Xiang Huan, Huang Hui, Shao Yanqiu, Hao Shuxian, Li Laihao, Wei Ya, Chen Shengjun, Zhao Yongqiang
Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural Affairs, National R&D Center for Aquatic Product Processing, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, China.
Front Nutr. 2024 Dec 5;11:1462656. doi: 10.3389/fnut.2024.1462656. eCollection 2024.
Hypertension is a chronic cardiovascular disease, which can trigger some disease such as heart failure, loss of vision or kidney. There were various peptides derived from food that are recognized for their ability to inhibit ACE activity, potentially leading to a reduction in blood pressure levels . The primary objective of this research is to discover ACE inhibitory peptides from protein hydrolysates of eel bone collagen (EBCHs).
To begin, EBCHs were created and then divided through the process of ultrafiltration. The second step involved screening of peptides capable of inhibiting ACE by combining peptidomics and molecular docking. And the mechanism by which ACE interacts with peptides has been studied. Finally, the hypotensive mechanism of identified peptide through cell experiments with HUVEC (Human Umbilical Vein Endothelial Cells).
Eel () bone collagen was hydrolyzed by alcalase and the hydrolysate was separated into three fractions, among which the F2 displayed a higher level of ACE inhibitory activity. According to molecular docking calculations, a total of 615 peptides were identified through nano-HPLC-MS/MS, with the prediction of seven newly discovered ACE inhibitory peptides (PMGPR, GPMGPR, GPAGPR, GPPGPPGL, GGPGPSGPR, GPIGPPGPR, GPSGAPGPR). Notably, GPPGPPGL had the lowest IC value of 535.84 μM among the identified peptides, indicating its potency as an ACE inhibitor. The ACE S2 pocket formed hydrogen and hydrophobic interactions with GPPGPPGL. Lineweaver-Burk plots revealed that GPPGPPGL competitively bound to ACE's active site residues. Treatment with GPPGPPGL significantly increased nitric oxide secretion ( < 0.01) and decreased endothelin-1 (ET-1) production in HUVECs.
Our findings suggest that combining peptidomics with molecular docking is effective for rapidly screening ACE inhibitory peptides. Future studies should assess the bioavailability and activity of the identified peptide GPPGPPGL from EBCHs.
高血压是一种慢性心血管疾病，可引发心力衰竭、视力丧失或肾脏疾病等。有多种源自食物的肽因其抑制ACE活性的能力而受到认可，这可能导致血压水平降低。本研究的主要目的是从鳗鱼骨胶原蛋白（EBCHs）的蛋白水解物中发现ACE抑制肽。
首先，制备EBCHs，然后通过超滤过程进行分离。第二步是通过结合肽组学和分子对接筛选能够抑制ACE的肽。并且研究了ACE与肽相互作用的机制。最后，通过人脐静脉内皮细胞（HUVEC）的细胞实验研究鉴定出的肽的降压机制。
用碱性蛋白酶水解鳗鱼（）骨胶原蛋白，水解产物分为三个部分，其中F2显示出较高水平的ACE抑制活性。根据分子对接计算，通过纳米高效液相色谱-串联质谱法共鉴定出615种肽，预测有7种新发现的ACE抑制肽（PMGPR、GPMGPR、GPAGPR、GPPGPPGL、GGPGPSGPR、GPIGPPGPR、GPSGAPGPR）。值得注意的是，在鉴定出的肽中，GPPGPPGL的IC值最低，为535.84μM，表明其作为ACE抑制剂的效力。ACE的S2口袋与GPPGPPGL形成氢键和疏水相互作用。Lineweaver-Burk图显示GPPGPPGL竞争性结合到ACE的活性位点残基上。用GPPGPPGL处理显著增加了HUVECs中一氧化氮的分泌（<0.01）并降低了内皮素-1（ET-1）的产生。
我们的研究结果表明，将肽组学与分子对接相结合对于快速筛选ACE抑制肽是有效的。未来的研究应评估从EBCHs中鉴定出的肽GPPGPPGL的生物利用度和活性。
