Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia
- Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714 (Korea, Republic of)
- Department of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of)
- Department of Marine Life Sciences, Jeju National University, Jeju 690-756 (Korea, Republic of)
- Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 (Korea, Republic of)
- Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of)
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{sub 2} (PGE{sub 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-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. -- Highlights: ► DADS attenuates production of NO and PGE2 in LPS-activated BV2 microglia. ► DADS downregulates levels of iNOS and COX-2. ► DADS inhibits production and expression of inflammatory cytokines and chemokine. ► DADS exhibits these effects by suppression of NF-κB, PI3K/Akt and MAPKs pathways.
- OSTI ID:
- 22215360
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 262, Issue 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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