School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China.
School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China; National Engineering Research Center of Seafood, Dalian 116034, PR China.
Food Res Int. 2022 Jul;157:111402. doi: 10.1016/j.foodres.2022.111402. Epub 2022 May 23.
The purpose of this study is to explore the effects of IVTNWDDMEK and VGPAGPRG, two angiotensin I-converting enzyme (ACE) inhibitory peptides purified from Volutharpa ampullacea perryi, on ACE's two domains and on nitric oxide (NO), endothelin-1(ET-1) production in human vascular endothelial cells (HUVECs). In addition, we sought to investigate the effects of these two peptides on HUVECs injury induced by HO. The results indicated that the inhibition of the ACE C-domain was significantly higher than that of the ACE N-domain by these two peptides. Molecular dynamics (MD) analysis revealed that the hydrogen bonds interactions between ACE and two peptides, the chelation between peptides and Zn both play important role, which might contribute significantly to the ACE inhibitory activity. Two peptides significantly increase NO and ET-1 production in a dose-dependent manner and protects against hydrogen peroxide-induced HUVEC cell injury. The reported results also show that two peptides up-regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1), and reduce the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA). Our study indicated that IVTNWDDMEK and VGPAGPRG could be potent ACE inhibitors and Volutharpa ampullacea perryi is a good source of bioactive peptides, which provided a theoretical basis for the broad application of two selected peptides as functional food with anti-hypertensive activity.
本研究旨在探讨从鲍鱼内脏中分离纯化得到的两个血管紧张素转化酶（ACE）抑制肽 IVTNWDDMEK 和 VGPAGPRG 对 ACE 两个结构域及对人血管内皮细胞（HUVEC）一氧化氮（NO）、内皮素-1（ET-1）产生的影响。此外，我们还研究了这两种肽对 HUVEC 损伤的影响。结果表明，这两种肽对 ACE C 结构域的抑制作用明显高于 ACE N 结构域。分子动力学（MD）分析表明，ACE 与两种肽之间的氢键相互作用、肽与锌的螯合作用对 ACE 抑制活性都起着重要作用。两种肽均可显著增加 NO 和 ET-1 的产生，呈剂量依赖性，并可防止过氧化氢诱导的 HUVEC 细胞损伤。报告结果还表明，两种肽可上调核因子红细胞 2 相关因子（Nrf2）和血红素加氧酶-1（HO-1）的表达，减少活性氧（ROS）和丙二醛（MDA）的积累。本研究表明，IVTNWDDMEK 和 VGPAGPRG 可能是有效的 ACE 抑制剂，鲍鱼内脏是生物活性肽的良好来源，为两种选定的肽作为具有降血压活性的功能性食品的广泛应用提供了理论依据。
