Production, identification, in silico analysis, and cytoprotection on H2O2-induced HUVECs of novel angiotensin-I-converting enzyme inhibitory peptides from Skipjack tuna roes

Wang-Yu Zhu; Yu-Mei Wang; Ming-Xue Ge; Hua-Wei Wu; Shuo-Lei Zheng; Huai-Yu Zheng; Bin Wang

doi:10.3389/fnut.2023.1197382

Production, identification, in silico analysis, and cytoprotection on H₂O₂-induced HUVECs of novel angiotensin-I-converting enzyme inhibitory peptides from Skipjack tuna roes

Front Nutr. 2023 Jul 12:10:1197382. doi: 10.3389/fnut.2023.1197382. eCollection 2023.

Authors

Wang-Yu Zhu¹, Yu-Mei Wang², Ming-Xue Ge², Hua-Wei Wu³, Shuo-Lei Zheng², Huai-Yu Zheng¹, Bin Wang²

Affiliations

¹ Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang Province, Zhoushan, China.
² Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, China.
³ Ningbo Today Food Co., Ltd., Ningbo, China.

Abstract

Background: Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by disposal and elimination, the valorization of nutritional ingredients from these by-products receives increasing attention.

Objective: This study was to identify the angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) peptides from roe hydrolysate of Skipjack tuna (Katsuwonus pelamis) and evaluate their protection functions on H₂O₂-induced human umbilical vein endothelial cells (HUVECs).

Methods: Protein hydrolysate of tuna roes with high ACEi activity was prepared using flavourzyme, and ACEi peptides were isolated from the roe hydrolysate using ultrafiltration and chromatography methods and identified by ESI/MS and Procise Protein/Peptide Sequencer for the N-terminal amino acid sequence. The activity and mechanism of action of isolated ACEi peptides were investigated through molecular docking and cellular experiments.

Results: Four ACEi peptides were identified as WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12), respectively. The affinity of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) with ACE was -8.590, -9.703, -9.325, and -8.036 kcal/mol, respectively. The molecular docking experiment elucidated that the significant ACEi ability of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) was mostly owed to their tight bond with ACE's active sites/pockets via hydrophobic interaction, electrostatic force and hydrogen bonding. Additionally, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could dramatically elevate the Nitric Oxide (NO) production and bring down endothelin-1 (ET-1) secretion in HUVECs, but also abolish the opposite impact of norepinephrine (0.5 μM) on the production of NO and ET-1. Moreover, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could lower the oxidative damage and apoptosis rate of H₂O₂-induced HUVECs, and the mechanism indicated that they could increase the content of NO and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the generation of reactive oxygen species (ROS) and malondialdehyde (MDA).

Conclusion: WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.

Keywords: Skipjack tuna (Katsuwonus pelamis); angiotensin-I-converting enzyme; cytoprotection; endothelial cells; oxidative damage; peptide; roe.