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Eulophia macrobulbon extract relaxes rat isolated pulmonary artery and protects against monocrotaline-induced pulmonary arterial hypertension

Wisutthathum, Sutthinee, Demougeot, Céline, Totoson, Perle, Adthapanyawanich, Kannika, Ingkaninan, Kornkanok, Temkitthawon, Prapapan, Chootip, Krongkarn
Phytomedicine 2018 v.50 pp. 157-165
4-aminopyridine, Orchidaceae, active ingredients, antihypertensive effect, aorta, calcium, endothelium, glibenclamide, hypertension, hypertrophy, indomethacin, lungs, median effective concentration, monocrotaline, myocytes, nitric oxide, nitroprusside, phenanthrenes, phenylephrine, pulmonary artery, rats, vasodilation
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-(4ʹ-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 (EC50 = 0.17 mg/ml, Emax ∼ 94%) but less so for aorta (EC50 = 0.51 mg/ml, Emax ∼ 62%), suggesting some selectivity towards the pulmonary circulation. PA vasorelaxation was reduced by endothelial removal or NG-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 Ca2+application, and inhibited intracellular Ca2+release 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 Ca2+-mobilization, and reduced PA wall thickness and right ventricular hypertrophy.