title: Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia.
abstract: Diallyl disulfide (DADS), a main organosulfur component responsible for the diverse biological effects of garlic, displays a wide variety of internal biological activities. However, the cellular and molecular mechanisms underlying DADS' anti-inflammatory activity remain poorly understood. In this study, therefore, the anti-inflammatory effects of DADS were studied to investigate its potential therapeutic effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that pretreatment with DADS prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in a dose-dependent manner. The inhibition was associated with down-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. DADS also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1) by suppressing the expression of mRNAs for these proteins. The mechanism underlying this protective effect might be related to the inhibition of nuclear factor-kappaB, Akt and mitogen-activated protein kinase signaling pathway activation in LPS-stimulated microglial cells. These findings indicated that DADS is potentially a novel therapeutic candidate for the treatment of various neurodegenerative diseases.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Park
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Wun Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000498:Allyl Compounds; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004220:Disulfides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C028009:diallyl disulfide; D012313:RNA; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone