title: Aged red garlic extract suppresses nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages through inhibition of NF-κB.
abstract: Lipopolysaccharides (LPS) activate nuclear factor kappa B (NF-κB), a transcription factor that is involved in inflammatory response. The pathways that activate NF-κB can be modulated by phytochemicals derived from garlic. We recently demonstrated that aged red garlic extract (ARGE), a new formulation of garlic, decreases nitric oxide (NO) generation by upregulating of heme oxygenase-1 (HO-1) in RAW 264.7 cells activated by LPS. However, the effects of ARGE on LPS-induced NF-κB activation are unknown. This study was performed to evaluate whether ARGE regulates LPS-induced NO production by modulation of NF-κB activation in macrophages. The inhibition of NF-κB by Bay 11-7085, an inhibitor of NF-κB, decreased LPS-induced NO production. ARGE treatment markedly reduced LPS-induced NO production and NF-κB nuclear translocation. ARGE downregulated expression of inducible nitric oxide synthase (iNOS) and upregulated expression of HO-1, a cytoprotective and anti-inflammatory protein. However, Bay 11-7085 only reduced iNOS expression. The NO production and iNOS expressions upregulated by suppression of HO-1 were suppressed by treatment with ARGE and Bay 11-7085. These results show that ARGE reduces LPS-induced NO production in macrophages through inhibition of NF-κB nuclear translocation and HO-1 activation. Compared to Bay 11-7085, ARGE may enhance anti-inflammatory effects by controlling other anti-inflammatory signals as well as regulation of NF-κB.
authors.affiliation: 1 Department of Physiology, Institute of Health Sciences, Gyeongsang National University School of Medicine , Jinju, Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Yi-Yeong
authors.initials: YY
authors.lastname: Jeong
authors.forename: Sunkyu
authors.initials: S
authors.lastname: Han
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Shin
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kang
authors.forename: Nak-Ju
authors.initials: NJ
authors.lastname: Sung
authors.forename: Dawon
authors.initials: D
authors.lastname: Kang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005737:Garlic / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1
keywords: NF-κB; anti-inflammatory; garlic; nitric oxide