Papers by Prapapan Temkitthawon
Phytomedicine, Nov 1, 2018
Eulophia macrobulbon extract relaxes rat isolated pulmonary artery and protects against monocrota... more Eulophia macrobulbon extract relaxes rat isolated pulmonary artery and protects against monocrotaline-induced pulmonary arterial hypertension,
Social Science Research Network, 2022
The open conference proceedings journal, Mar 1, 2013
Kaempferia parviflora Wall. ex Baker has been popularly used as male sexual performance enhancer ... more Kaempferia parviflora Wall. ex Baker has been popularly used as male sexual performance enhancer in Thailand. However, its mechanisms were still unknown. One of the possible mechanism for this remedy is phosphodiesterase 5 (PDE5) inhibition. Among 41 plant extracts, the rhizomes of K. parviflora ethanolic extract could inhibit PDE5 at 50 µg/ml. Therefore, eight 7methoxyflavones which are the major the chemical constituents isolated from rhizomes of K. parviflora were further investigated on inhibitory activity against PDE5. Moreover, the selectivity of these compounds on PDE5 over PDE6 was evaluated. The results showed that 7-methoxyflavones from this plant showed inhibition effect toward both enzymes. The most potent PDE5 inhibitor was 5,7-dimethoxyflavone (IC 50 =10.64±2.09 µM, selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition. K. parviflora rhizome extract and its 7-methoxyflavone constituents had moderate inhibitory activity against PDE5. This finding provides an explanation for enhancing sexual performance in the traditional use of K. parviflora. Moreover, 5,7dimethoxyflavones could be a useful lead compound for clinically efficacious PDE5 inhibitors.
Planta Medica, Aug 24, 2006
The open conference proceedings journal, Mar 1, 2013
Kaempferia parviflora Wall. ex Baker has been popularly used as male sexual performance enhancer ... more Kaempferia parviflora Wall. ex Baker has been popularly used as male sexual performance enhancer in Thailand. However, its mechanisms were still unknown. One of the possible mechanism for this remedy is phosphodiesterase 5 (PDE5) inhibition. Among 41 plant extracts, the rhizomes of K. parviflora ethanolic extract could inhibit PDE5 at 50 µg/ml. Therefore, eight 7methoxyflavones which are the major the chemical constituents isolated from rhizomes of K. parviflora were further investigated on inhibitory activity against PDE5. Moreover, the selectivity of these compounds on PDE5 over PDE6 was evaluated. The results showed that 7-methoxyflavones from this plant showed inhibition effect toward both enzymes. The most potent PDE5 inhibitor was 5,7-dimethoxyflavone (IC 50 =10.64±2.09 µM, selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition. K. parviflora rhizome extract and its 7-methoxyflavone constituents had moderate inhibitory activity against PDE5. This finding provides an explanation for enhancing sexual performance in the traditional use of K. parviflora. Moreover, 5,7dimethoxyflavones could be a useful lead compound for clinically efficacious PDE5 inhibitors.
The open conference proceedings journal, Mar 1, 2013
Erectile Dysfunction (ED) is a common public health problem affecting millions of men worldwide. ... more Erectile Dysfunction (ED) is a common public health problem affecting millions of men worldwide. Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of ED. However, most of PDE5 inhibitors show some undesirable side effects. The aim of the study is to search for new PDE5 inhibitors from synthesis and natural sources. In our preliminary screening, we found that curcumin, a major component in Curcuma longa L., together with its analogues showed inhibition effect on PDE5. Interestingly, some analogs showed no effect on PDE6 which is the isozyme that can be found in rod and cone cells within the eye. The IC 50 value of curcumin analogue, ASKI087 against PDE5 was in a micromolar range. The curcuminoid structure could be a promising lead for PDE5 inhibitors.
Natural Product Communications, Feb 1, 2015
Five flavonoids, one isoflavone and five xanthones were isolated from Anaxagorea luzonensis. Of t... more Five flavonoids, one isoflavone and five xanthones were isolated from Anaxagorea luzonensis. Of these eleven isolated compounds, 1,3,5-trihydroxy-4prenylxanthone (3) was a relatively potent inhibitor of phosphodiesterase type 5 (PDE5), with an IC 50 value of 3.0 µM. This is the first report showing that natural xanthones can exhibit promising PDE5 inhibitory activity. Moreover, this study revealed that the presence of the C-4 prenyl residue attached to the xanthone core is correlated with the significant PDE5 inhibitory activity.
