title: Chemical composition and antinociceptive effect of aqueous extract from Rourea induta Planch. leaves in acute and chronic pain models.
abstract: BACKGROUND
  Rourea induta Planch. is a small tree or shrub growing wild in Brazil and belonging to the Connaraceae family. It is used for the treatment of Chagas disease and as antirheumatic in folk medicine. This study was designed to investigate the antinociceptive activity of the aqueous extract (AERi) of Rourea induta leaves in rodents, as well as isolate and identify components that can be responsible for its effect.
  
  
  METHODS
  The antinociceptive effect of orally administered AERi was evaluated in behavioral models of acute (formalin) and chronic [complete Freund׳s adjuvant (CFA)] pain in mice. We also investigated the possible involvement of opioid receptors and proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the antinociceptive effect of the AERi. In addition, a nonspecific effect of AERi was evaluated by measuring locomotor activity and corporal temperature. Finally, we performed a phytochemical analysis of AERi.
  
  
  RESULTS
  HPLC titration revealed the presence of hyperin (21.6 mg/g), quercetin-3-O-β-xyloside (4.4 mg/g), quercetin-3-O-α-arabinofuranoside (12.0 mg/g), and quercetin (2.1 mg/g). It was also possible to isolate minor constituents׳ chlorogenic acid, neochlorogenic acid and procyanidin C1. The oral administration of AERi (100 mg/kg) significantly inhibited the neurogenic (37 ± 5%) and inflammatory (34 ± 7%) phases of formalin-induced pain. Acute and repeated treatment of animals with AERi (100 mg/kg, p.o.) once a day markedly reduced the mechanical hypersensitivity response induced by CFA, and this effect was evident until the day 10. Moreover, repeated treatment with AERi (100 mg/kg, p.o.) significantly reduced the levels of IL-1β and TNF-α in the paw (22 ± 7% and 50 ± 19%) and in the spinal cord (100% and 100%) when compared to the CFA group. The AERi (100 mg/kg, p.o.) markedly reduced biting behavior induced by intrathecal injection of TNF-α (81 ± 11%). Finally, the effect of AERi was not associated with changes in locomotor activity or the corporal temperature of animals.
  
  
  CONCLUSIONS
  These data show that aqueous extract of Rourea induta has significant antinociceptive action, which seems to be associated with an inhibition of pro-inflammatory cytokines activated pathways. These findings support the ethnomedical uses of this plant.
authors.affiliation: Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Av. Prefeito Lothário Meissner, 632 Jardim Botânico, 80210-170 Curitiba, PR, Brazil; Institut de Chimie de Substances Naturelles, CNRS, 1 Avenue de La Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Milena
authors.initials: M
authors.lastname: Kalegari
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Murilo Luiz
authors.initials: ML
authors.lastname: Cerutti
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil; Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Sérgio José
authors.initials: SJ
authors.lastname: Macedo-Júnior
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Franciane
authors.initials: F
authors.lastname: Bobinski
authors.affiliation: Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Av. Prefeito Lothário Meissner, 632 Jardim Botânico, 80210-170 Curitiba, PR, Brazil.
authors.forename: Marilis Dallarmi
authors.initials: MD
authors.lastname: Miguel
authors.affiliation: Institut de Chimie de Substances Naturelles, CNRS, 1 Avenue de La Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Eparvier
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: adair.santos@ufsc.br.
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Institut de Chimie de Substances Naturelles, CNRS, 1 Avenue de La Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Stien
authors.affiliation: Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Av. Prefeito Lothário Meissner, 632 Jardim Botânico, 80210-170 Curitiba, PR, Brazil.
authors.forename: Obdulio Gomes
authors.initials: OG
authors.lastname: Miguel
mesh_terms: D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D031961:Connaraceae / Q000737:chemistry; D005260:Female; D005557:Formaldehyde; D005620:Freund's Adjuvant; D053583:Interleukin-1beta; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D059808:Polyphenols / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000700:Analgesics; D053583:Interleukin-1beta; D010936:Plant Extracts; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D005620:Freund's Adjuvant
keywords: Anti-inflammatory; Antinociception; Connaraceae; Cytokines; Polyphenols; Rourea induta