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

• Autor(a) principal: Pereira, Tiago B.
• Data de Publicação: 2014
• Outros Autores: 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
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional do INPA
• Texto Completo: https://repositorio.inpa.gov.br/handle/1/15981
• topic: 6alpha Acetoxyepoxyazadiradione; 6alpha Acetoxygedunin; 6alpha Hydroxydeacetylgedunin; 7 Deacetoxy 7 Oxogedunin; Andirobin; Antimalarial Agent; Limonoid; Plant Extract; Unclassified Drug; Antimalarial Agent; Limonoid; Plant Extract; Animals Experiment; Animals Model; Antimalarial Activity; Carapa Guianensis; Controlled Study; Dose Response; Drug Cytotoxicity; Drug Efficacy; Drug Screening; Fibroblast; Human; Human Cell; Ic 50; In Vitro Study; In Vivo Study; Medicinal Plant; Meliaceae; Minimum Inhibitory Concentration; Mouse; Nonhuman; Seed Plant; Plasmodium Berghei Infection; Plasmodium Falciparum; Animals; Bagg Albino Mouse; Cell Line; Chemistry; Drug Effects; Female; Malaria; Meliaceae; Plasmodium Berghei; Animal; Antimalarials; Cell Line; Female; Humans; Inhibitory Concentration 50; Limonins; Malaria; Meliaceae; Mice; Mice, Inbred Balb C; Plant Extracts; Plasmodium Berghei; Plasmodium Falciparum; Seeds

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.