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기타논문
Date: April 2013

Journal: Neurochemical Research Volume 38, Issue 4, April 2013, Pages 807-814 , Doi: 10.1007/s11064-013-0983-6

2013 | A novel synthetic compound 4-Acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c] pyran-1,8-dione inhibits the production of nitric oxide and proinflammatory cytokines Via the NF-κB pathway in lipopolysaccharide-activated microglia cells…

Chung, H.-S.a, Kim, S.-N.a, Jeong, J.-H.b, Bae, H.a

Abstract

Previously, we discovered a new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8- dione (PPY), from Vitex rotundifolia L. and evaluated its anti-inflammatory and anti-asthmatic effects. In this study, we synthesized a new, modified compound 4-acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione (PPY-Br) based on the PPY skeleton and evaluated its anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglia. PPY-Br suppresses nitric oxide production, inducible nitric oxide synthase expression, and tumor necrosis factor-α and interleukin-6 production in LPS-activated BV-2 microglial cell line and mouse primary microglia. The effect of PPY-Br on the activation of nuclear factor (NF)-kappaB was examined to identify the mechanism involved. The LPS-induced translocation of NF-κB to the nucleus and phosphorylation of inhibitory-kappaB were almost completely blocked by PPY-Br. This study indicates that PPY-Br significantly attenuates the level of neurotoxic, proinflammatory mediators and proinflammatory cytokines via inhibition of the NF-κB signaling pathway. We suggest that PPY-Br presents a new candidate treatment for various neuro-inflammatory diseases. © 2013 Springer Science+Business Media New York.


Author keywords

4-Acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione; Lipopolysaccharide; Microglia; NF-κB; Nitric oxide


Indexed keywords

EMTREE drug terms: 4 acetyl 3 methyl 6 (2 bromophenyl)pyrano[3,4 c]pyran 1,8 dione; antiinflammatory agent; autacoid; cytokine; immunoglobulin enhancer binding protein; inducible nitric oxide synthase; interleukin 6; lipopolysaccharide; nitric oxide; tumor necrosis factor alpha; unclassified drug

EMTREE medical terms: animal cell; article; cell activation; cell nucleus; controlled study; cytokine production; cytokine release; drug structure; drug synthesis; metabolic inhibition; microglia; mouse; neurotoxicity; nonhuman; priority journal; protein analysis; protein expression; protein induction; protein phosphorylation; protein synthesis inhibition; protein transport; signal transduction

MeSH: Animals; Anti-Inflammatory Agents; Bicyclo Compounds, Heterocyclic; Cytokines; Interleukin-6; Lipopolysaccharides; Mice; Microglia; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Pyrones; Tumor Necrosis Factor-alpha
Medline is the source for the MeSH terms of this document.

Species Index: Vitex rotundifolia


Chemicals and CAS Registry Numbers: inducible nitric oxide synthase, 501433-35-8; nitric oxide, 10102-43-9;4-acetyl-3-methyl-6-(2-bromophenyl)pyrano(3,4-c)pyran-1,8-dione; Anti-Inflammatory Agents; Bicyclo Compounds, Heterocyclic; Cytokines; Interleukin-6; Lipopolysaccharides; NF-kappa B; Nitric Oxide, 10102-43-9; Nitric Oxide Synthase Type II, 1.14.13.39; Nos2 protein, mouse, 1.14.13.39; Pyrones; Tumor Necrosis Factor-alpha


ISSN: 03643190 CODEN: NEREDSource Type: Journal Original language: English
DOI: 10.1007/s11064-013-0983-6 PubMed ID: 23377856 Document Type: Article
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