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|Title:||In vitro and in vivo anti-malarial activity of limonoids isolated from the residual seed biomass from Carapa guianensis (andiroba) oil production|
|Authors:||Pereira, Tiago B.|
Silva, Luiz Francisco Rocha e
Amorim, Rodrigo C.N.
Melo, Márcia R.S.
Zacardi de Souza, Rita C.
Eberlin, M. N.
Lima, Emerson Silva
Vasconcellos, Marne Carvalho de
Pohlit, Adrian Martin
7 Deacetoxy 7 Oxogedunin
In Vitro Study
In Vivo Study
Minimum Inhibitory Concentration
Plasmodium Berghei Infection
Bagg Albino Mouse
Inhibitory Concentration 50
Mice, Inbred Balb C
|metadata.dc.relation.ispartof:||Volume 13, Número 1|
|Abstract:||Background: Carapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and particularly symptoms related to malaria. Abundant residual pressed seed material (RPSM) results as a by-product of carapa or andiroba oil production. The objective of this study was to evaluate the in vitro and in vivo anti-malarial activity and cytotoxicity of limonoids isolated from C. guaianensis RPSM.Methods. 6-acetoxyepoxyazadiradione (1), andirobin (2), 6-acetoxygedunin (3) and 7-deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and chromatography techniques) and 6-hydroxy-deacetylgedunin (5) (prepared from 3) were evaluated using the micro test on the multi-drug-resistant Plasmodium falciparum K1 strain. The efficacy of limonoids 3 and 4 was then evaluated orally and subcutaneously in BALB/c mice infected with chloroquine-sensitive Plasmodium berghei NK65 strain in the 4-day suppressive test.Results: In vitro, limonoids 1-5 exhibited median inhibition concentrations (IC50) of 20.7-5.0 μM, respectively. In general, these limonoids were not toxic to normal cells (MRC-5 human fibroblasts). In vivo, 3 was more active than 4. At oral doses of 50 and 100 mg/kg/day, 3 suppressed parasitaemia versus untreated controls by 40 and 66%, respectively, evidencing a clear dose-response.Conclusion: 6-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties. © 2014 Pereira et al.; licensee BioMed Central Ltd.x.|
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