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.

This study aimed to identify novel ACEI peptides from Larimichthys crocea titin using in silico approaches and to clarify the molecular interaction mechanism. The hydrolyzed peptides of titin were compared with known ACEI peptides in the AHTPDB and BIOPEP-UWM database. Furthermore, peptides were evaluated for their solubility, ADMET properties, △G (kcal/mol) values, and in vitro ACEI activity. Molecular mechanism of ACE-peptide was performed by molecular interactions and binding orientation study. The results revealed that IC₅₀ values of Trp-Ala-Arg(WAR) and Trp-Gln-Arg(WQR) were (31.2 ± 0.8) and (231.33 ± 0.02) μmol/L, respectively. The docking interactions result suggested that ACE-WAR and ACE-WQR complexes have same binding site, including the residues LYS511, TYR520, TYR523, HIS353, and HIS513. Molecular docking of two tripeptides WAR and WQR with ACE studies predicted their binding site and clarified the interaction between ACE and its inhibitors. The molecular docking data are consistent with the ACE inhibitory activity of the studied peptides. The results showed that Larimichthys crocea titin may be a valuable source for developing nutraceutical food.