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Main pathways of action of Brazilian red propolis on the modulation of neutrophils migration in the inflammatory process

Bueno-Silva, Bruno, Franchin, Marcelo, Alves, Claudiney de Freitas, Denny, Carina, Colón, David Fernando, Cunha, Thiago Mattar, Alencar, Severino Matias, Napimoga, Marcelo Henrique, Rosalen, Pedro Luiz
Phytomedicine 2016 v.23 no.13 pp. 1583-1590
CXCR2 receptor, anti-inflammatory activity, biochemical pathways, calcium, cell movement, cell viability, chemokine CXCL2, chemotaxis, inflammation, interleukin-1beta, mechanism of action, microscopy, neutrophils, propolis, rolling, tumor necrosis factor-alpha
Background: Brazilian propolis is popularly used as treatment for different diseases including the ones with inflammatory origin. Brazilian red propolis chemical profile and its anti-inflammatory properties were recently described however, its mechanism of action has not been investigated yet.Aim: Elucidate Brazilian red propolis major pathways of action on the modulation of neutrophil migration during the inflammatory process.Methods: The ethanolic extract of propolis (EEP) activity was investigated for neutrophil migration into the peritoneal cavity, intravital microscopy (rolling and adhesion of leukocytes), quantification of cytokines TNF-α, IL-1β and chemokines CXCL1/KC, CXCL2/MIP-2, neutrophil chemotaxis induced by CXCL2/MIP-2, calcium influx and CXCR2 expression on neutrophils.Results: EEP at 10mg/kg prevented neutrophil migration into peritoneal cavity (p < 0.05), reduced leukocyte rolling and adhesion on the mesenteric microcirculation (p < 0.05) and inhibited the release TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 (p < 0.05). EEP at 0.01, 0.1 and 1µg/ml reduced the CXCL2/MIP-2-induced neutrophils chemotaxis (p < 0.05) without affect cell viability (p > 0.05).EEP at 1µg/ml decreased the calcium influx induced by CXCL2/MIP-2 (p<0.05). On the other hand, none of EEP concentrations tested altered CXCR2 expression by neutrophils (p>0.05).Conclusion: Brazilian red propolis appears as a promising anti-inflammatory natural product which mechanism seems to be by reducing leukocyte rolling and adhesion; TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 release; CXCL2/MIP-2-induced chemotaxis and calcium influx.