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

Malaria Journal

Research

Márcia RS Melo¹  Emerson S Lima²  Marne C Vasconcellos²  Rita C Zacardi de Souza³  Marcos N Eberlin³  Adrian M Pohlit⁴  Rodrigo CN Amorim⁴  Luiz F Rocha e Silva⁵  Tiago B Pereira⁶ 

[1] Escola Superior de Ciências da Saúde, Universidade Estadual do Amazonas, Avenida Carvalho Leal, 1777, Cachoeirinha, 69065-001, Manaus, Amazonas, Brasil;Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Rua Comendador Alexandre Amorim, 330, Aparecida, 69103-00, Manaus, Amazonas, Brasil;Instituto de Química, Universidade Estadual de Campinas, Caixa Postal 6154, 13083-970, Campinas, São Paulo, Brasil;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;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;Programa de Pós-graduação em Biotecnologia, Universidade Federal do Amazonas, Avenida General Rodrigo Octávio, 3000, Coroado I, Campus Universitário, 69077-000, Manaus, Amazonas, Brasil;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;Programa de Pós-graduação em Química, Universidade Federal do Amazonas, Avenida General Rodrigo Octávio, 6200, Coroado I, Campus Universitário, 69077-000, Manaus, Amazonas, Brasil;

关键词: Malaria;    6α-acetoxyepoxyazadiradione;    6α-acetoxygedunin;    Andirobin;    7-deacetoxy-7-oxogedunin;    6α-hydroxy-deacetylgedunin;    Plasmodium falciparum;    Plasmodium berghei;    Human fibroblasts;    Antiplasmodial;   

DOI  :  10.1186/1475-2875-13-317

 received in 2014-03-30, accepted in 2014-07-19,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundCarapa 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.Methods6α-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.ResultsIn 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.Conclusion6α-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties.

【 授权许可】

Unknown   
© Pereira et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.