PMID- 35938100 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220809 IS - 2296-861X (Print) IS - 2296-861X (Electronic) IS - 2296-861X (Linking) VI - 9 DP - 2022 TI - Novel angiotensin-converting enzyme inhibitory peptides from tuna byproducts-milts: Preparation, characterization, molecular docking study, and antioxidant function on H(2)O(2)-damaged human umbilical vein endothelial cells. PG - 957778 LID - 10.3389/fnut.2022.957778 [doi] LID - 957778 AB - 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 IC(50) 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 H(2)O(2) 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. CI - Copyright (c) 2022 Suo, Zheng, Chi, Luo and Wang. FAU - Suo, Shi-Kun AU - Suo SK AD - Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan, China. FAU - Zheng, Shuo-Lei AU - Zheng SL AD - Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan, China. FAU - Chi, Chang-Feng AU - Chi CF AD - National and Provincial Joint Laboratory of Exploration and Utilization of Marine Aquatic Genetic Resources, National Engineering Research Center of Marine Facilities Aquaculture, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan, China. FAU - Luo, Hong-Yu AU - Luo HY AD - Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan, China. FAU - Wang, Bin AU - Wang B AD - Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan, China. LA - eng PT - Journal Article DEP - 20220722 PL - Switzerland TA - Front Nutr JT - Frontiers in nutrition JID - 101642264 PMC - PMC9355146 OTO - NOTNLM OT - angiotensin-I-converting enzyme (ACE) OT - antihypertensive function OT - antioxidant activity OT - milt OT - peptide OT - skipjack tuna (Katsuwonus pelamis) EDAT- 2022/08/09 06:00 MHDA- 2022/08/09 06:01 PMCR- 2022/01/01 CRDT- 2022/08/08 04:14 PHST- 2022/05/31 00:00 [received] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/08/08 04:14 [entrez] PHST- 2022/08/09 06:00 [pubmed] PHST- 2022/08/09 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fnut.2022.957778 [doi] PST - epublish SO - Front Nutr. 2022 Jul 22;9:957778. doi: 10.3389/fnut.2022.957778. eCollection 2022.