RESUMO
. Introducción: El dengue es la enfermedad viral transmitida por mosquitos de más rápida propagación en el mundo. A pesar de la alta incidencia de la enfermedad no existe tratamiento antiviral efectivo ni vacuna aprobada para su uso contra esta infección. La planta Ageratina havanensis ha sido ampliamente utilizada por nuestra cultura popular y en otros países debido a sus diversas propiedades biológicas. Objetivo: Evaluar la actividad antiviral de cuatro extractos provenientes de Ageratina havanensis y dos flavonoides aislados de dicha planta frente al virus dengue 2. Métodos: La pesquisa primaria de actividad antiviral de cada extracto y flavonoide se realizó mediante el ensayo de detección de la productividad vírica, y se evaluó la acción virucida de los extractos etanólico de tallo y butanólico de hoja. Resultados: Todos los extractos inhibieron la replicación viral al evidenciarse disminución del número de placas de lisis, sin embargo, no se evidenció disminución del título infectivo viral en el ensayo virucida. El tratamiento con la sakuranetina mostró valores de inhibición de la productividad viral entre 61-91 por ciento, y para la 7-metoxiaromadendrina se registraron valores de reducción viral entre 64-86 por ciento. Conclusiones: Los extractos y flavonoides aislados de Ageratina havanensis mostraron acción antiviral. Los extractos etanólico de tallo y butanólico de hojas no poseen acción virucida sobre la cepa viral empleada. El presente trabajo constituye el primer informe respecto a la evaluación de extractos y compuestos aislados de A. havanensis frente al virus dengue(AU)
Introduction: Dengue is the fastest spreading mosquito-borne viral disease worldwide. Despite its high incidence, no effective antiviral treatment or vaccine has been approved for use against this infection. The plant Ageratina havanensis has been widely used in our folk culture and in other countries due to its various biological properties. Objective: Evaluate the antiviral activity of four extracts from Ageratina havanensis and two flavonoids isolated from that plant against the dengue 2 virus. Methods: Primary screening of the antiviral activity of each extract and flavonoid was conducted by viral productivity detection assay, and an evaluation was carried out of the virucidal action of the stem ethanolic extract and the leaf butanolic extract. Results: All the extracts inhibited viral replication by a reduction in the number of lysis plates. However, no evidence was found of a reduced viral infective titer in the virucidal assay. Treatment with sakuranetin achieved viral productivity inhibition values of 61 percent-91 percent, whereas 7-methoxyaromadendrin obtained viral reduction values of 64 percent-86 percent Conclusions: The extracts and flavonoids isolated from Ageratina havanensis displayed antiviral activity. The stem ethanolic extract and the leaf butanolic extract do not have a virucidal action against the viral strain used. The paper is the first report about the effect of extracts and compounds isolated from A. havanensis against the dengue virus(AU)
Assuntos
Humanos , Microscopia Eletrônica de Transmissão e Varredura , Ageratina , Dengue , Vírus da DengueRESUMO
Ageratina havanensis (Kunth) R. M. King & H. Robinson is a species of flowering shrub in the family Asteraceae, native to the Caribbean and Texas. The aim of this work was to compare the quantitative chemical composition of extracts obtained from Ageratina havanensis in its flowering and vegetative stages with the antioxidant potential and to determine the effects on P-glycoprotein (P-gp) function. The quantitative chemical composition of the extracts was determined quantifying their major flavonoids by UPLC-ESI-MS/MS and by PCA analysis. The effects of the extracts on P-gp activity was evaluated by Rhodamine 123 assay; antioxidant properties were determined by DPPH, FRAP and inhibition of lipid peroxidation methods. The obtained results show that major flavonoids were present in higher concentrations in vegetative stage than flowering stage. In particular, the extracts obtained in the flowering season showed a significantly higher ability to sequester free radicals compared to those of the vegetative season, meanwhile, the extracts obtained during the vegetative stage showed a significant inhibitory effect against brain lipid peroxidation and a strong reductive capacity. This study also showed the inhibitory effects of all ethanolic extracts on P-gp function in 4T1 cell line; these effects were unrelated to the phenological stage. This work shows, therefore, the first evidence on: the inhibition of P-gp function, the antioxidant effects and the content of major flavonoids of Ageratina havanensis. According to the obtained results, the species Ageratina havanensis (Kunth) R. M. King & H. Robinson could be a source of new potential inhibitors of drug efflux mediated by P-gp. A special focus on all these aspects must be taking into account for future studies.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Ageratina/química , Antioxidantes/química , Antioxidantes/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Estrutura Molecular , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
The antiviral activity of extracts obtained from Ageratina havanensis (Kunth) R.M.King & H.Rob., Asteraceae, against rabbit vesivirus (RaV) (Caliciviridae) and human herpes simplex viruses type 1 and 2 (HSV-1, HSV-2) (Herpesviridae) were analyzed, and the main metabolites from the most active extract were isolated and characterized. The antiviral properties were investigated by measuring the inhibition of viral-induced cytopathic effect in Vero cells. The strongest inhibitory effects were found for ethyl acetate extract from leaves (SI=5 for RaV and SI=5.4 for HSV-1). The crude ethyl acetate extract was further fractionated by chromatographic methods and the structures of isolated compounds were established through comprehensive spectroscopic analyses, including IR, 2D NMR and MS. Four flavonoids were identified: 5,4'-dihydroxy-7-methoxyflavanone (sakuranetin), 3,5,4'-trihydroxy-7-methoxyflavanone (7-methoxyaromadendrin), 4'-O-β-D-glucosyl-5,3'-dihydroxy-7-methoxyflavanone (4'-O-β-D-glucosyl-7-methoxy-eriodictyol) and 4'-O-β-D-glucosyl-5-hydroxy-7-methoxyflavanone (4'-O-β-D-glucosylsakuranetin). This is the first report on antiviral activity for Ageratina havanensis.