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1.
Fitoterapia ; 138: 104299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404616

RESUMO

Gerbera piloselloides (L.) Cass. (Compositae) possesses various biological effects. It is used as an oriental remedy for relieving cough and resolving phlegm. The present study is to investigate the vasodilation effects of Gerbera piloselloides on isolated rat mesenteric arteries (MAs) and the potential mechanism. Different organic extracts of Gerbera piloselloides were tested, and an HPLC-UV-FD-based analytical method was established to identify the active constituents. The principal components, namely, 8-MOP (8-methoxypsoralan) and 8-MSD (8-methoxysmyrindiol), were found to be predominant in the extracts of petroleum ether and dichloroform, which showed stronger vasodilation activities. 8-MSD was isolated from Gerbera piloselloides by silica gel column chromatography coupled with a Waters 2545 high throughput autopurification system, and its vasodilation effects were explored by an assay of tension on rat MA rings. The results suggest that 8-MSD induces vascular relaxation in rat MAs via an endothelium-dependent mechanism involving the Kir channel, which enables Ca2+ entry in the cell and activates production of NO. The present research indicates that 8-MSD may be therapeutically useful as an anti-hypertension agent and to potentially treat cardiovascular and gastrointestinal diseases.


Assuntos
Asteraceae/química , Artérias Mesentéricas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação , Vasodilatadores/farmacologia , Animais , China , Endotélio Vascular/efeitos dos fármacos , Feminino , Técnicas In Vitro , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Vasodilatadores/isolamento & purificação
2.
Chem Pharm Bull (Tokyo) ; 67(7): 675-689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257323

RESUMO

An Orobanchaceae plant Cistanche tubulosa (SCHENK) WIGHT (Kanka-nikujuyou in Japanese), which is one of the authorized plant resources as Cistanches Herba in both Japanese and Chinese Pharmacopoeias, is a perennial parasitic plant growing on roots of sand-fixing plants. The stems of C. tubulosa have traditionally been used for treatment of impotence, sterility, lumbago, and body weakness as well as a promoting agent of blood circulation. In recent years, Cistanches Herba has also been widely used as a health food supplement in Japan, China, and Southeast Asian countries. Here we review our recent studies on chemical constituents from the stems of C. tubulosa as well as their bioactivities such as vasorelaxtant, hepatoprotective, and glucose tolerance improving effects.


Assuntos
Produtos Biológicos/química , Cistanche/química , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Cistanche/metabolismo , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Caules de Planta/química , Caules de Planta/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia
3.
Anal Bioanal Chem ; 411(15): 3281-3290, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989270

RESUMO

Quantification of ultra-trace analytes in complex biological samples using micro-solid-phase extraction followed by direct detection with internal extractive electrospray ionization mass spectrometry (µSPE-iEESI-MS) was demonstrated. 1-Hydroxypyrene (1-OHP) and papaverine at attomole levels in human raw urine samples were analyzed under negative and positive ion detection mode, respectively. The µSPE was simply prepared by packing a disposable syringe filter with octadecyl carbon chain (C18)-bonded micro silica particles, which were then treated as the "bulk sample" after the analytes were efficiently enriched by the C18 particles. Under the optimized experimental conditions, the analytes were readily eluted by isopropanol/water (80/20, V/V) at a high voltage of ± 4.0 kV, producing analyte ions under ambient conditions. The limit of detection (LOD) was 0.02 pg/L (9.2 amol) for 1-hydroxypyrene and 0.02 pg/L (5.9 amol) for papaverine. The acceptable linearity (R2 > 0.99), signal stability (RSD ≤ 10.7%), spike recoveries (91-95%), and comparable results for real urine samples were also achieved, opening up possibilities for quantitative analysis of trace compounds (at attomole levels) in complex bio-samples. Graphical abstract.


