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Neurochem Res. 2013 Apr;38(4):807-14. doi: 10.1007/s11064-013-0983-6. Epub 2013 Feb 2.

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.

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1
Department of Physiology, College of Oriental Medicine, Kyung Hee University, #1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.

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.

PMID:
23377856
DOI:
10.1007/s11064-013-0983-6
[Indexed for MEDLINE]
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