Phenanthrenes from <i>Eulophia macrobulbon</i> as Novel Phosphodiesterase-5 Inhibitors

Temkitthawon, Prapapan; Changwichit, Kanokwan; Khorana, Nantaka; Viyoch, Jarupa; Suwanborirux, Khanit; Ingkaninan, Kornkanok

doi:10.1177/1934578x1701200121

Cited by 15 publications

(34 citation statements)

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“…Hook.f is naturally found in Thailand, Laos, Vietnam, Myanmar and Cambodia, and is traditionally used in local Thai medicine for treatment of insect bites and gangrene ( Schuster et al, 2017 ), this latter indication suggesting a putative effect on small arteries. Recently, the ethanolic extract of Eulophia macrobulbon was shown to act as a potent phosphodiesterase 5 (PDE 5) inhibitor ( Temkitthawon et al, 2017 ), an effect supported by its main compound, 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol [IC 50 = 1.7 ± 0.5 μM ( Temkitthawon et al, 2017 )].…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…Furthermore, the presence or absence of calcium‐calmodulin (Ca‐CaM) was used to examine PDE1B activity. PDE6 extracted from chicken retinas was obtained as a gift from Professor Dr Joseph A. Beavo …”

Section: Experimental and Methodsmentioning

confidence: 99%

“…The PDE5A1, PDE1B and PDE6 inhibitory activities were determined using radioassay with some modification on the methods of Sonnenburg et al . and Huang et al . The assay involves a two‐step enzymatic reaction.…”

Section: Experimental and Methodsmentioning

confidence: 99%

“…The dried micro-fractions in the 96-well plate were reconstituted with the assay buffer and sonicated for 15 min and transferred into the Eppendorf for assay. The PDE5A1, PDE1B and PDE6 inhibitory activities were determined using radioassay with some modification on the methods of Sonnenburg et al 28 and Huang et al 26,27 The assay involves a two-step enzymatic reaction. In the first step, PDE enzyme is mixed with negatively charged [ 3 H]-cGMP in the presence or absence of an inhibitor.…”

Section: Phosphodiesterase Assaymentioning

confidence: 99%

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At‐line LC‐QTOF‐MS micro‐fractionation of Derris scandens (Roxb.) Benth, coupled to radioassay for the early identification of PDE5A1 inhibitors

Bhandari¹,

Nuengchamnong

Chaichamnong

et al. 2019

Phytochemical Analysis

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Introduction Chromatographic techniques coupled with bioassays are popularly used for the detection of bioactive compounds in natural products. In this study phytochemicals responsible for showing Phosphodiesterase type 5 (PDE5) inhibitory activity in Derris scandens were studied using at‐line method. Objective The objective of this study was to develop an at‐line liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS) micro‐fractionation method for rapid separation and identification of PDE5A1 inhibitors in 95% ethanolic extract of D. scandens. Methodology Initially, the correlation between LC‐MS and PDE5A1 inhibitory activity was studied using three concentrations of 1:1 mixture of sildenafil and derrisisoflavone A; PDE5A1 inhibitors. The mixture was separated by high‐performance liquid chromatography (HPLC) column and the eluent was split into two flows in the ratio of 1:9. The major part was collected in a 96‐well plate, in each well consecutively every 30 s. The minor part was fed into an electrospray ionisation (ESI)‐QTOF‐MS system. After subsequent solvent removal, the collected micro‐fractions were subjected to radioassay to determine PDE5A1 inhibition. Results The result showed, PDE5A1 inhibitory activities of the micro‐fractions were observed in a dose response manner and found to be in agreement with an off‐line study. Similarly, 95% ethanolic extract of D. scandens was subjected to the at‐line LC‐QTOF‐MS micro‐fractionation developed, resulting in separation and tentative identification of 25 compounds with PDE5A1 inhibitory activity. Most of the compounds contained prenylated isoflavone skeleton. Additionally, the active micro‐fractions also showed selectivity on PDE5A1 over PDE6 and PDE1B. Conclusion Our results demonstrated that the at‐line coupled LC‐QTOF‐MS micro‐fractionation with PDE5A1 inhibitory assay is a valuable tool for identifying PDE5A1 inhibitors from complex extracts.

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“…Their pharmacological activities include the treatment of pulmonary, autoimmune and inflammatory diseases, cancer, and diabetes (Narkhede et al, 2016). The ethanolic extract of E. m ac r o b u l b o n c on ta i ns fl a vo no i d s , t er p e no i d s an d phosphodiesterase type 5 (PDE5) inhibitor, so it could be a pulmonary vasodilator (Temkitthawon et al, 2017). Wisutthathum et al (2018) during a study on MCT induced PH in rats, demonstrated that the treatment with ethanolic extract of E. macrobulbon inhibits CaCl 2 -induced contraction in PA rings in vitro and reduces (RV/LV+S) ratio.…”

Section: Crataegus Rhipidophylla Gandmentioning

confidence: 99%

Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension

et al. 2020

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Background: Pulmonary hypertension (PH) is a progressive disease that is associated with pulmonary arteries remodeling, right ventricle hypertrophy, right ventricular failure and finally death. The present study aims to review the medicinal plants and phytochemicals used for PH treatment in the period of 1994-2019. Methods: PubMed, Cochrane and Scopus were searched based on pulmonary hypertension, plant and phytochemical keywords from August 23, 2019. All articles that matched the study based on title and abstract were collected, non-English, repetitive and review studies were excluded. Results: Finally 41 studies remained from a total of 1290. The results show that many chemical treatments considered to this disease are ineffective in the long period because they have a controlling role, not a therapeutic one. On the other hand, plants and phytochemicals could be more effective due to their action on many mechanisms that cause the progression of PH. Conclusion: Studies have shown that herbs and phytochemicals used to treat PH do their effects from six mechanisms. These mechanisms include antiproliferative, antioxidant, antivascular remodeling, anti-inflammatory, vasodilatory and apoptosis inducing actions. According to the present study, many of these medicinal plants and phytochemicals can have effects that are more therapeutic than chemical drugs if used appropriately.

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Phenanthrenes from Eulophia macrobulbon as Novel Phosphodiesterase-5 Inhibitors

Cited by 15 publications

References 26 publications

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

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

At‐line LC‐QTOF‐MS micro‐fractionation of Derris scandens (Roxb.) Benth, coupled to radioassay for the early identification of PDE5A1 inhibitors

Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension

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