Assuntos
Papaverina/urina , Pirenos/urina , Microextração em Fase Sólida/instrumentação , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Vasodilatadores/urina , Adsorção , Biomarcadores/urina , Desenho de Equipamento , Humanos , Limite de Detecção , Papaverina/isolamento & purificação , Pirenos/isolamento & purificação , Reprodutibilidade dos Testes , Microextração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodos , Vasodilatadores/isolamento & purificação
4.
Org Lett ; 21(4): 1197-1201, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30702896

RESUMO

Two novel sesquiterpenoids, curcumanes A (1) and B (2), possessing unprecedented skeletons with a dicyclo[3.2.1]octane and a dicyclo[3.3.1]nonane moiety, respectively, were isolated from Curcuma longa. Both of them had remarkable vasorelaxant activity on rat aorta via blocking extracellular Ca2+ influx through VDCCs and ROCCs. The activity of 1 was endothelium-independent, while that of 2 was endothelium-dependent. Compound 2 also prolonged APTT and TT to inhibit blood coagulation.


Assuntos
Aorta Torácica/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Curcuma/química , Receptores de Detecção de Cálcio/antagonistas & inibidores , Vasodilatadores/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Ratos , Receptores de Detecção de Cálcio/metabolismo , Vasodilatadores/química , Vasodilatadores/isolamento & purificação
5.
Phytomedicine ; 53: 163-170, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668395

RESUMO

BACKGROUND: Zanthoxylum armatum DC (Z. armatum), belonging to Rutaceae family, has been traditionally used for the treatment of various diseases such as hypertension, abdominal pain, headache, fever, high altitude sickness, diarrhea, dysentery, and as a tonic, condiment, and an anthelmintic treatment. HYPOTHESIS: The present study aims to evaluate the vasorelaxant effect of a methanolic extract of the fruits of Z. armatum, isolate the active components and characterize the underlying mechanism. STUDY DESIGN: A methanolic extract of fruits of Z. armatum was prepared and its vasorelaxant effect was studied using porcine coronary artery rings. Thereafter, the methanolic extract was analyzed, and a major compound was isolated and its structure elucidated (tambulin). Different pharmacological tools were used to characterize the vasorelaxant effect of tambulin. RESULTS: The methanolic extract and the isolated tambulin caused similar endothelium-independent relaxations of porcine coronary artery rings with and without endothelium indicating a direct relaxing effect at the vascular smooth muscle. Tambulin did not affect the relaxation curves to the endothelium-dependent vasodilators, bradykinin and the calcium ionophore A23187 in rings with endothelium. Tambulin (1 µM) slightly but significantly shifted leftwards the concentration-relaxation curve to the endothelium-independent vasodilators, sodium nitroprusside (SNP), forskolin (FC) and isoproterenol but not those to soluble guanylyl cyclase activators (YC-1 and BAY 41-2272) and K+ channel openers (levcromakalim and 1-EBIO). Pretreatment with tambulin inhibited, in a concentration-dependent manner, contractions to KCl, serotonin (5-HT), CaCl2 and U46619 in coronary artery rings without endothelium. Both the protein kinase A (H-89, 10 µM) and the protein kinase G (Rp-8-br-cyclic GMPS, 30 µM) inhibitors significantly reduced relaxations to tambulin in coronary artery rings without endothelium. CONCLUSION: The present findings indicate that tambulin isolated from Z. armatum (fruits) is a major active principle inducing vasorelaxation through a direct effect at the vascular smooth muscle and involving both the cyclic AMP and/or cyclic GMP relaxing pathways.


Assuntos
Benzopiranos/farmacologia , Vasos Coronários/efeitos dos fármacos , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Vasodilatadores/farmacologia , Zanthoxylum/química , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Benzopiranos/química , Bradicinina/farmacologia , Vasos Coronários/metabolismo , Vasos Coronários/fisiologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Frutas/química , Metanol/química , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Suínos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/química , Vasodilatadores/isolamento & purificação
6.
J Agric Food Chem ; 67(5): 1437-1442, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30609899

RESUMO

We recently identified a novel, potent antihypertensive peptide, Leu-Arg-Ala (LRA; minimum effective dose = 0.25 mg/kg), from rice bran protein. In this study, we found that LRA potently relaxed mesenteric arteries isolated from spontaneously hypertensive rats (SHRs) (EC50 = 0.1 µM). In contrast, the vasorelaxant activity of each amino acid that constitutes the LRA tripeptide was remarkably attenuated. The LRA-induced vasorelaxant activity was inhibited by N(G)-nitro-l-arginine methyl ester (L-NAME; NO synthase [NOS] inhibitor) but not by an antagonist of bradykinin B2 and Mas receptors or by a phosphoinositide 3-kinase inhibitor. The antihypertensive effect induced after the oral administration of LRA was inhibited by L-NAME. LRA also induced the phosphorylation of endothelial NOS in human umbilical vein endothelial cells. Taken together, LRA may exhibit antihypertensive effects via NO-mediated vasorelaxation. LRA is the first example of a NO-dependent vasorelaxant peptide identified from rice bran protein.


Assuntos
Anti-Hipertensivos/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Óxido Nítrico/metabolismo , Oligopeptídeos/administração & dosagem , Oryza/química , Extratos Vegetais/administração & dosagem , Vasodilatadores/administração & dosagem , Animais , Anti-Hipertensivos/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Oligopeptídeos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Endogâmicos SHR , Sementes/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/isolamento & purificação
7.
Eur J Mass Spectrom (Chichester) ; 25(4): 372-380, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30526026

RESUMO

A method for bioanalysis of pentoxifylline in human plasma was developed using liquid chromatography-tandem mass spectrometry, which is simple, specific, and sensitive. Pentoxifylline D5 was used as the internal standard. Employing only 100 µl of human plasma, processing was done with solid-phase extraction technique. The analyte and the internal standard were separated from endogenous components on Ace phenyl column using a mixture of 5 mM ammonium acetate buffer and high performance liquid chromatography grade acetonitrile (60:40, v/v) as mobile phase at a flow rate of 1 ml/min. The linearity of the method was in the range of 3-1200 ng/ml with r2 > 0.99. Positive ion MRM mode was used for the detection of the analyte and the internal standard. The method was validated as per the US Food and Drug Administration guidelines and the results were within the acceptance limits. The proposed method was applied for comparative pharmacokinetic study of pentoxifylline after oral administration of 400 and 600 mg tablets to South Indian male subjects under fed conditions.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Pentoxifilina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Vasodilatadores/farmacocinética , Humanos , Masculino , Pentoxifilina/sangue , Pentoxifilina/isolamento & purificação , Sensibilidade e Especificidade , Extração em Fase Sólida , Vasodilatadores/sangue , Vasodilatadores/isolamento & purificação
8.
Fitoterapia ; 131: 182-188, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30339926

RESUMO

Secondary metabolites from lichens are known for exhibiting various biological effects such as anti-inflammatory, antioxidant and antibacterial activities. Despite this wide range of reported biological effects, their impact on the formation of advanced glycation end products (AGEs) remains vastly unexplored. The latter are known contributors to lifestyle and age-related diseases such as Alzheimer and Parkinson. Moreover, the development of atherosclerosis and arterial stiffness is causally linked to the formation of AGEs. With this in mind, the present work evaluated the inhibitory effects of secondary lichen metabolites on the formation of pentosidine-like AGEs' by using an in vitro, Maillard reaction based, fluorescence assay. Overall, thirty-seven natural and five synthetically modified compounds were tested, eighteen of which exhibiting IC50 values in the range of 0.05 to 0.70 mM. This corresponds to 2 to 32 fold of the inhibitory activity of aminoguanidine. Targeting one major inhibiting mechanism of AGEs formation, all compounds were additionally evaluated on their radical scavenging capacities in an DPPH assay. Furthermore, as both AGEs' formation and hypertension are major risk factors for atherosclerosis, compounds that were available in sufficient amounts were also tested for their vasodilative effects. Overall, and though some of the active compounds were previously reported cytotoxic, present results highlight the interesting potential of secondary lichen metabolites as anti-AGEs and vasodilative agents.