Natural Product Communications, 2017
Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of erectile dysfunction and p... more Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of erectile dysfunction and pulmonary hypertension. In order to search for new leads of PDE5 inhibitors, we investigated the chemical constituents of the tubers of Eulophia macrobulbon (E.C. Parish & Rchb. f.) Hook. f. A new phenanthrene, 9,10-dihydro-4-(4-hydroxybenzyl)-2,5-dimethoxyphenanthrene-1,7-diol (1) and three known phenanthrenes i.e., 1-(4-hydroxybenzyl)-4,8dimethoxyphenanthrene-2,7-diol (2), (9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol (3) and 1,5,7-trimethoxyphenanthrene-2,6-diol) (4) were isolated. Among these, 2 was the most potent PDE5 inhibitor (IC 50 =1.67±0.54 µM) evaluated by the [ 3 H]cGMP radioassay method, whereas 1 showed mild activity (IC 50 = 62.3±3.3 µM). Their inhibitory selectivities against PDE5 over PDE6 were also studied. This study suggests phenanthrenes as a new class of PDE5 inhibitors.
Planta Medica, Apr 27, 2018
Phosphodiesterase 5 inhibitors have been used as a first-line medicine for the treatment of erect... more Phosphodiesterase 5 inhibitors have been used as a first-line medicine for the treatment of erectile dysfunction. In the search for new phosphodiesterase 5 inhibitors from natural sources, we found that the 95% ethanol extract of Derris scandens stem showed phosphodiesterase 5 inhibitory activity with an IC50 value of about 7 µg/mL. Seven isoflavones and a coumarin constituent isolated from this plant were investigated for phosphodiesterase 5 inhibitory activity. The results showed that osajin (8), 4′,5,7-trihydroxybiprenylisoflavone (4), and derrisisoflavone A (2) had the ability to inhibit phosphodiesterase 5 with IC50 values of 4, 8, and 9 µM, respectively. These compounds exhibited selectivity on phosphodiesterase 5 over phosphodiesterase 1, however, the selectivity on phosphodiesterase 5 over phosphodiesterase 6 was low. In order to quantitatively determine these bioactive constituents in D. scandens extract, LC-QTOF-MS method has been developed and validated. The limit of quantitation values in the range of 0.1 – 5 µg/mL were obtained. The assay showed satisfactory precision and accuracy. The results from our method showed that the 95% ethanol extract of D. scandens stem was comprised of all eight compounds, with derrisisoflavone A (2) and lupalbigenin (3) presenting as the major constituents.
The open conference proceedings journal, Mar 1, 2013
The role of deformable liposomes characteristics on skin permeability has evoked considerable int... more The role of deformable liposomes characteristics on skin permeability has evoked considerable interest, since the articles reporting the effectiveness of transfersomes for skin delivery were increasingly published. Several reports focus on the effect of formulation factor which directly affected the transfersome's skin permeability. However, the effect of formulation factors was not fully understood as the contradictory results. To clarify this problem, the reliable statistical techniques, excellent experimental design and systematical variation were used in this study. Transfersomes loaded meloxicam containing controlled amount of phosphatidylcholine (PC), cholesterol (Chol), type of surfactant (hydrophilic part, lipophilic part) were prepared and investigated for the physicochemical characteristics (e.g., size, size distribution, charge, elasticity, drug content, morphology) and skin permeability. The results indicated that the transfersome containing 10% cholesterol, 29% cetylpyridinium chloride (cationic surfactant) with 16 carbons chain length and 10% meloxicam was the optimal formulation for meloxicam transdermal delivery carrier. The skin permeation of meloxicam in novel transfersome formulation was higher than classical transfersomes, conventional liposomes and meloxicam saturated suspension. Thus, our finding provided important fundamental information for developing novel deformable liposomes for transdermal drug delivery, especially transfersomes containing surfactant systems.
