Novel angiotensin-converting enzyme inhibitory peptides from tuna byproducts—milts: Preparation, characterization, molecular docking study, and antioxidant function on H2O2-damaged human umbilical vein endothelial cells

Abstract

To prepare peptides with high angiotensin-converting enzyme (ACE) inhibitory (ACEi) activity, Alcalase was screened from five proteases and employed to prepare protein hydrolysate (TMH) of skipjack tuna (Katsuwonus pelamis) milts. Subsequently, 10 novel ACEi peptides were isolated from the high-ACEi activity TMH and identified as Tyr-Asp-Asp (YDD), Thr-Arg-Glu (TRE), Arg-Asp-Tyr (RDY), Thr-Glu-Arg-Met (TERM), Asp-Arg-Arg-Tyr-Gly (DRRYG), Ile-Cys-Tyr (ICY), Leu-Ser-Phe-Arg (LSFR), Gly-Val-Arg-Phe (GVRF), Lys-Leu-Tyr-Ala-Leu-Phe (KLYALF), and Ile-Tyr-Ser-Pro (IYSP) with molecular weights of 411.35, 404.41, 452.45, 535.60, 665.69, 397.48, 521.61, 477.55, 753.91, and 478.53 Da, respectively. Among them, the IC50 values of ICY, LSFR, and IYSP on ACE were 0.48, 0.59, and 0.76 mg/mL, respectively. The significant ACEi activity of ICY, LSFR, and IYSP with affinities of −7.0, −8.5, and −8.3 kcal/mol mainly attributed to effectively combining with the ACEi active sites through hydrogen bonding, electrostatic force, and hydrophobic interaction. Moreover, ICY, LSFR, and IYSP could positively influence the production of nitric oxide (NO) and endothelin-1 (ET-1) secretion in human umbilical vein endothelial cells (HUVECs) and weaken the adverse impact of norepinephrine (NE) on the production of NO and ET-1. In addition, ICY, LSFR, and IYSP could provide significant protection to HUVECs against H2O2 damage by increasing antioxidase levels to decrease the contents of reactive oxide species and malondialdehyde. Therefore, the ACEi peptides of ICY, LSFR, and IYSP are beneficial functional molecules for healthy foods against hypertension and cardiovascular diseases.

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs: Preparation, Identification, Antioxidant Activity, and Stability against Thermal, pH, and Simulated Gastrointestinal Digestion Treatments

“…In the experiment, the component (TCAH-I) with the lowest average molecular weight presented the strongest radical scavenging activity. The findings were consistent with the results in existing literature that small MW AP fractions of protein hydrolysates from different marine resources, such as bluefin leatherjacket skins [ 19 ], monkfish muscle [ 21 ], blue mussel [ 45 ], skate cartilages [ 55 ], Antarctic krill [ 50 ], and tuna milts [ 33 ] and heads [ 39 ], had the strongest radical scavenging abilities. In addition, chromatographic methods, including ion exchange chromatography, gel permeation chromatography, and RP-HPLC, are generally applied to purify peptides from hydrolysate fractions depending on their acidity/basicity, molecular size, and adsorption affinities [ 1 , 4 ].…”

“…Skipjack tuna ( Katsuwonus pelamis ) with annual catches of 3.2 × 10 6 tons is the most productive species of tuna. However, Skipjack tuna becomes the most important raw material for tuna canning industry due to its low value [ 32 , 33 ]. During tuna canning processing, about 50% Skipjack tuna were processed as byproducts, such as dark muscle, milt, bone/frame, scale, roe, head, and viscera [ 34 , 35 , 36 ].…”

“…Moreover, a variety of BPs were prepared from those byproducts and showed significant potential in the area of functional products. For example, the different peptides ICY, LSFR, IYSP, LPRS, SP, and VDRYF displayed significant blood pressure lowering activity by restraining angiotensin-I-converting enzyme (ACE) activity [ 33 , 36 , 37 ]. Other peptides, namely GPDGR, QDHKA, YEA, WMFDW, GADIVA, WMGPY, GAPGPQMV, EMGPA, DGPKGH, MLGPFPS, and AGPK presented the remarkable radical scavenging activity, lipid oxidation inhibition capability, and reducing power [ 24 , 38 , 39 , 40 ].…”

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms

“…Skipjack tuna is the most important raw material for canned aquatic products because of its high catch and low value [ 21 , 22 , 23 ]. It is worth paying attention that many bioactive peptides were prepared from skipjack tuna and its canning processing by-products [ 18 , 24 , 25 , 26 ].…”

Isolation, identification, molecular docking analysis, and cytoprotection of seven novel angiotensin I-converting enzyme inhibitory peptides from miiuy croaker byproducts-swim bladders

“…HUVECs were cultured in 96 well-plates at a density of 1 × 10 4 cells/cm 2 and treated with Cap (1 mM), NE (0.5 mM) or ACEi peptides (100 and 200 mM for MMP3 and MMP6) for 24 h, or incubated with both 200 mM ACEi peptide (MMP3 and MMP6) and NE (0.5 mM) for 24 h. The NO and ET-1 contents of HUVECs were determined after 24 h according to their assay kits as manufactures' protocol (Zhao et al, 2019b;Suo et al, 2022b).…”