Ex Vivo Study of the Vasorelaxant Activity Induced by Phenanthrene Derivatives Isolated from <i>Maxillaria densa</i>

Rendón-Vallejo, Priscila; Hernández-Abreu, Oswaldo; Vergara-Galicia, Jorge; Millán‐Pacheco, César; Mejía, Armando; Ibarra-Barajas, Maximiliano; Estrada‐Soto, Samuel

doi:10.1021/np300508v

Cited by 25 publications

(17 citation statements)

References 18 publications

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“…Interestingly, very similar phenanthrene derivatives were shown to possess myorelaxing activity either in rat ileum [4] or in rat aorta rings [16]. In the latter, the results obtained were particularly similar to those here presented (namely, relaxation of norepinephrine-, high K + -and FPL 64176-induced contractions); thus, Ca V 1.2 channel blockade and K + channel opening were claimed.…”

Section: Discussionsupporting

confidence: 86%

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

et al. 2020

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Five compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

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Section: Discussionsupporting

confidence: 86%

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

et al. 2020

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“…Contrary to large vessels in which NO is the major endothelium-derived factor ( Wu et al, 1993 ), EDH is thought to play a major role in the endothelium-dependent vasorelaxation in resistance vessels ( Félétou and Vanhoutte, 1999 ; Chauhan et al, 2003 ). Of interest, albeit beneficial vascular effects such as a relaxant effect on aorta ( Rendón-Vallejo et al, 2012 ) or an inhibitory effect on expression of adhesion molecules in isolated VSMC have been reported with various phenanthrene derivatives ( Huang et al, 2008 ; Choi et al, 2012 ; Lo et al, 2017 ), to the best of our knowledge, our study is the first to show that a benzylated phenanthrene derivative improves vascular function.…”

Section: Discussionmentioning

confidence: 68%

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

et al. 2018

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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).

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“…The stimulation was done three times at 30 min intervals before starting the experiments. The absence of endothelium was confirmed by the lack of the relaxant response induced by carbachol (1 µM) in the last stimulation [5][6][7].…”

Section: Functional Studiesmentioning

confidence: 90%

6-Amino-3-Methyl-4-(2-nitrophenyl)-1,4-Dihydropyrano[2,3-c]Pyrazole-5-Carbonitrile Shows Antihypertensive and Vasorelaxant Action via Calcium Channel Blockade

et al. 2021

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Several 4H-pyran derivatives were designed and synthesized previously as vasorelaxant agents for potential antihypertensive drugs. In this context, the objective of the present investigation was to determine the functional mechanism of vasorelaxant action of 6-amino-3-methyl-4-(2-nitrophenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) and its in vivo antihypertensive effect. Thus, compound 1 showed significant vasorelaxant action on isolated aorta rat rings pre-contracted with serotonin or noradrenaline, and the effect was not endothelium-dependent. Compound 1 induced a significant relaxant effect when aortic rings were contracted with KCl (80 mM), indicating that the main mechanism of action is related to L-type calcium channel blockade. Last was corroborated since compound 1 induced a significant concentration-dependent lowering of contraction provoked by cumulative CaCl2 adding. Moreover, compound 1 was capable to block the contraction induced by FPL 64176, a specific L-type calcium channel agonist, in a concentration-dependent manner. On the other hand, docking studies revealed that compound 1 interacts on two possible sites of the L-type calcium channel and it had better affinity energy (−7.80+/−0.00 kcal/mol on the best poses) than nifedipine (−6.86+/−0.14 kcal/mol). Finally, compound 1 (50 mg/kg) showed significant antihypertensive activity, lowering the systolic and diastolic blood pressure on spontaneously hypertensive rats (SHR) without modifying heart rate.

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Ex Vivo Study of the Vasorelaxant Activity Induced by Phenanthrene Derivatives Isolated from Maxillaria densa

Cited by 25 publications

References 18 publications

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

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

6-Amino-3-Methyl-4-(2-nitrophenyl)-1,4-Dihydropyrano[2,3-c]Pyrazole-5-Carbonitrile Shows Antihypertensive and Vasorelaxant Action via Calcium Channel Blockade

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