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
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.
Keywords4-Acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione Nitric oxide Microglia Lipopolysaccharide NF-κB
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government [MEST] (No. 2012-0005755) and by a grant from the Kyung Hee University in 2007. (KHU-20070627).
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