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

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 mu g mL(-1)) for 18 h. Oleocanthal showed a potent reduction of reactive oxygen species (ROS) (25 mu M, 50. 612 +/- 0.02; 50 mu M, 53. 665 +/- 0.09; 100 mu M, 52. 839 +/- 0.02), nitrites (25 mu M, 0.631 +/- 0.07; 50 mu M, 0.652 +/- 0.07; 100 mu M, 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 mu M, 0.173 +/- 0.02; 50 mu M, 0.149 +/- 0.01; 100 mu M, 0.150 +/- 0.01;p < 0.001), COX-2 (25 mu M, 0.482 +/- 0.08; 50 mu M, 0.469 +/- 0.05; 100 mu M, 0.418 +/- 0.06; p < 0.001), and mPGES-1 (25 mu M, 0.185 +/- 0.11; 50 mu M, 0.218 +/- 0.13; 100 mu M, 0.161 +/- 0.1S; p < 0.001) as well as p38 (25 mu M, 0.366 +/- 0.11; 50 mu M, 0.403 +/- 0.13; 100 mu M, 0.362 +/- 0.15; p < 0.001), JNK (25 mu M, 0.443 +/- 0.11; 50 mu M, 0.514 +/- 0.13; 100 mu M, 0.372 +/- 0.15; p < 0.001), and ERK (25 mu M, 0.294 +/- 0.01; 50 mu M, 0.323 +/- 0.01; 100 mu M, 0.274 +/- 0.01; p < 0.001) protein phosphorylation, which was accompanied by an upregulation of Nrf-2 (25 mu M, 1.57 +/- 0.01; 50 mu M, 1.54 +/- 0.01; 100 mu M, 1.63 +/- 0.05; p < 0.05) and HO-1(25 mu M, 2.12 +/- 0,03; 50 mu M, 2.24 +/- 0.01; 100 mu M, 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.