In vitro and in vivo anti-malarial activity of limonoids isolated from the residual seed biomass from Carapa guianensis (andiroba) oil production.

Autor: Pereira TB, Rocha E Silva LF, Amorim RC, Melo MR, Zacardi de Souza RC, Eberlin MN, Lima ES, Vasconcellos MC, Pohlit AM; Laboratório de Princípios Ativos da Amazônia, Coordenação de Tecnologia e Inovação, Instituto Nacional de Pesquisas da Amazônia, Avenida André Araújo, 2936, Petrópolis, 69067-375 Manaus, Amazonas, Brasil. ampohlit@inpa.gov.br.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2014 Aug 13; Vol. 13, pp. 317. Date of Electronic Publication: 2014 Aug 13.
DOI: 10.1186/1475-2875-13-317
Abstrakt: 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: 6α-acetoxyepoxyazadiradione (1), andirobin (2), 6α-acetoxygedunin (3) and 7-deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and chromatography techniques) and 6α-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: 6α-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties.
Databáze: MEDLINE
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