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

• Autor(a) principal: Lima, Renata Braga Souza
• Data de Publicação: 2015
• Outros Autores: Rocha Silva, Luiz F., Melo, Márcia R.S., Costa, Jacqueline S., Picanço, Neila Soares, Lima, Emerson Silva, Vasconcellos, Marne Carvalho de, Boleti, Ana Paula de Araújo, Santos, Jakeline M.P., Amorim, Rodrigo C.N., Chaves, Francisco Célio Maia, Coutinho, Julia Penna, Tadei, Wanderli Pedro, Krettli, Antoniana Ursine, Pohlit, Adrian Martin
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional do INPA
• Texto Completo: https://repositorio.inpa.gov.br/handle/1/15871
• topic: Alcohol; Anacardic Acid; Andropogon Leucostachyus Extract; Chloroform; Chloroquine; Clidemia Bullosa Extract; Croton Cajucara Extract; Derris Floribunda Extract; Guarana Extract; Methanol; Miconia Nervosa Extract; Monoclonal Antibody; Parkia Nitida Extract; Plant Extract; Stigmaphyllon Sinuatum Extract; Unclassified Drug; Xylopia Amazonica Extract; Zanthoxylum Djalma Batistae Extract; Antimalarial Agent; Plant Extract; Adult; Andropogon; Andropogon Leucostachyus; Animals Cell; Animals Experiment; Animals Model; Antimalarial Activity; Antimalarial Drug Resistance; Brazilian; Cell Viability; Clidemia Bullosa; Controlled Study; Croton; Croton Cajucara; Derris; Derris Floribunda; Drug Cytotoxicity; Drug Screening; Drug Selectivity; Drug Synthesis; Enzyme-linked Immunosorbent Assay; Fabaceae; Fibroblast Culture; Human; Human Cell; Ic 50; In Vitro Study; In Vivo Study; Macrophage; Malpighiaceae; Medicinal Plant; Melanoma Cell Line; Melastomataceae; Miconia Nervosa; Mouse; Nonhuman; Parasitemia; Parkia Nitida; Plant Leaf; Plasmodium Berghei Infection; Plasmodium Falciparum; Plasmodium Falciparum K1; Plasmodium Falciparum W2; Stigmaphyllon Sinuatum; Varietas; Xylopia; Xylopia Amazonica; Zanthoxylum; Zanthoxylum Djalma Batistae; Animals; Bagg Albino Mouse; Brasil; Cell Culture; Cell Survival; Chemistry; Disease Model; Drug Effects; Drug Sensitivity; Isolation And Purification; Malaria; Plant; Plasmodium Berghei; Treatment Outcome; Animal; Antimalarials; Brasil; Cell Survival; Cells, Cultured; Disease Models, Animals; Humans; Inhibitory Concentration 50; Malaria; Mice, Inbred Balb C; Parasitemia; Parasitic Sensitivity Tests; Plant Extracts; Plants; Plasmodium Berghei; Plasmodium Falciparum; Treatment Outcome

Background: The 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. Methods: Sixty-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. Results: High 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). Conclusions: Ethnobotanical 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. © 2015 Lima et al.