Abstract
Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection (i. p. ) of G1 inhibited acetic acid-induced abdominal constrictions with an ID50 = 0.75 ± 0.05 mg/kg, and in the formalin test the ID50 values were 0.85 ± 0.07 mg/kg and 13.88 ± 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered i. p. and of 36 % after 15 min by the oral route (o. r. ). When the inflammatory agent was complete Freund’s adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID50 values were 1.09 ± 0.08 mg/kg (i. p. ) and 10.00 ± 0.90 mg/kg (o. r. ). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC50 values of 0.72 ± 0.08 mg/kg and 4.17 ± 0.50 mg/kg, by i. p. or o. r. administration, with a preferential migration of polymorphonuclear neutrophils. In vitro , G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC50 = 41.60 μg/mL), and also the luciferase activity in TNF-α-stimulated HEK 293 cells transfected with NF-κB-luciferase reporter gene driven by the nuclear factor κB (NF-κB) (IC50 = 200 μg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-κB sites in the iNOS promoter.
Abbreviations
CFA:complete Freund adjuvant
COX-2:inducible isoform of cyclooxygenase
Indo:Indomethacin
iNOS:inducible nitric oxide synthase
LPS:Lipopolysaccharide
MI:maximal inhibition
MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
NF-κB:nuclear factor κB
NO:nitric oxide
TMB:3,3′,5,5′-tetramethylbenzidine
Key words
Typified propolis - analgesic effect - anti-inflammatory effect - NF-κB factor - nitric oxide
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niraldo@unisul.br
