Hunan Provincial Key Laboratory for Forestry Biotechnology & International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology , Central South University of Forestry and Technology , Changsha , 410004 , China.
College of Food and Chemical Engineering , Shaoyang University , Shaoyang , 422000 , China.
J Agric Food Chem. 2019 Jul 24;67(29):8149-8159. doi: 10.1021/acs.jafc.9b02276. Epub 2019 Jul 11.
() has been widely used in Asia to treat hypertension, but the active substances responsible for its antihypertensive effects remain unclear. Using the well-established angiotensin I-converting enzyme (ACE) as a target, we identified three ACE inhibitory peptides (ACEIPs), Gln-Leu-Val-Pro (QLVP), Gln-Asp-Val-Leu (QDVL), and Gln-Leu-Asp-Leu (QLDL), which account for the antihypertensive activity of . Notably, QLVP worked in a mixed-type manner against ACE with an IC value of 127.9 μmol/L. Molecular dynamics simulation suggested that the potent charge energy of QLVP, which interacted with Gln242 and Lys472 of ACE via a hydrogen bond and a salt bridge, potentially contributed to ACE inhibitory activity. Moreover, QLVP markedly activated angiotensin I-mediated phosphorylation of endothelial nitric oxide synthase in human umbilical vein endothelial cells and partly reduced mRNA and protein expression of the vasoconstrictor factor endothelin-1. This is the first report of the antihypertensive activity of small ACEIPs originating from mycelia, paving the way for the possible application of these peptides as potent drug candidates for treating hypertension.
（）在亚洲被广泛用于治疗高血压，但负责其降压作用的活性物质仍不清楚。我们以成熟的血管紧张素转化酶（ACE）为靶点，鉴定出三个 ACE 抑制肽（ACEIPs），即 Gln-Leu-Val-Pro（QLVP）、Gln-Asp-Val-Leu（QDVL）和 Gln-Leu-Asp-Leu（QLDL），它们是 发挥降压作用的原因。值得注意的是，QLVP 以混合抑制方式作用于 ACE，IC 值为 127.9 μmol/L。分子动力学模拟表明，QLVP 与 ACE 的 Gln242 和 Lys472 之间通过氢键和盐桥相互作用，具有很强的电荷能量，这可能是 ACE 抑制活性的原因。此外，QLVP 显著激活了人脐静脉内皮细胞中血管紧张素 I 介导的内皮型一氧化氮合酶磷酸化，并部分降低了血管收缩因子内皮素-1 的 mRNA 和蛋白表达。这是源自 菌丝体的小 ACEIPs 具有降压活性的首次报道，为这些肽作为治疗高血压的潜在有效药物候选物的应用铺平了道路。
