Oleocanthal Modulates LPS-Induced Murine Peritoneal Macrophages Activation via Regulation of Inflammasome, Nrf-2/HO-1, and MAPKs Signaling Pathways

J Agric Food Chem. 2019 May 15;67(19):5552-5559. doi: 10.1021/acs.jafc.9b00771. Epub 2019 May 1.

Abstract

The present study was designed to investigate the role of the canonical and noncanonical inflammasome, MAPKs and NRF-2/HO-1, signaling pathways involved in the antioxidant and anti-inflammatory activities of oleocanthal in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Isolated cells were treated with oleocanthal in the presence or absence of LPS (5 μg mL-1) for 18 h. Oleocanthal showed a potent reduction of reactive oxygen species (ROS) (25 μM, 50. 612 ± 0.02; 50 μM, 53. 665 ± 0.09; 100 μM, 52. 839 ± 0.02), nitrites (25 μM, 0.631 ± 0.07; 50 μM, 0.652 ± 0.07; 100 μM, 0.711 ± 0.08), and pro-inflammatory cytokines levels when compared with LPS-DMSO-treated control cells. In terms of enzymes protein expression, oleocanthal was able to downregulate iNOS (25 μM, 0.173 ± 0.02; 50 μM, 0.149 ± 0.01; 100 μM, 0.150 ± 0.01; p < 0.001), COX-2 (25 μM, 0.482 ± 0.08; 50 μM, 0.469 ± 0.05; 100 μM, 0.418 ± 0.06; p < 0.001), and mPGES-1 (25 μM, 0.185 ± 0.11; 50 μM, 0.218 ± 0.13; 100 μM, 0.161 ± 0.15; p < 0.001) as well as p38 (25 μM, 0.366 ± 0.11; 50 μM, 0.403 ± 0.13; 100 μM, 0.362 ± 0.15; p < 0.001), JNK (25 μM, 0.443 ± 0.11; 50 μM, 0.514 ± 0.13; 100 μM, 0.372 ± 0.15; p < 0.001), and ERK (25 μM, 0.294 ± 0.01; 50 μM, 0.323 ± 0.01; 100 μM, 0.274 ± 0.01; p < 0.001) protein phosphorylation, which was accompanied by an upregulation of Nrf-2 (25 μM, 1.57 ± 0.01; 50 μM, 1.54 ± 0.01; 100 μM, 1.63 ± 0.05; p < 0.05) and HO-1(25 μM, 2.12 ± 0,03; 50 μM, 2.24 ± 0.01; 100 μM, 1.92 ± 0.05; p < 0.01) expression in comparison with LPS-DMSO cells. Moreover, oleocanthal inhibited canonical and noncanonical inflammasome signaling pathways. Thus, oleocanthal might be a promising natural agent for future treatment of immune-inflammatory diseases.

Keywords: MAPKs; Nrf-2/HO-1; inflammasome; macrophages; oleocanthal.

MeSH terms

  • Aldehydes / pharmacology*
  • Animals
  • Cells, Cultured
  • Cyclopentane Monoterpenes
  • Female
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / immunology*
  • Inflammasomes / drug effects
  • Inflammasomes / genetics
  • Inflammasomes / immunology*
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology*
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / immunology*
  • Phenols / pharmacology*
  • Phosphorylation
  • Reactive Oxygen Species / immunology

Substances

  • Aldehydes
  • Cyclopentane Monoterpenes
  • Inflammasomes
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Phenols
  • Reactive Oxygen Species
  • oleocanthal
  • Heme Oxygenase-1