Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.
Graduate University of Science and Technology, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.
Planta Med. 2020 Mar;86(4):284-293. doi: 10.1055/a-1099-2929. Epub 2020 Jan 28.
species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of -(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of and to provide circular dichroism features of its absolute configuration. The vascular effects of -(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba currents through Ca1.2 channels (I) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. -(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor N-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. -(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(-)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, -(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited I in a concentration-dependent manner and significantly decreased the time constant of current inactivation. -(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the Ca1.2 channel subunit. In conclusion, species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.
树种的心材被广泛应用于传统医学，用于治疗各种心血管疾病，可能是血管活性物质的丰富来源。在越南，是一种特有树种。因此，本工作的目的是研究从树种的心材中分离得到的 (-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌的血管活性，并提供其绝对构型的圆二色性特征。通过在去内皮和完整内皮的大鼠主动脉环的等长条件下评估 (-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌对血管的影响，以及通过贴壁钳技术在单个大鼠尾主动脉心肌细胞中记录的 Ca1.2 通道（I）的全细胞 Ba 电流，评估 (-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌的血管舒张活性。(-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌对预先用苯肾上腺素受体激动剂收缩的去内皮和完整内皮环均显示出浓度依赖性的血管舒张活性。一氧化氮（NO）合酶抑制剂 N-硝基-L-精氨酸甲酯和环氧化酶抑制剂吲哚美辛均不影响其松弛活性。(-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌诱导的血管舒张作用被（S）-（-）-Bay K 8644 拮抗，不受四乙铵加格列本脲影响。在贴壁钳实验中，(-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌浓度依赖性地抑制 I，显著降低电流失活的时间常数。(-)-3'-羟基-2,4,5-三甲氧基二氢贝壳杉醌可能通过分子建模和对接模拟到 Ca1.2 通道的 亚基，稳定通道处于关闭状态。综上所述，树种可能是潜在有用的新型抗高血压药物开发的药物来源。
