Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis

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 ID 50 = 0.75 ± 0.05 mg/kg, and in the formalin test the ID 50 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 ID 50 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 IC 50 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 (IC 50 = 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) (IC 50 = 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.