title: In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa.
abstract: BACKGROUND
  To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity.
  
  
  METHODS
  Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted.
  
  
  RESULTS
  At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153.
  
  
  CONCLUSIONS
  The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.
authors.affiliation: Departamento de Genética, Evolução e Bioagentes, Instituto de Biologia, Universidade de Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Ana Carolina A V
authors.initials: AC
authors.lastname: Kayano
authors.forename: Stefanie C P
authors.initials: SC
authors.lastname: Lopes
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: Bueno
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Cabral
authors.forename: Wanessa C
authors.initials: WC
authors.lastname: Souza-Neiras
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Yamauchi
authors.forename: Mary A
authors.initials: MA
authors.lastname: Foglio
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: João Carlos P
authors.initials: JC
authors.lastname: Mello
authors.forename: Fabio T M
authors.initials: FT
authors.lastname: Costa
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D001938:Brazil; D029911:Caesalpinia / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal / Q000737:chemistry; D016788:Plasmodium chabaudi / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D012376:Rodent Diseases / Q000188:drug therapy / Q000469:parasitology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D010936:Plant Extracts; D000077332:Artesunate; D011794:Quercetin