In vitro and in vivo anti-malarial activity of plants from the Brazilian Amazon

Malaria Journal

Research

Antoniana U. Krettli¹  Julia P. Coutinho¹  Francisco C. M. Chaves²  Marcia R. S. Melo³  Marne C. Vasconcellos⁴  Jakeline M. P. Santos⁴  Ana Paula A. Boleti⁴  Emerson S. Lima⁴  Wanderli P. Tadei⁵  Jaqueline S. Costa⁶  Rodrigo C. N. Amorim⁶  Adrian M. Pohlit⁶  Neila S. Picanço⁷  Renata B. S. Lima⁸  Luiz F. Rocha e Silva⁸ 

[1] Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Avenida Augusto de Lima, 1715, Barro Preto, 30190-002, Belo Horizonte, Minas Gerais, Brazil;Embrapa Amazônia Ocidental, Rodovia AM-010, Km 29 (Estrada Manaus/Itacoatiara), Caixa Postal 319, 69010-970, Manaus, Amazonas, Brazil;Escola Superior de Ciências da Saúde, Universidade Estadual do Amazonas, Avenida Carvalho Leal, 1777, Cachoeirinha, 69065-001, Manaus, Amazonas, Brazil;Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Rua Comendador Alexandre Amorim, 330, Aparecida, 69103-000, Manaus, Amazonas, Brazil;Laboratório de Malária e Dengue, Coordenação de Sociedade, Ambiente e Saúde, Instituto Nacional de Pesquisas da Amazônia, Avenida André Araújo, 2936, Petrópolis, 69067-375, Manaus, Amazonas, Brazil;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, Brazil;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, Brazil;Programa de Pós-graduação em Biotecnologia, Universidade Federal do Amazonas, Avenida Gal. Rodrigo Otávio Jordão Ramos, 3000, Coroado I, Campus Universitário, Bloco M, Setor Sul, 69077-000, Manaus, Amazonas, Brazil;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, Brazil;Programa de Pós-graduação em Biotecnologia, Universidade Federal do Amazonas, Avenida Gal. Rodrigo Otávio Jordão Ramos, 3000, Coroado I, Campus Universitário, Bloco M, Setor Sul, 69077-000, Manaus, Amazonas, Brazil;Centro Universitário do Norte, Rua Dez de Julho, 873, Centro, 69010-060, Manaus, Amazonas, Brazil;

关键词: Plasmodium falciparum;    Plasmodium berghei;    Antiplasmodial;    Cytotoxic;    Anacardium occidentale;    Andropogon leucostachyus;    Croton cajucara;    Paullinia cupana;    Xylopia amazonica;    Zanthoxylum djalma;   

DOI  :  10.1186/s12936-015-0999-2

 received in 2015-05-19, accepted in 2015-11-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated.MethodsSixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice.ResultsHigh in vitro antiplasmodial activity (IC50 = 6.4–9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71 % suppression of P. berghei parasitaemia versus untreated controls).ConclusionsEthnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present.

【 授权许可】

CC BY   
© Lima et al. 2015