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

Abstract

BackgroundExceeding 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.ObjectiveThis 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).MethodsProtein 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.ResultsFour 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).ConclusionWGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.

Recent progress of food‐derived bioactive peptides: Extraction, purification, function, and encapsulation

“…Antihypertensive peptides derived from food proteins exhibit the capacity to reduce blood pressure in hypertensive patients (Zhang et al, 2018a) inhibitory peptides Ala-Ser-Pro-Tyr-Ala-Phe-Gly-Leu with IC 50 value of 1.08 × 10 −7 mol L −1 from mushrooms by sulfuric acid hydrolysis and indicated that mushrooms could be exploited as multifunctional ingredients for drugs or functional foods against osteoarthritis and hypertension (Zhang et al, 2017). In addition, peptides with ACE inhibitory activity were also extracted from marine food sources, such as Skipjack tuna muscles and roes as well as Mytilus edulis demonstrating their potential as functional foods against hypertension and cardiovascular diseases (Suo et al, 2022a;Zheng et al, 2022;Zhu et al, 2023).…”

Trash to Treasure: An Up-to-Date Understanding of the Valorization of Seafood By-Products, Targeting the Major Bioactive Compounds

“…Four peptides among the fifteen extracted peptides showed remarkable ACE-inhibitory activity. [79] Chinese sturgeon (Acipenser sinensis)…”

Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from the Collagens of Monkfish (Lophius litulon) Swim Bladders: Isolation, Characterization, Molecular Docking Analysis and Activity Evaluation

“…RP-HPLC is an extremely efficient technology for isolating ACEi peptides according to their RT, and the RT of separated ACEi peptides can be modulated by adjusting the ratio of polar solvent (such as trifluoroacetic acid (TFA), methanol, ethyl alcohol and acetonitrile) in the mobile phase [30,32,64]. Therefore, ACEi peptides have been separated using RP-HPLC from protein hydrolysates of T. bimaculatus [28], R. philippinarum [67], Skipjack tuna roes [31], M. edulis [30], Kuruma shrimp [66], pearl oyster [68], Pyropia pseudolinearis [69], squilla [39], hybrid groupers [41], Arthrospira platensis [70], etc.…”

“…[29,30]. However, the World Health Organization (WHO) reports that the number of people with hypertension will increase from 1.28 billion to 1.56 billion by 2030 [31]. ACE can modify angiotensin (Ang) I to active Ang II to upregulate blood pressure by inactivating the vasodilator bradykinin.…”

“…The search for safer ACEi drugs from animals and plants can offer a viable alternative to chemosynthetic ACEi drugs for lowering high blood pressure [33][34][35]. Therefore, the preparation of ACEi peptides from fish and fish by-products has become a focal point for researchers, and some ACEi peptides have been prepared from different marine organisms, such as Pacific cod [36], Takifugu bimaculatus [28], Skipjack tuna [37,38], squilla [39], Alaska pollack [40], hybrid groupers [41], miiuy croakers [42], Kuruma shrimp [31], Cobia [43] and Antarctic krill [44].…”