School of Biology & Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215101, China.
Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, Lanzhou 730030, China.
Food Chem. 2023 Feb 1;401:134127. doi: 10.1016/j.foodchem.2022.134127. Epub 2022 Sep 7.
In the present study, Ulva prolifera, an edible alga, was used to prepare angiotensin-I converting enzyme (ACE) inhibitory peptide. The algae protein was isolated and later hydrolyzed by five commercial enzymes (alcalase, papain, pepsin, trypsin, neutral protease), either individually or in combination. Hydrolysate, with the highest in vitro ACE inhibitory activity, was processed using the Sephadex-G100, ultrafiltration, HPLC-Q-TOF-MS, ADMET screening and molecular docking, respectively. The ACE inhibitory peptide DIGGL with a IC value of 10.32 ± 0.96 μM was then identified. The peptide against ACE by a non-competitive mode and mainly attributable to the three Conventional Hydrogen Bonds. It could activate Endothelial nitric oxide synthase activity in NO generation and reduce Endothelin-1 secretion induced by Angiotensin II in Human umbilical vein endothelial cells. Meanwhile, DIGGL could promote mice splenocytes proliferation, which was also effective when co-incubated with Con A or LPS, respectively. Besides, the anti-ACE peptide could remain active during the digestion of gastrointestinal proteases (pepsin-trypsin) in vitro.
在本研究中，使用可食用海藻石莼来制备血管紧张素转化酶（ACE）抑制肽。将藻类蛋白分离出来，然后用五种商业酶（碱性蛋白酶、木瓜蛋白酶、胃蛋白酶、胰蛋白酶、中性蛋白酶）单独或组合水解。用 Sephadex-G100、超滤、HPLC-Q-TOF-MS、ADMET 筛选和分子对接分别处理体外 ACE 抑制活性最高的水解产物。然后鉴定出 ACE 抑制肽 DIGGL，其 IC 值为 10.32±0.96μM。该肽通过非竞争性模式抑制 ACE，主要归因于三个常规氢键。它可以激活内皮型一氧化氮合酶活性，促进 NO 的产生，并降低血管紧张素 II 诱导的人脐静脉内皮细胞内皮素-1的分泌。同时，DIGGL 可促进小鼠脾细胞增殖，与 ConA 或 LPS 分别孵育时也具有活性。此外，该抗 ACE 肽在体外胃肠道蛋白酶（胃蛋白酶-胰蛋白酶）消化过程中仍保持活性。
