Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
Phytomedicine. 2018 Nov 15;50:157-165. doi: 10.1016/j.phymed.2018.05.014. Epub 2018 May 22.
Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature.
To pharmacologically characterize the vascular actions of EM ethanolic extract and its active compound, 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol using isolated pulmonary arteries (PA) from rats having pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). PA were fixed and prepared for histology.
EM extract relaxed PA (EC = 0.17 mg/ml, E ∼ 94%) but less so for aorta (EC = 0.51 mg/ml, E ∼ 62%), suggesting some selectivity towards the pulmonary circulation. PA vasorelaxation was reduced by endothelial removal or N-nitro-L-arginine methyl ester, but unaffected by indomethacin, apamin +charybdotoxin, 4-aminopyridine, glibenclamide, iberiotoxin, or 1H - [1,2,4]oxadiazolo[4,3-a]quinoxalin -1- one. Sodium nitroprusside-induced relaxation was enhanced by EM extract, probably via PDE5 inhibition. EM extract reduced contractions evoked by extracellular Caapplication, and inhibited intracellular Carelease activated by phenylephrine. The phenanthrene relaxed PA independently of the endothelium. MCT thickened walls and decreased lumens of PA, and hypertrophied right ventricular myocytes, effects ameliorated by 3 weeks of oral sildenafil (20 mg/kg) or EM extract (15, 450 or 1000 mg/kg).
PAH is improved by EM extract acting through PA relaxation mediated through endothelial NO, reduced Ca-mobilization, and reduced PA wall thickness and right ventricular hypertrophy.
野生兰花 Eulophia macrobulbon（EM）提取物抑制磷酸二酯酶 5（PDE5），表明其可能优先扩张肺血管。
使用来自野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠的离体肺血管（PA），对 EM 乙醇提取物及其活性化合物 1-（4'-羟基苄基）-4,8-二甲氧基菲-2,7-二醇的血管作用进行药理学表征。PA 被固定并准备进行组织学检查。
EM 提取物松弛 PA（EC = 0.17 mg/ml，E 约 94%），但对主动脉的松弛作用较小（EC = 0.51 mg/ml，E 约 62%），表明对肺循环有一定的选择性。PA 血管舒张作用被内皮去除或 N-硝基-L-精氨酸甲酯降低，但不受吲哚美辛、阿帕米+沙利度胺、4-氨基吡啶、格列本脲、伊贝替定或 1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮影响。硝普钠诱导的松弛作用被 EM 提取物增强，可能通过 PDE5 抑制。EM 提取物减少细胞外 Ca 应用引起的收缩，并抑制由苯肾上腺素激活的细胞内 Ca 释放。菲酚独立于内皮松弛 PA。MCT 使 PA 壁变厚并减少管腔，使右心室心肌细胞肥大，这些作用可通过 3 周口服西地那非（20 mg/kg）或 EM 提取物（15、450 或 1000 mg/kg）得到改善。
EM 提取物通过介导内皮 NO、减少 Ca 动员、减少 PA 壁厚度和右心室肥厚的 PA 舒张作用来改善 PAH。
