Sutthinee Wisutthathum1, Céline Demougeot2, Perle Totoson3, Kannika Adthapanyawanich4, Kornkanok Ingkaninan5, Prapapan Temkitthawon5, Krongkarn Chootip6. 1. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. 2. PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France. Electronic address: cdemouge@univ-fcomte.fr. 3. PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France. 4. Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. 5. Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand. 6. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: krongkarnc@nu.ac.th.
Abstract
BACKGROUND: Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature. PURPOSE AND STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature. PURPOSE AND STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.
Authors: Seyed Vahid Jasemi; Hosna Khazaei; Ina Yosifova Aneva; Mohammad Hosein Farzaei; Javier Echeverría Journal: Front Pharmacol Date: 2020-03-12 Impact factor: 5.810