Fitoterapia, Oct 1, 2019
Three new compounds including two depsidones (simplicildones J and K) and one dihydroxanthenone (... more Three new compounds including two depsidones (simplicildones J and K) and one dihydroxanthenone (globosuxanthone E) together with nine known compounds were obtained from the crude extracts of two endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 which were isolated from the leaves of Hevea brasiliensis. The structures were elucidated by spectroscopic evidence. The absolute configuration of globosuxanthone E was established by means of experimental and calculated TDDFT ECD data. Simplicildone K exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 128 μg/mL. Simplicildone K and globosuxanthone E displayed antifungal activity against Cryptococcus neoformans ATCC90113 with the same MIC values of 32 μg/mL. In addition, known botryohordine C and simplicildone A showed phosphodiesterase 5 inhibitory activity with the IC 50 values of 5.69 and 9.96 μM, respectively, and were noncytotoxic toward noncancerous Vero cells.
Journal of Pharmacy and Pharmacology, Sep 1, 2014
Objectives Phosphodiesterase (PDE)-5 inhibitors are useful as vasodilators for the treatment of p... more Objectives Phosphodiesterase (PDE)-5 inhibitors are useful as vasodilators for the treatment of pulmonary arterial hypertension. We aimed to study curcumin analogues for PDE5 inhibitory activity and vasorelaxation of rat pulmonary arteries. Methods Three natural curcuminoids (1-3) and six synthetic analogues (4-9) were tested for PDE5 and PDE6 inhibitory activities using enzymatic radioassay. Their vasorelaxation was measured using freshly isolated segments of rat pulmonary artery and aorta. Key findings Curcuminoids (1-3) mildly inhibited PDE5 (half maximal inhibitory concentration (IC 50) = 18 µm): the metamethoxyl of curcumin was important for PDE5 inhibition. But hydroxyl rearrangements, removing both methoxyls and one ketomethylene, yielded the potent 7 and 9 (IC 50 = 4 µm) (compared with sildenafil, IC50 = 0.03 µm). Only 1, 3 and 4 were PDE5 selective over PDE6. Triazole-carboxylic addition provided water-solubility while preserving potency. All analogues possessed concentration-dependent vasorelaxant activity on pulmonary arteries (40% of maximal effective concentration (EC 40) = 29-90 µm, maximum response = 60-90% at 300 µm), while compounds (1-8) were weakly acting in aorta (maximum response <40%). Only demethoxycurcumin (2) and analogues 5, 8, 9 had endothelium-dependent actions. Sildenafil was highly potent (EC 40 = 0.04 µm) and highly endothelium dependent in pulmonary artery but weak on intact aorta (EC40 = 1.8 µm). Activity profiles suggest actions through additional cell pathways for promoting vasorelaxation. Conclusions Curcumin analogues are potential leads for developing efficacious and selective PDE5 inhibitors and other pathologies of pulmonary hypertension.
Journal of Ethnopharmacology, Oct 1, 2011
Aim of the study-A number of medicinal plants are used in traditional medicine to treat erectile ... more Aim of the study-A number of medicinal plants are used in traditional medicine to treat erectile dysfunction. Since cyclic nucleotide PDEs inhibitors underlie several current treatments for this condition, we sought to show whether these plants might contain substantial amounts of PDE5 inhibitors. Materials and methods-Forty one plant extracts and eight 7-methoxyflavones from Kaempferia parviflora Wall. ex Baker were screened for PDE5 and PDE6 inhibitory activities using the two-step radioactive assay. The PDE5 and PDE6 were prepared from mice lung and chicken retinas, respectively. All plant extracts were tested at 50 μg/ml whereas the pure compounds were tested at 10 μM. Results-From forty one plant extracts tested, four showed the PDE5 inhibitory effect. The chemical constituents isolated from rhizomes of Kaempferia parviflora were further investigated on inhibitory activity against PDE5 and PDE6. The results showed that 7-methoxyflavones from this plant showed inhibition toward both enzymes. The most potent PDE5 inhibitor was 5,7dimethoxyflavone (IC 50 = 10.64 ± 2.09 μM, selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition.
