title: β-Ionone attenuates LPS-induced pro-inflammatory mediators such as NO, PGE2 and TNF-α in BV2 microglial cells via suppression of the NF-κB and MAPK pathway.
abstract: β-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 β-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 E2 (PGE2) and tumor necrosis factor-α (TNF-α) in BV2 microglia cells. Our data showed that β-ionone significantly inhibits secretion of NO, PGE2 and TNF-α. β-Ionone also inhibits the expression of inducible NO synthesis (iNOS), cyclooxygenase-2 (COX-2) and TNF-α protein and their mRNA in LPS-stimulated BV2 microglia cells. In addition, β-ionone significantly reduced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of nuclear translocation of p50 and p65. We showed that NF-κB inhibitor N-acetyl-L-cysteine (NAC) effectively attenuates the expression of LPS-stimulated iNOS, COX-2 and TNF-α. We also found that LPS-induced NF-κB activation is significantly regulated through inhibition of Akt phosphorylation in the presence of β-ionone. Finally, we showed that β-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 β-ionone regulates LPS-induced NF-κB-dependent inflammatory pathways through suppression of Akt and MAPK activation.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Kang
authors.forename: Rajapaksha Gendara Prasad Tharanga
authors.initials: RG
authors.lastname: Jayasooriya
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D045792:Norisoprenoids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D045792:Norisoprenoids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C008157:beta-ionone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone