RESUMO
In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA and phenylephrine (Phe)-induced contractions (pD2 = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe pathways or α1 adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative contractionresponse curves, indicating a noncompetitive antagonism of α1 adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD2 = 5.50 ± 0.22 and 4.37 ± 0.12). The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA+. Furthermore, in the presence of apamin, glibenclamide, BaCl2 or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K+ channels (SKCa), ATP-sensitive K+ channels (KATP), inward rectifier K+ channels (Kir) and voltage-dependent K+ channels (KV), respectively. FGAL inhibited and rightward shifted CaCl2-induced cumulative contraction-response curves in both depolarizing medium (high K+) and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca2+ influx through voltage-gated calcium channels (CaV) and receptor operated channels (ROCs), respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca2+-free medium, indicating inhibition of Ca2+ release from the sarcoplasmic reticulum (SR). FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V). Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α1 adrenergic receptors, the non-selective opening of K+ channels, inhibition of Ca2+ influx through CaV or ROCs and the inhibition of intracellular Ca2+ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition.
Assuntos
Aorta/fisiologia , Fabaceae/química , Flavonoides/farmacologia , Vasodilatação/efeitos dos fármacos , Aminofilina/farmacologia , Animais , Aorta/efeitos dos fármacos , Cloreto de Cálcio/farmacologia , Flavonoides/química , Técnicas In Vitro , Masculino , Milrinona/farmacologia , Contração Miocárdica/efeitos dos fármacos , Fenilefrina/farmacologia , Piperazinas/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Purinas/farmacologia , Ratos Wistar , Citrato de Sildenafila , Sulfonamidas/farmacologia , Verapamil/farmacologiaRESUMO
Mimosa paraibana Barneby foi submetida a um estudo fitoquímico para o isolamento de seus constituintes químicos, através de métodos cromatográficos usuais, e posterior identificação estrutural, utilizando-se métodos espectroscópicos de RMN ¹H e 13C uni e bidimensionais, além de comparações com modelos da literatura. Deste estudo pioneiro, foram isolados e identificados cinco constituintes da fase clorofórmica: uma mistura dos esteróides, β-sitosterol e estigmasterol, a 15¹-hidroxi-feofitina A, a 5,7-dihidroxiflavanona, o 3,4,5-trihidroxibenzoato de etila e o ácido p-cumárico. A atividade antioxidante das fases hexânica, clorofórmica e acetato de etila foi avaliada utilizando o radical estável DPPH (1,1-difenil-2-picril-hidrazil) e os resultados comparados com o padrão ácido ascórbico. A avaliação da citotoxicidade das fases foi realizada empregando-se o ensaio de letalidade contra Artemia salina. Dos extratos avaliados, somente o hexânico mostrou baixa toxicidade.
The phytochemical study of Mimosa paraibana Barneby led to the isolation of its chemical constituents, through the usual chromatographic methods, and further structural identification, using ¹H and 13C NMR spectroscopic methods based on one and two-dimensional techniques, in addition to comparison with literature data. From this pioneering investigation with M. paraibana, five constituents were isolated and identified from the chloroform extract: a mixture of β-sitosterol and stigmasterol, 15¹-hydroxy-phaeophytin A, 5,7-dihydroxyflavanone, ethyl 3,4,5-trihydroxybenzoate and p-coumaric acid. The antioxidant activity of the hexane, chloroform and ethyl acetate extracts of M. paraibana were measured using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay and the results compared with standard ascorbic acid. The toxicity activity of the extracts were performed using the bioassay of Artemia salina.