Journal of Ethnopharmacology, Dec 1, 2003
Acetylcholinesterase (AChE) inhibitor has been used as a drug for the symptomatic treatment of Al... more Acetylcholinesterase (AChE) inhibitor has been used as a drug for the symptomatic treatment of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. In order to search for new AChE inhibitors, 32 plants used in Thai traditional rejuvenating and neurotonic remedies were collected. The plant methanolic extracts were tested for AChE inhibitory activity using Ellman&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s colorimetric method in 96-welled microplates. The results showed that the methanolic extracts from roots of Stephania suberosa Forman. and Tabernaemontana divaricata (L.) R.Br. ex Roem. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Schult. at concentration of 0.1 mg/ml inhibited more than 90% of AChE activity. At the same concentration, four extracts, i.e. stems of Piper interruptum Opiz., seeds of Piper nigrum L., rootbarks of Butea superba Roxb. and roots of Cassia fistula L. extracts showed 50-65% inhibitory activity on AChE. The rest of the extracts showed the AChE inhibitory activity below 50%.
Molecules, Jan 14, 2019
Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etio... more Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etiologies and pathogenesis. PAH decreases life expectancy due to pulmonary vascular remodeling, elevation of mean pulmonary arterial pressure, and ultimately progresses to heart failure. While clinical treatments are available to reduce the associated symptoms, a complete cure has yet to be found. Phosphodiesterase-5 (PDE-5) inhibition has been identified as a possible intervention point in PAH treatment. The functional vasodilation response to N 2 ,N 4-diamino quinazoline analogues with differing PDE-5 inhibitory activities and varying physicochemical properties were assessed in both endothelium-intact and denuded rat pulmonary arteries to gain greater insight into their mode of action. All analogues produced vasorelaxant effects with EC50s ranging from 0.58 ± 0.22 µM to >30 µM. It was observed that vasodilation response in intact vessels was highly correlated with that of denuded vessels. The~10% drop in activity is consistent with a loss of the nitric oxide mediated cyclic guanosine monophosphate (NO/cGMP) pathway in the latter case. A moderate correlation between the vasodilation response and PDE-5 inhibitory activity in the intact vessels was observed. Experimental protocol using the alpha-adrenergic (α 1) receptor agonist, phenylephrine (PE), was undertaken to assess whether quinazoline derivatives showed competitive behavior similar to the α 1 receptor blocker, prazosin, itself a quinazoline derivative, or to the PDE-5 inhibitor, sildenafil. Competitive experiments with the α 1-adrenergic receptor agonist point to quinazoline derivatives under investigation here act via PDE-5 inhibition and not the former. The pre-incubation of pulmonary arterial rings with quinazoline test compounds (10 µM) reduced the contractile response to PE around 40-60%. The most promising compound (9) possessed~32 folds higher
Frontiers in Pharmacology, May 22, 2018
Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat... more 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), 4aminopyridine 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 Ca 2+-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca 2+ 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 K Ca channels, inhibition of Ca 2+ channels, inhibition of intracellular Ca 2+ release and PDE inhibition).
Molecules, Aug 17, 2019
A major goal in the discovery of bioactive natural products is to rapidly identify active compoun... more A major goal in the discovery of bioactive natural products is to rapidly identify active compound(s) and dereplicate known molecules from complex biological extracts. The conventional bioassay-guided fractionation process can be time consuming and often requires multi-step procedures. Herein, we apply a metabolomic strategy merging multivariate data analysis and multi-informative molecular maps to rapidly prioritize bioactive molecules directly from crude plant extracts. The strategy was applied to 59 extracts of three Bacopa species (B. monnieri, B. caroliniana and B. floribunda), which were profiled by UHPLC-HRMS 2 and screened for anti-lipid peroxidation activity. Using this approach, six lipid peroxidation inhibitors 1-6 of three Bacopa spp. were discovered, three of them being new compounds: monnieraside IV (4), monnieraside V (5) and monnieraside VI (6). The results demonstrate that this combined approach could efficiently guide the discovery of new bioactive natural products. Furthermore, the approach allowed to evidence that main semi-quantitative changes in composition linked to the anti-lipid peroxidation activity were also correlated to seasonal effects notably for B. monnieri.
RSC Advances
A facile and green one-pot synthesis of AChE quinazolinone inhibitors was developed using microwa... more A facile and green one-pot synthesis of AChE quinazolinone inhibitors was developed using microwave irradiation under solvent free conditions.
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Papers by Prapapan Temkitthawon