title: Anti-malarial activity and toxicity assessment of Himatanthus articulatus, a plant used to treat malaria in the Brazilian Amazon.
abstract: BACKGROUND
  Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus.
  
  
  METHODS
  Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity--TEAC; lipid peroxidation--TBARS, and nitrites and nitrates--NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice.
  
  
  RESULTS
  Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies.
  
  
  CONCLUSIONS
  The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Rua Augusto Corrêa 1, 68075-110, Belém, PA, Brazil. valdicleyvale@yahoo.com.br.
authors.forename: Valdicley V
authors.initials: VV
authors.lastname: Vale
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Rua Augusto Corrêa 1, 68075-110, Belém, PA, Brazil. tc-vilhena@hotmail.com.
authors.forename: Thyago C
authors.initials: TC
authors.lastname: Vilhena
authors.affiliation: Departamento de Botânica, Museu Paraense Emilio Goeldi, Belém, PA, Brazil. rafa.bio@hotmail.com.
authors.forename: Rafaela C Santos
authors.initials: RC
authors.lastname: Trindade
authors.affiliation: Departamento de Botânica, Museu Paraense Emilio Goeldi, Belém, PA, Brazil. mcoelho@museu-goeldi.br.
authors.forename: Márlia Regina C
authors.initials: MR
authors.lastname: Ferreira
authors.affiliation: Laboratório de Pesquisa em Estresse Oxidativo, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, PA, Brazil. percario@ufpa.br.|US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA. percario@ufpa.br.
authors.forename: Sandro
authors.initials: S
authors.lastname: Percário
authors.affiliation: Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. lfsoares.luciana@gmail.com.
authors.forename: Luciana F
authors.initials: LF
authors.lastname: Soares
authors.affiliation: Departamento de Patologia Veterinária e Medicina Preventiva, Instituto de Saúde e Produção Animal (ISPA), Universidade Federal Rural da Amazônia, Belém, PA, Brazil. wkarton@terra.com.br.
authors.forename: Washington Luiz A
authors.initials: WL
authors.lastname: Pereira
authors.affiliation: Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil. celiobrandao@ef.ufop.br.
authors.forename: Geraldo C
authors.initials: GC
authors.lastname: Brandão
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Rua Augusto Corrêa 1, 68075-110, Belém, PA, Brazil. alaidebraga@terra.com.br.|Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. alaidebraga@terra.com.br.
authors.forename: Alaíde B
authors.initials: AB
authors.lastname: Oliveira
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Rua Augusto Corrêa 1, 68075-110, Belém, PA, Brazil. fanidolabela@gmail.com.|Programa de Pós-graduação em Inovação Farmacêutica, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Belém, PA, Brazil. fanidolabela@gmail.com.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Dolabela
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde (ICS), Universidade Federal do Pará (UFPA), Rua Augusto Corrêa 1, 68075-110, Belém, PA, Brazil. flavio@ufpa.br.
authors.forename: Flávio
authors.initials: F
authors.lastname: De Vasconcelos
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity*; D029062:Apocynaceae / Q000737:chemistry*; D001938:Brazil; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity*; D018547:Plant Stems / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D010936:Plant Extracts