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

Phytomedicine. 2016 Dec 1;23(13):1583-1590. doi: 10.1016/j.phymed.2016.09.009. Epub 2016 Sep 28.

Abstract

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.

Keywords: Brazilian red propolis; Cytokines; Inflammation; Neutrophils.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Brazil
  • Cell Movement / drug effects
  • Chemokine CXCL2 / metabolism
  • Chemotaxis, Leukocyte / drug effects
  • Cytokines / metabolism
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Mice, Inbred BALB C
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Propolis / pharmacology*
  • Receptors, CXCR3 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Cxcr3 protein, mouse
  • Cytokines
  • Receptors, CXCR3
  • Propolis