title: Vestitol Isolated from Brazilian Red Propolis Inhibits Neutrophils Migration in the Inflammatory Process: Elucidation of the Mechanism of Action.
abstract: Vestitol is an isoflavonoid isolated from Brazilian red propolis with potential anti-inflammatory activity. This study investigated the mechanism of action of vestitol on the modulation of neutrophil migration in the inflammatory process. Pre-treatment with vestitol at 1, 3, or 10 mg/kg reduced LPS- or mBSA-induced neutrophil migration and the release of CXCL1/KC and CXCL2/MIP-2 in vivo. Likewise, pre-treatment with vestitol at 1, 3, or 10 μM reduced the levels of CXCL1/KC and CXCL2/MIP-2 in macrophage supernatants in vitro. Moreover, the administration of vestitol (10 mg/kg) reduced leukocyte rolling and adherence in the mesenteric microcirculation of mice. The pre-treatment with vestitol (10 mg/kg) in iNOS(-/-) mice did not block its activity concerning neutrophil migration. With regard to the activity of vestitol on neutrophils isolated from the bone marrow of mice, there was a reduction on the chemotaxis of CXCL2/MIP-2 or LTB4-induced neutrophils and on calcium influx after pre-treatment with the compound at 3 or 10 μM. There was no change in CXCR2 expression by neutrophils treated with vestitol at 10 μM. These findings demonstrate that vestitol is a promising novel anti-inflammatory agent.
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903 SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Franchin
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900 SP, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Cólon
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900 SP, Brazil.
authors.forename: Fernanda V S
authors.initials: FV
authors.lastname: Castanheira
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903 SP, Brazil.
authors.forename: Marcos G
authors.initials: MG
authors.lastname: da Cunha
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903 SP, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bueno-Silva
authors.affiliation: "Luiz de Queiroz" College of Agriculture, University of São Paulo , Piracicaba, 13418-900 SP, Brazil.
authors.forename: Severino M
authors.initials: SM
authors.lastname: Alencar
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900 SP, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903 SP, Brazil.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Rosalen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001938:Brazil; D054360:Chemokine CXCL1; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011429:Propolis / Q000737:chemistry*; D000094162:Phytoalexins
chemical_list: D000893:Anti-Inflammatory Agents; D054360:Chemokine CXCL1; D005419:Flavonoids; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D011429:Propolis; C475829:CXCL1 protein, human; C515147:vestitol; D000094162:Phytoalexins