Anti-inflammatory effects of trans-1,3-diphenyl-2,3-epoxypropane-1-one mediated by suppression of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages

Abstract

To assess the potential therapeutic properties of trans-1,3-diphenyl-2,3-epoxypropane-1-one (DPEP), its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E-2 (PGE(2)). Additionally, DPEP suppressed the production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6. We investigated the mechanism by which DPEP inhibits NO and PGE(2) by examining the level of nuclear factor-kappa B (NF-kappa B) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signaling pathway in RAW 264.7 cells. DPEP inhibited LPS-induced phosphorylation of ERK, JNK, and p38. Furthermore, DPEP inhibited the LPS-induced phosphorylation of inhibitor kappa B (I kappa B)-alpha and NF-kappa B p50. Taken together, the results of this study demonstrate that DPEP inhibits LPS-stimulated inflammation by blocking the NF-kappa B and MAPK pathways in macrophages. (c) 2012 Elsevier Ltd. All rights reserved.