title: Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents.
abstract: BACKGROUND
  Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models.
  
  
  METHODS
  The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed.
  
  
  RESULTS
  Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of HERP. Also, formononetin inhibited (P<0.001) the nociception induced by glutamate similarly to 30mg/kg of HERP. There were no significant differences in the open field test after HERP administration, but formononetin decrease the spontaneous motor behaviour. Regarding the anti-inflammatory assessment, the HERP (10 and 30mg/kg, P<0.05) and formononetin (P<0.001) treatments caused a significant inhibition of the oedema response. All doses of HERP (3, 10, and 30mg/kg, P<0.05) and formononetin (P<0.001) also inhibited the carrageenan-induced leukocyte migration. In both cases, the results for the HERP at 30mg/kg and formononetin were similar.
  
  
  CONCLUSIONS
  The HERP and formononetin presented significant anti-inflammatory activity. Moreover, the HERP presented antinociceptive action on inflammatory and neurogenic pain without motor side effects, possibly due to the action of other constituents present in the extract. These results, together, support the popular usage of this natural product.
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lima Cavendish
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, Av. Marechal Rondon, Cidade Universitária, CEP 49100-000 São Cristóvão, Sergipe, Brazil.
authors.forename: Jandson
authors.initials: J
authors.lastname: de Souza Santos
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Belo Neto
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Ailma
authors.initials: A
authors.lastname: Oliveira Paixão
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Juciele
authors.initials: J
authors.lastname: Valéria Oliveira
authors.affiliation: Departamento de Biologia, Universidade Federal de Sergipe, Av. Marechal Rondon, Cidade Universitária, CEP 49100-000 São Cristóvão, Sergipe, Brazil.
authors.forename: Edilson
authors.initials: E
authors.lastname: Divino de Araujo
authors.affiliation: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. do Café, CEP 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Andresa Aparecida
authors.initials: AA
authors.lastname: Berretta E Silva
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, Av. Marechal Rondon, Cidade Universitária, CEP 49100-000 São Cristóvão, Sergipe, Brazil. Electronic address: sthomazzi@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Maria Thomazzi
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Cordeiro Cardoso
authors.affiliation: Instituto de Tecnologia e Pesquisa (ITP), Universidade Tiradentes, Av. Murilo Dantas, 300, Farolândia, CEP 49032-490 Aracaju, Sergipe, Brazil.
authors.forename: Margarete
authors.initials: M
authors.lastname: Zanardo Gomes
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005557:Formaldehyde; D018698:Glutamic Acid; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D011429:Propolis / Q000737:chemistry*; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007529:Isoflavones; D005557:Formaldehyde; C007768:formononetin; D018698:Glutamic Acid; D002351:Carrageenan; D011429:Propolis; D019342:Acetic Acid
keywords: Analgesics; Flavonoids; Formononetin; Inflammation.; Propolis