Assuntos
Produtos Biológicos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Líquens/química , Vasodilatadores/farmacologia , Animais , Produtos Biológicos/isolamento & purificação , Masculino , Estrutura Molecular , Ratos Endogâmicos WKY , Metabolismo Secundário , Vasodilatadores/isolamento & purificação
9.
Bioorg Med Chem ; 26(14): 4320-4328, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30049584

RESUMO

Four new diterpenoids scapanacins A-D (1-4) including one kaurane and three clerodane derivatives, along with eleven known compounds (9-15), were isolated from the Chinese liverwort Scapania carinthiaca J.B. Jack ex Lindb. Their structures were determined based on extensive spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Vasorelaxant activity assays of the clerodane-type diterpenoids 2, and 4-8 revealed that they relaxed 3rd-order rat mesenteric arterioles pre-contracted with norepinephrine (NE). Further assays with scapanacin D (4) confirmed that the vasodilatation was mediated through inhibition of Ca2+ influx via voltage-dependent Ca2+ channels (VDCs), and this Ca2+ channel blocking effect was also confirmed by inhibiting the extracellular Ca2+ influx in MOVAS cells. Besides, very little decrease of the relaxant activity caused by 4 on endothelium-denuded mesenteric arterioles with NE also suggested the vasodilatation was mainly produced by inhibiting Ca2+-induced contraction of smooth muscle. In addition, cytotoxicity testing showed that compounds 1 and 9 with α,ß-unsaturated ketone exhibited inhibitory activities against a small panel of human cancer cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Hepatófitas/química , Terpenos/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação , Vasodilatadores/química , Vasodilatadores/isolamento & purificação
10.
Molecules ; 23(6)2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29912156

RESUMO

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4'-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4'-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4'-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.


Assuntos
Músculo Liso/irrigação sanguínea , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , GMP Cíclico/metabolismo , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Medicina Tradicional , México , Estrutura Molecular , Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Ratos , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Vasodilatação , Vasodilatadores/química
11.
Pharm Biol ; 56(1): 225-234, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29560776

RESUMO

CONTEXT: Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. OBJECTIVE: The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. MATERIALS AND METHODS: Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. RESULTS: In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K+-(80 mM), Ra.Cr induced vasorelaxation and shifted Ca2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca2+-free medium. DISCUSSION AND CONCLUSIONS: The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.


Assuntos
Anti-Hipertensivos/farmacologia , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Rumex , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , Aorta Torácica/metabolismo , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Metanol/química , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Prostaglandina-Endoperóxido Sintases/metabolismo , Coelhos , Ratos Sprague-Dawley , Rumex/química , Solventes/química , Vasodilatadores/isolamento & purificação
12.
Pak J Pharm Sci ; 31(1): 95-102, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29348090

RESUMO

In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate the sound mechanistic background in the treatment of gastrointestinal, bronchial and vascular disorders as well as in pain, emesis, pyrexia and bacterial infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr) exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with Cr. Cr caused the rightward shift of calcium concentration response curves, similar to verapamil. Cr. Cr also caused the relaxation of K+(80 mM)- and carbachol (1 µM)-induced contractions of trachea preparations, similar to that of verapamil. Moreover, Cr. Cr also relaxed the contraction induced by the K+ (80 mM) and phenylephrine (1 µM) of aorta preparations. Data show that C. rotundus possess the spasmolytic, bronchodilator and vasodilator activities possibly through calcium channels blockade; validating its folkloric use in diarrhea, dyspepsia, bronchitis, asthma and hypertension in addition to antibacterial, antiemetic, antipyretic and analgesic activities.


Assuntos
Broncodilatadores/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cyperus/química , Medicina Tradicional/métodos , Extratos Vegetais/farmacologia , Vasodilatadores/farmacologia , Animais , Broncodilatadores/isolamento & purificação , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Galinhas , Feminino , Técnicas In Vitro , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Coelhos , Vasodilatadores/isolamento & purificação
13.
Chem Biodivers ; 14(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29139211

RESUMO

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.


Assuntos
Alisma/química , Terpenos/química , 11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Alisma/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Extratos Vegetais/química , Cloreto de Potássio/toxicidade , Ratos , Rizoma/química , Rizoma/metabolismo , Terpenos/metabolismo , Terpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Difração de Raios X
14.
Pharm Biol ; 55(1): 2083-2094, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28832263

RESUMO

CONTEXT: Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia. OBJECTIVE: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint. MATERIALS AND METHODS: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists. RESULTS: The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC50 0.971 ± 0.459 mg/mL), methylene blue (EC50 1.203 ± 0.426 mg/mL), indomethacin (EC50 2.128 ± 1.218 mg/mL), atropine (EC50 0.470 ± 0.325 mg/mL), and propranolol (EC50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca2+ released from the sarcoplasmic reticulum and blocking calcium channels. CONCLUSIONS: The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI2 signalling pathways, and modulation of calcium/potassium channels, and muscarinic and ß2-adrenergic receptor levels.


