Abstract
Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology
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Cyclooxygenase 2 / metabolism
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Cytokines / metabolism
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Inflammation / chemically induced
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Inflammation Mediators
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Mice
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Molecular Structure
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NF-kappa B / antagonists & inhibitors*
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Phosphorylation / drug effects
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Sesquiterpenes / chemistry
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Sesquiterpenes / isolation & purification*
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Sesquiterpenes / pharmacology*
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Signal Transduction / drug effects
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Anti-Inflammatory Agents
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Cytokines
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Inflammation Mediators
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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RELA protein, human
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Sesquiterpenes
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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chlojaponilactone B
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Nitric Oxide
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NOS2 protein, human
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2