1 cavity, wherein Arg151, Asp147, Gln52, and Arg277 may play key roles in the production of umami taste. Electronic tongue results showed that the umami value of EANK, EEAK, and EMQK were stronger than monosodium glutamate. This work provides a new insight for the screening of umami peptides in O. mykiss.