Assuntos
Aorta Torácica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Vernonia , Animais , Aorta Torácica/fisiologia , Relação Dose-Resposta a Droga , Etanol/farmacologia , Masculino , Técnicas de Cultura de Órgãos , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Ratos , Ratos Sprague-Dawley , Vasodilatação/fisiologia , Vasodilatadores/isolamento & purificação
15.
Fitoterapia ; 120: 67-71, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28576720

RESUMO

Pocahemiketals A and B (1 and 2), two novel hemiketal sesquiterpenoids with unprecedented skeletons, were isolated from the essential oil of the aerial parts of Pogostemon cablin. In addition to a bicyclo[3.2.1]-carbon core, 1 and 2 possessed a hemiketal α,ß-unsaturated-γ-lactone moiety. Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculation, and single-crystal X-ray diffraction. Compound 2 exhibited significant vasorelaxant activity against phenylephrine-induced contraction of a rat aorta ring with the EC50 value of 16.32µM.


Assuntos
Aorta/efeitos dos fármacos , Óleos Voláteis/química , Pogostemon/química , Sesquiterpenos/farmacologia , Vasodilatadores/farmacologia , Animais , Técnicas In Vitro , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química , Ratos , Sesquiterpenos/isolamento & purificação , Vasodilatadores/isolamento & purificação
16.
Molecules ; 22(6)2017 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-28561785

RESUMO

Dodoneine (Ddn) is one of the active compounds identified from Agelanthusdodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine's vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.


Assuntos
Anti-Hipertensivos/química , Aorta/efeitos dos fármacos , Inibidores da Anidrase Carbônica/química , Hipertensão/tratamento farmacológico , Loranthaceae/química , Fenóis/química , Pironas/química , Vasodilatadores/química , Animais , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , Aorta/metabolismo , Aorta/fisiopatologia , Produtos Biológicos , Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Anidrase Carbônica III/metabolismo , Inibidores da Anidrase Carbônica/isolamento & purificação , Inibidores da Anidrase Carbônica/farmacologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Fenóis/isolamento & purificação , Fenóis/farmacologia , Plantas Medicinais/química , Pironas/isolamento & purificação , Pironas/farmacologia , Ratos , Técnicas de Cultura de Tecidos , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia
17.
Pak J Pharm Sci ; 30(1): 199-203, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28603132

RESUMO

The aim of this experimental work was to explore the potential pharmacological activities of Gaultheria trichophylla Royle in hyperactive respiratory and vascular conditions. Gaultheria trichophylla was extracted with solvents, phytochemical detection tests were performed, and rabbit trachea and aorta strips were used to evaluate its effects on airways and vascular smooth muscles. Qualitative phytochemical tests showed the presence of flavonoids, alkaloids, anthraquinones, saponins, terpenoids, and condensed tannins. The methanol extract caused inhibition (EC50 values of 3.12 mg/mL) of carbachol (1 µM) and partial relaxation of K+(80 mM) caused contractions in tracheal strips. The chloroform extract was comparatively more potent against carbachol than K+ induced contraction with EC50 values of 0.64 and 2.26 mg/mL, respectively. However, the n-hexane extract showed more potency against K+ than cabachol induced contractions, as in case with verapamil, with EC50 values of 0.61 and 6.58 mg/mL, respectively. In isolated prepared trachea, the extracts displaced the carbachol concentration response curves and maximum response was suppressed. In rabbit aorta preparations, methanol and n-hexane extracts partially relaxed phenylephrine (1 µM) and K+ induced vasoconstrictions. However, the chloroform extract inhibited phenylephrine induced contractions and exhibited a vasoconstrictor effect at lower concentrations and a relaxant effect at higher concentrations against K+ precontractions. The data indicates that, in addition to others, the extracts of G .trichophylla possess verapamil like Ca++ channel blocking components which explain the possible role of this plant in respiratory and vascular conditions.


