PMID- 22564536 OWN - NLM STAT- MEDLINE DCOM- 20121009 LR - 20161125 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 262 IP - 2 DP - 2012 Jul 15 TI - Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia. PG - 177-84 LID - 10.1016/j.taap.2012.04.034 [doi] AB - 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 E(2) (PGE(2)) 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-1beta (IL-1beta), tumor necrosis factor (TNF)-alpha, 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Park, Hye Young AU - Park HY AD - Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714, Republic of Korea. FAU - Kim, Nam Deuk AU - Kim ND FAU - Kim, Gi-Young AU - Kim GY FAU - Hwang, Hye Jin AU - Hwang HJ FAU - Kim, Byung-Woo AU - Kim BW FAU - Kim, Wun Jae AU - Kim WJ FAU - Choi, Yung Hyun AU - Choi YH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120504 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Allyl Compounds) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Disulfides) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 5HI47O6OA7 (diallyl disulfide) RN - 63231-63-0 (RNA) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Allyl Compounds/*pharmacology MH - Blotting, Western MH - Cell Survival/drug effects MH - Chemokine CCL2/biosynthesis/genetics MH - Cyclooxygenase 2/*biosynthesis/genetics MH - Dinoprostone/*metabolism MH - Disulfides/*pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Interleukin-1beta/biosynthesis/genetics MH - Lipopolysaccharides/pharmacology MH - Microglia/*drug effects/enzymology/immunology MH - Neurodegenerative Diseases/enzymology/*immunology MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase Type II/*biosynthesis/genetics MH - RNA/chemistry/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics EDAT- 2012/05/09 06:00 MHDA- 2012/10/10 06:00 CRDT- 2012/05/09 06:00 PHST- 2011/12/23 00:00 [received] PHST- 2012/04/22 00:00 [revised] PHST- 2012/04/26 00:00 [accepted] PHST- 2012/05/09 06:00 [entrez] PHST- 2012/05/09 06:00 [pubmed] PHST- 2012/10/10 06:00 [medline] AID - S0041-008X(12)00185-8 [pii] AID - 10.1016/j.taap.2012.04.034 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2012 Jul 15;262(2):177-84. doi: 10.1016/j.taap.2012.04.034. Epub 2012 May 4.