Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis.
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 microg/mL), and also the luciferase activity in TNF-alpha-stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/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-kappaB sites in the iNOS promoter.
Paulino
Niraldo
N
Grupo de Pesquisa e Desenvolvimento de Biofármacos BIOFAR, Universidade do Sul de Santa Catarina, Tubarão/SC, Brazil. niraldo@unisul.br
Teixeira
Cristiane
C
Martins
Regiane
R
Scremin
Amarilis
A
Dirsch
Verena M
VM
Vollmar
Angelika M
AM
Abreu
Sheila R
SR
de Castro
Solange L
SL
Marcucci
Maria Cristina
MC
D000700:Analgesics / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D001938:Brazil; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use; D011429:Propolis / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D011429:Propolis; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse