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

Hwan Suck Chung, Sae Noon Kim, Jin Hyun Jeong, Hyunsu Bae

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)807-814
Number of pages8
JournalNeurochemical Research
Volume38
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

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Microglia
Lipopolysaccharides
Nitric Oxide
Cytokines
Anti-Inflammatory Agents
Vitex
Anti-Asthmatic Agents
Phosphorylation
Nitric Oxide Synthase Type II
Skeleton
Interleukin-6
Tumor Necrosis Factor-alpha
Chemical activation
Cells
Cell Line
4-acetyl-3-methyl-6-(2-bromophenyl)pyrano(3,4-c)pyran-1,8-dione

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "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",
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.",
author = "Chung, {Hwan Suck} and Kim, {Sae Noon} and Jeong, {Jin Hyun} and Hyunsu Bae",
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T1 - 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

AU - Chung, Hwan Suck

AU - Kim, Sae Noon

AU - Jeong, Jin Hyun

AU - Bae, Hyunsu

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N2 - 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.

AB - 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.

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