Assuntos
Broncoconstrição/efeitos dos fármacos , Broncodilatadores/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Gaultheria/química , Músculo Liso Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Traqueia/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Broncodilatadores/isolamento & purificação , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Clorofórmio/química , Relação Dose-Resposta a Droga , Feminino , Hexanos/química , Técnicas In Vitro , Masculino , Metanol/química , Músculo Liso Vascular/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Coelhos , Solventes/química , Traqueia/metabolismo , Vasodilatadores/isolamento & purificação , Verapamil/farmacologia
18.
Bioorg Med Chem Lett ; 27(10): 2124-2128, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28389148

RESUMO

Vasorelaxation activity guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of 6 chromanones (calofolic acids A-F, 1-6). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination of CD spectroscopy and DFT calculation. All isolated chromanones showed dose-dependent vasorelaxation activity on isolated rat aorta.


Assuntos
Calophyllum/química , Cromonas/química , Vasodilatadores/química , Animais , Aorta/efeitos dos fármacos , Calophyllum/metabolismo , Cromonas/isolamento & purificação , Cromonas/farmacologia , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Conformação Molecular , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química , Ratos , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia
19.
Mol Med Rep ; 15(5): 3143-3146, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28350093

RESUMO

The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti­vasoconstrictive effect of AG may be effective in the treatment of abnormal cold­mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold­exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37˚C) or cold (25˚C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin­1 (ET­1)­mediated RhoA activation in pericytes; however, cold­induced ET­1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold­induced phosphorylation of focal adhesion kinase, proto­oncogene tyrosine­protein kinase Src and extracellular signal­related kinase. Therefore, AG treatment demonstrated an ability to reduce cold­induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET­1­mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.


Assuntos
Angelica/química , Extratos Vegetais/química , Proteína rhoA de Ligação ao GTP/metabolismo , Angelica/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Endotelina-1/análise , Endotelina-1/metabolismo , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Microscopia Confocal , Pericitos/citologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Temperatura Ambiente , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Quinases da Família src/metabolismo
20.
BMC Complement Altern Med ; 17(1): 82, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28143473

RESUMO

BACKGROUND: Artemisia campestris L. (Asteraceae) is a medicinal herb traditionally used to treat hypertension and many other diseases. Hence, this study is aimed to analyze the essential oil of A. campestris L (AcEO) and to investigate the antiplatelet, antioxidant effects and the mechanisms of its vasorelaxant effect. METHODS: The chemical composition of AcEO was elucidated using GC/MS analysis. Then, the antioxidant effect was tested on DPPH radical scavenging and on the prevention of ß-carotene bleaching. The antiplatelet effect was performed on the presence of the platelet agonists: thrombin and ADP. The mechanism of action of the vasorelaxant effect was studied by using the cellular blockers specified to explore the involvement of NO/GC pathway and in the presence of calcium channels blockers and potassium channels blockers. RESULTS: AcEO is predominated by the volatiles: spathulenol, ß-eudesmol and p-cymene. The maximal antioxidant effect was obtained with the dose 2 mg/ml of AcEO. The dose 1 mg/ml of AcEO showed a maximum antiplatelet effect of, respectively 49.73% ±9.54 and 48.20% ±8.49 on thrombin and ADP. The vasorelaxation seems not to be mediated via NOS/GC pathway neither via the potassium channels. However, pretreatment with calcium channels blockers attenuated this effect, suggesting that the vasorelaxation is mediated via inhibition of L-type Ca2+ channels and the activation of SERCA pumps of reticulum plasma. CONCLUSION: This study confirms the antioxidant, antiplatelet and vasorelaxant effects of A.campestris L essential oil. However, the antihypertensive use of this oil should be further confirmed by the chemical fractionation and subsequent bio-guided assays.


Assuntos
Antioxidantes/isolamento & purificação , Artemisia/química , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Inibidores da Agregação de Plaquetas/isolamento & purificação , Vasodilatadores/isolamento & purificação , Animais , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Aorta/efeitos dos fármacos , Camundongos , Marrocos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/toxicidade , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/toxicidade , Ratos , Ratos Wistar , Vasodilatadores/farmacologia , Vasodilatadores/toxicidade , beta Caroteno/farmacologia
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