Vasorelaxant and Hypotensive Effects of an Ethanolic Extract of Eulophia macrobulbon and Its Main Compound 1-(4′-Hydroxybenzyl)-4,8-Dimethoxyphenanthrene-2,7-Diol

Abstract

Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat inflammation, cancer, and cardio-metabolic diseases. The aim of the study was to investigate the vasorelaxant effect of ethanolic Eulophia macrobulbon (EM) extract and its main phenanthrene on rat isolated mesenteric artery and to investigate the hypotensive effect of EM.Methods: The vasorelaxant effects of EM extract or phenanthrene and the underlying mechanisms were evaluated on second-order mesenteric arteries from Sprague Dawley rats. In addition, the acute hypotensive effect was evaluated in anesthetized rats infused with cumulative concentrations of the EM extract.Results: Both EM extract (10-4–1 mg/ml) and phenanthrene (10-7–10-4 M) relaxed endothelium-intact arteries, an effect that was partly reduced by endothelium removal (p < 0.001). A significant decrease in the relaxant effect of the extract and the phenanthrene was observed with L-NAME and apamin/charybdotoxin in endothelium-intact vessels, and with iberiotoxin in denuded vessels. SNP (sodium nitroprusside)-induced relaxation was significantly enhanced by EM extract and phenanthrene. By contrast, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one), 4-aminopyridine and glibenclamide (endothelium-denuded vessels) and indomethacin (endothelium-intact vessels) had no effect. In calcium-free solution, both the EM extract and phenanthrene inhibited extracellular Ca2+-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca2+ release sensitive to PE. The acute infusion of EM extract (20 and 70 mg/kg) induced an immediate and transient dose-dependent hypotensive effect.Conclusion: The ethanolic extract of EM tubers and its main active compound, 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (phenanthrene) induced vasorelaxant effects on rat resistance vessels, through pleiotropic effects including endothelium-dependent effects (NOS activation, enhanced EDH production) and endothelium-independent effects (opening of KCa channels, inhibition of Ca2+ channels, inhibition of intracellular Ca2+ release and PDE inhibition).

Phenanthrene-enriched extract from Eulophia macrobulbon using subcritical dimethyl ether for phosphodiesterase-5A1 inhibition

“…More potent PDE5A1 inhibitory activity was observed at higher %HDP content (Table 3 ). This result supports that HDP is a suitable biomarker for the PDE5A1 inhibitory activity of this plant 17 . Moreover, PDE5A1 inhibitory activities of the extracts of the classical method were slightly stronger than those of the ultrasonic-assisted method in all solvents.…”

“…also displays PDE5A1 inhibition embodied in its phenanthrenes, particularly 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (HDP) 14 . E. macrobulbon relaxes human corpus cavernosal muscle in vitro 15 , 16 , relaxes rat pulmonary arteries ex vivo and reduces experimental pulmonary hypertension in rats 17 , 18 . Traditionally, E. macrobulbon is an aphrodisiac.…”

Vasodilatory Effects and Mechanisms of Action of Bacopa monnieri Active Compounds on Rat Mesenteric Arteries

“…In some experiments, endothelial cells were mechanically removed by gently rubbing the lumen with a stainless steel wire. The mesenteric rings were mounted on a pair of intraluminal wires in organ chambers containing physiological Krebs’ solution (mM): NaCl, 122; KCl, 5; [N-(2-hydroxyethyl) piperazine N’-(2-ethanesulfonic acid)] HEPES, 10; KH 2 PO 4 , 0.5; NaH 2 PO 4 , 0.5; MgCl 2 , 1; glucose, 11; and CaCl 2 , 1.8 (pH 7.3), at 37 °C and aerated [29,49,50,51]. The vessel segments were allowed to equilibrate for 1-h at a resting tension of 1–1.3 g during which the solution was replaced every 15 min.…”

Phenanthrene-Enriched Extract from Eulophia Macrobulbon Using Subcritical Dimethyl Ether for Phosphodiesterase-5A1 Inhibition

“…also displays PDE5A1 inhibition embodied in its phenanthrenes, particularly 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (HDP) (Temkitthawon et al 2017). E. macrobulbon relaxes human corpus cavernosal muscle in vitro (Preedapirom et al 2018, Jansakul et al 2019, relaxes rat pulmonary arteries ex vivo and reduces experimental pulmonary hypertension in rats (Wisutthathum et al 2018a, Wisutthathum et al 2018b). Traditionally, E. macrobulbon is an aphrodisiac.…”