β-Ionone attenuates LPS-induced pro-inflammatory mediators such as NO, PGE<sub>2</sub> and TNF-α in BV2 microglial cells via suppression of the NF-κB and MAPK pathway

Abstract

beta-Ionone, a precursor of carotenoids, possesses a variety of biological properties such as anti-cancerous, anti-mutagenic and anti-microbial activity. Nevertheless, anti-inflammatory effects of beta-ionone remain unknown. In this study, we investigated whether ION attenuates the expression of lipopolysaccharide (LPS)-induced pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E-2 (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha) in BV2 microglia cells. Our data showed that beta-ionone significantly inhibits secretion of NO, PGE(2) and TNF-alpha. beta-Ionone also inhibits the expression of inducible NO synthesis (iNOS), cyclooxygenase-2 (COX-2) and TNF-alpha protein and their mRNA in LPS-stimulated BV2 microglia cells. In addition, beta-ionone significantly reduced DNA-binding activity of nuclear factor-kappa B (NF-kappa B) through suppression of nuclear translocation of p50 and p65. We showed that NF-kappa B inhibitor N-acetyl-L-cysteine (NAC) effectively attenuates the expression of LPS-stimulated iNOS, COX-2 and TNF-alpha. We also found that LPS-induced NF-kappa B activation is significantly regulated through inhibition of Akt phosphorylation in the presence of beta-ionone. Finally, we showed that beta-ionone substantially inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, p38 and JNK, which are closely related to regulation of pro-inflammatory mediator secretion. Taken together, these data imply that beta-ionone regulates LPS-induced NF-kappa B-dependent inflammatory pathways through suppression of Akt and MAPK activation. (C) 2013 Elsevier Ltd. All rights reserved.