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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 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 andmore » 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.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [5]
  1. Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714 (Korea, Republic of)
  2. Department of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of)
  3. Department of Marine Life Sciences, Jeju National University, Jeju 690-756 (Korea, Republic of)
  4. Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 (Korea, Republic of)
  5. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22215360
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 262; Journal 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); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL EFFECTS; DISULFIDES; GARLIC; INFLAMMATION; INHIBITION; LYMPHOKINES; MESSENGER-RNA; MONOCYTES; NERVOUS SYSTEM DISEASES; NITRIC OXIDE; PROSTAGLANDINS

Citation Formats

Park, Hye Young, Department of Pharmacy, Pusan National University, Busan 609-735, Kim, Nam Deuk, Kim, Gi-Young, Hwang, Hye Jin, Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714, Kim, Byung-Woo, Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714, Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714, Kim, Wun Jae, Choi, Yung Hyun, E-mail: choiyh@deu.ac.kr, Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, and Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714. Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.04.034.
Park, Hye Young, Department of Pharmacy, Pusan National University, Busan 609-735, Kim, Nam Deuk, Kim, Gi-Young, Hwang, Hye Jin, Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714, Kim, Byung-Woo, Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714, Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714, Kim, Wun Jae, Choi, Yung Hyun, E-mail: choiyh@deu.ac.kr, Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, & Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714. Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia. United States. doi:10.1016/J.TAAP.2012.04.034.
Park, Hye Young, Department of Pharmacy, Pusan National University, Busan 609-735, Kim, Nam Deuk, Kim, Gi-Young, Hwang, Hye Jin, Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714, Kim, Byung-Woo, Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714, Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714, Kim, Wun Jae, Choi, Yung Hyun, E-mail: choiyh@deu.ac.kr, Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, and Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714. Sun . "Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia". United States. doi:10.1016/J.TAAP.2012.04.034.
@article{osti_22215360,
title = {Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia},
author = {Park, Hye Young and Department of Pharmacy, Pusan National University, Busan 609-735 and Kim, Nam Deuk and Kim, Gi-Young and Hwang, Hye Jin and Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714 and Kim, Byung-Woo and Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714 and Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714 and Kim, Wun Jae and Choi, Yung Hyun, E-mail: choiyh@deu.ac.kr and Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 and Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714},
abstractNote = {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.},
doi = {10.1016/J.TAAP.2012.04.034},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 262,
place = {United States},
year = {2012},
month = {7}
}