RESUMO
As part of our search of bioactive saponins from Brazilian plants, phytochemical study of the seeds of Inga laurina led to the isolation of a new complex triterpenoid saponin, named ingasaponin. It is the first saponin isolated from a species of Inga genus. It was isolated by using chromatographic methods and its structural elucidation was performed using detailed analyses of (1)H and (13)C NMR spectra including 2D-NMR spectroscopic techniques and chemical conversions. Its structure was established as 21-[[(2E,6S)-6-[[6-deoxy-4-O-[(2E,6S)-6-[(ß-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(ß-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(ß-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(ß-D-glucopyranosyl)oxy]-2-(hydroxymethyl)-6-methyl-1-oxo-2,7-octadienyl]oxy]-16-hydroxy-3-[[O-ß-D-xylopyranosyl-(1 â 2)-O-α-L-arabinopyranosyl-(1 â 6)-2-(acetylamino)-2-deoxy-ß-D-glucopyranosyl]oxy]-(3ß,16α,21ß)-olean-12-en-28-oic acid O-α-L-arabinofuranosyl-(1 â 4)-O-[ß-D-glucopyranosyl-(1 â 3)]-O-6-deoxy-α-L-mannopyranosyl-(1 â 2)-ß-D-glucopyranosyl ester (1). The hemolytic potential of 1 was evaluated using in vitro assays, and its adjuvant activity on the cellular immune response against ovalbumin antigen was investigated using in vivo models.
Assuntos
Adjuvantes Imunológicos/farmacologia , Fabaceae/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Animais , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Masculino , Camundongos , Estrutura Molecular , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Saponinas/química , Saponinas/farmacologia , Sementes/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Entre as diversas atividades biológicas relatadas para as saponinas, merecem destaque aquelas relacionadas ao aumento da resposta imune e a ruptura das membranas dos eritrócitos. No desenvolvimento de vacinas, ambas as propriedades exercem atividades antagônicas, contudo, as informações sobre as relações estrutura-atividade são relativamente escassas e, às vezes, conflitantes. O presente trabalho visa contribuir no estabelecimento das relações estruturais envolvidas com as atividades imunoadjuvante e hemolítica de saponinas triterpênicas. Para isso, foram selecionadas vinte saponinas de estrutura triterpênica, isoladas das espécies Aesculus hippocastanum, Dolichos lablab e Glycine max. A relação entre grupamentos substituintes do anel triterpênico e as atividades biológicas foi estudada mediante análise de agrupamentos e análise de componentes principais. Os resultados confirmam a importância da presença de açúcares em C-3 para a atividade hemolítica. Porém o efeito causado pela presença de uma hidroxila em C-16, de CH2OH em C-17, de uma acetila em C-22 e de um grupamento acila em C-21 sobre essa atividade parece ser mais acentuado. Já a presença de uma hidroxila em C-21, de uma metila em C-17 e de dois açúcares ligados à aglicona parece ser determinante para a atividade imunoadjuvante. Além disso, observa-se a existência de uma relação inversa entre as atividades hemolítica e imunoadjuvante.
Among the various biological activities reported for saponins, those related with increase immune response and the destruction of the membrane of red blood cells deserve attention. In the development of vaccines, these properties exert antagonistic activities. However, the information about the structure-activity relationships is relatively scarce and sometimes contradictory. This paper aims to contribute to the establishment of structural relations involved with the hemolytic and adjuvant activities of triterpenic saponins by the analysis of the different groups linked to aglycone, with the use of multivariate statistical techniques. For this, we had twenty triterpenic saponins previously isolated from Aesculus hippocastanum, Dolichos lablab. and Glycine max species. Their adjuvant and hemolytic activities are available in the literature. These saponins were analyzed as groups linked to the triterpenic ring and biological activities resulting in an array of date that was submitted to cluster analysis and principal components analysis. The results confirm the importance of sugars in C-3 for hemolytic activity. However, the effect caused by the presence of a hydroxyl in C-16, CH2OH in C-17, acetyl in C-22 and acyl in C-21 on the hemolytic activity seems to be more important. On the other way, the presence of a hydroxyl in C-21, a methyl in C-17 and two sugars linked to aglycone seem determinant for adjuvant activity. Moreover, there is an inverse relationship between adjuvant and hemolytic activities in the set of saponins analyzed.