RESUMEN
The aim of current study was to determinate ex vivo and chromatographic fingerprint by HPLC of four extracts of Euphorbia furcillata K. Ethyl acetate extract of Euphorbia furcillata (EaEEf) was the most effective and potent extract (Emax=98.69±1.24%) and its effect was partially endothelium-dependent. Functional vasorelaxant mechanism of action of EaEEf was determinate, EaEEf showed efficient relaxation of KCl [80 mM]-induced contraction and norepinephrine and CaCl2 contraction curves showed diminution of maximal contraction in the presence of EAEEf and EaEEf-relaxation curve was shifted to the right in the presence of L-NAME (nitric oxide synthase inhibitor) and ODQ (guanylate cyclase inhibitor). Chromatographic fingerprints analysis suggests presence of diterpenoid such as abietane, tigliane, and ingenane skeletons. Our experiments suggest the EaEEf vasorelaxant activity could be attributed to diterpenoid molecules whose mechanism involves nitric oxide production and calcium channel blockade.
Se determinoÌ el efecto vasorrelajante ex vivo y los perfiles cromatograÌficos mediante HPLC de cuatro extractos de Euphorbia furcillata K.. El extracto de acetato de etilo de E. furcillata (EaEEf) fue el maÌs eficaz y potente en la contraccioÌn inducida por norepinefrina (Emax=98.69±1.24%) y el efecto fue parcialmente dependiente del endotelio vascular. Se determinoÌ el mecanismo de accioÌn vasorrelajante para EaEEf, este mostroÌ ser eficaz sobre la contraccioÌn inducida por KCl [80 mM] y la curva de contraccioÌn en respuesta a norepinefrina y CaCl2 en presencia de EaEEf mostroÌ disminucioÌn en la contraccioÌn maÌxima, mientras que la curva de relajacioÌn de EaEEf en presencia de L-NAME (inhibidor de oÌxido niÌtrico sintasa) y ODQ (inhibidor de guanilato ciclasa) se desplazoÌ hacia la derecha. El anaÌlisis cromatograÌfico de EaEEf sugiere la presencia de moleÌculas diterpenoides como abietano, tigliano y esqueletos de ingenano. Nuestros resultados sugieren que el efecto vasorrelajante de EaEEf podriÌa atribuirse a moleÌculas diterpenoides, cuyo mecanismo de accioÌn involucra la produccioÌn de oÌxido niÌtrico y bloqueo de canales de calcio.
Asunto(s)
Animales , Masculino , Ratas , Vasodilatadores/farmacología , Extractos Vegetales/farmacología , Euphorbia/química , Bloqueadores de los Canales de Calcio/metabolismo , Cromatografía Líquida de Alta Presión , Ratas Wistar , GMP Cíclico/metabolismo , Óxido Nítrico/metabolismoRESUMEN
A small series of thiazolidine-2,4-dione and barbituric acid derivatives 1-4 was prepared using a short synthetic route, and all compounds were characterized by elemental analysis, mass spectrometry, and NMR ((1)H, (13)C) spectroscopy. Their in vitro relative expression of peroxisome proliferator-activated receptor α and peroxisome proliferator-activated receptor γ was evaluated. Compound 1 showed an increase in the mRNA expression of both peroxisome proliferator-activated receptor isoforms, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/kg single dose using a non-insulin-dependent diabetes mellitus rat model. The results indicated a significant decrease in plasma glucose levels. Additionally, we performed a molecular docking of compound 1 into the ligand binding pocket of peroxisome proliferator-activated receptor α and peroxisome proliferator-activated receptor γ. In these binding models, compound 1 may bind into the active site of both isoforms showing important short contacts with the peroxisome proliferator-activated receptor γ residues: Tyr 473, His 449, Ser 289, His 323; and peroxisome proliferator-activated receptor α residues: Tyr 464, His 440, Ser 280 and Tyr 314.