Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi 122100, Vietnam.
Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi 122100, Vietnam.
Molecules. 2022 Jul 14;27(14):4505. doi: 10.3390/molecules27144505.
Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K1.1 and Ca1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba currents through Ca1.2 channels (I) were blocked in a concentration-dependent manner by sativanone, 3'--methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7--[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased I. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.
高血压是心血管疾病的一个风险因素，而心血管疾病是世界上发病率和死亡率的主要原因。在寻找能够靶向 K1.1 和 Ca1.2 通道的新分子的过程中，评估了一系列从 Prain 的心材、根和叶中提取的类黄酮在体外对血管的影响，Prain 广泛用于传统医学。使用大鼠主动脉环、尾动脉肌细胞以及对接和分子动力学模拟来分析它们对这些通道的影响。芒柄花素、奥罗波醇、松属素和大豆黄素表现出明显的肌松弛活性，特别是在受中等而不是高浓度 KCl 刺激的环中。Sativanone、3'--甲基violanone、松属素和大豆黄素以浓度依赖性方式阻断 Ca1.2 通道的 Ba 电流（I），而 ambocin 则刺激 I。Sativanone、dalsissooside 和 eriodictyol 抑制，而 tectorigenin 7--[β-D-阿比呋喃糖基-(1→6)-β-D-葡萄糖苷]、ambocin、butin 和大豆黄素增加 I。计算机模拟分析表明，大豆黄素、sativanone 和松属素与两种通道的靶传感区域具有高亲和力结合，为它们的潜在作用机制提供了深入了解。总之，Prain 是开发新型抗高血压药物的单功能和双功能血管活性支架的有价值来源。
