title: In vitro and in vivo anti-malarial activity of limonoids isolated from the residual seed biomass from Carapa guianensis (andiroba) oil production.
abstract: 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.
  
  
  CONCLUSIONS
  6α-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties.
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Pereira
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Rocha E Silva
authors.forename: Rodrigo C N
authors.initials: RC
authors.lastname: Amorim
authors.forename: Márcia R S
authors.initials: MR
authors.lastname: Melo
authors.forename: Rita C
authors.initials: RC
authors.lastname: Zacardi de Souza
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Lima
authors.forename: Marne C
authors.initials: MC
authors.lastname: Vasconcellos
authors.affiliation: 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.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Pohlit
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D036701:Limonins / Q000494:pharmacology* / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D012639:Seeds / Q000737:chemistry
chemical_list: D000962:Antimalarials; D036701:Limonins; D010936:Plant Extracts