Estudios para la evaluación de la actividad antiinflamatoria de compuestos bioactivos obtenidos a partir de las hojas de la planta Agave brittoniana Trel
Fecha
2018
Autores
Vázquez Martín, Arlena
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Editor
Universidad Central “Marta Abreu” de Las Villas. Facultad de Química Farmacia. Departamento de Licenciatura en Química
Resumen
Los metabolitos secundarios mayoritarios del Agave brittoniana Trel. son las saponinas y sapogeninas esteroidales. Si bien el crudo de saponinas ha mostrado actividad antiinflamatoria en modelos experimentales crónicos, no se conoce de ningún estudio referente a las sapogeninas o su mecanismo de acción frente a blancos terapéuticos. Para comprobar el efecto antiinflamatorio de las sapogeninas esteroidales se realizaron estudios in silico e in vivo. Se desarrolló un modelo QSAR para predecir la inhibición de las sapogeninas frente a la enzima ADAM-17 a través de un cribado virtual. La obtención de las sapogeninas se realizó combinado la hidrólisis ácida y la cromatografía de columna sílica-gel fase normal. La actividad antiinflamatoria in vivo fue evaluada empleando modelo crónico de granuloma inducido por pellet de algodón empleando cinco grupos experimentales. El modelo QSAR mostró buena capacidad predictiva (Qext= 52.22 %) y predijo de manera eficaz el potencial de inhibición en todas las sapogeninas frente al ADAM-17 siendo la yucagenina, la clorogenina y la rockogenina las de mejores resultados. Se logró de forma efectiva el fraccionamiento del crudo de sapogeninas, la fracción rica en yucagenina con mayor grado de pureza se empleó en estudio experimental. El estudio in vivo corroboró que las fracciones de sapogeninas evaluadas mostraron buenas propiedades antiinflamatorias, aunque menores que la indometacina. El crudo de sapogeninas mostró el mejor resultado, conociendo que la yucagenina es la sapogenina mayoritaria podemos concluir que esta molécula presenta la mayor contribución al efecto antiinflamatorio.
Palabras claves:
Agave brittoniana Trel., sapogeninas esteroidales, antiinflamatorio, QSAR, ADAM-17, cromatografía, granuloma
The major secondary metabolites of Agave brittonian Trel. are steroidal saponins and sapogenins. Although saponin crude oil has shown anti-inflammatory activity in chronic experimental models, there is no known study of sapogenins or their mechanism of action against therapeutic targets. To check the anti-inflammatory effect of the steroidal sapogenins, in silico and in vivo studies were carried out. A QSAR model was developed to predict the inhibition of sapogenins against the ADAM-17 enzyme through a virtual screening. The sapogenins were obtained by combining the acid hydrolysis and the silica-gel normal phase column chromatography. Anti-inflammatory activity in vivo was evaluated by using a chronic model of granuloma induced by cotton pellets using five experimental groups. The QSAR model showed good predictive capacity (Qext = 52.22%) and effectively predicted the potential for inhibition in all sapogenins against ADAM-17, with yucagenin, chlorogenin and rockogenin providing the best results. The fractionation of sapogenin crude was effectively achieved, the fraction rich in yucagenin with a higher degree of purity was used in an experimental study. The in vivo study corroborated that the sapogenin fractions evaluated showed good anti-inflammatory properties, although less than indomethacin. Sapogenin crude showed the best result, knowing that yucagenin is the major sapogenin we can conclude that this molecule has the greatest contribution to the anti-inflammatory effect. Key words: Agave brittonian Trel, steroidal sapogenins, anti-inflammatory, QSAR, ADAM-17, chromatography, granuloma
The major secondary metabolites of Agave brittonian Trel. are steroidal saponins and sapogenins. Although saponin crude oil has shown anti-inflammatory activity in chronic experimental models, there is no known study of sapogenins or their mechanism of action against therapeutic targets. To check the anti-inflammatory effect of the steroidal sapogenins, in silico and in vivo studies were carried out. A QSAR model was developed to predict the inhibition of sapogenins against the ADAM-17 enzyme through a virtual screening. The sapogenins were obtained by combining the acid hydrolysis and the silica-gel normal phase column chromatography. Anti-inflammatory activity in vivo was evaluated by using a chronic model of granuloma induced by cotton pellets using five experimental groups. The QSAR model showed good predictive capacity (Qext = 52.22%) and effectively predicted the potential for inhibition in all sapogenins against ADAM-17, with yucagenin, chlorogenin and rockogenin providing the best results. The fractionation of sapogenin crude was effectively achieved, the fraction rich in yucagenin with a higher degree of purity was used in an experimental study. The in vivo study corroborated that the sapogenin fractions evaluated showed good anti-inflammatory properties, although less than indomethacin. Sapogenin crude showed the best result, knowing that yucagenin is the major sapogenin we can conclude that this molecule has the greatest contribution to the anti-inflammatory effect. Key words: Agave brittonian Trel, steroidal sapogenins, anti-inflammatory, QSAR, ADAM-17, chromatography, granuloma
Descripción
Palabras clave
Agave Brittoniana Trel, Plantas Medicinales, Actividad Antiinflamatoria, Sapogeninas Esteroidales