Abstract
We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-κB (NF-κB) nuclear translocation, inhibitory factor-κB (IκB) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating IκB-α phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-κB and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / pharmacology
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Cell Line
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Humans
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I-kappa B Proteins / metabolism
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Inflammation / immunology
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Inflammation / prevention & control
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Inula / metabolism
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lactones / pharmacology*
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Lipopolysaccharides
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Macrophages / enzymology
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Macrophages / metabolism*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase Type II / biosynthesis*
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Phosphorylation / drug effects
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Plant Extracts / pharmacology
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Proteolysis / drug effects
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Sesquiterpenes / pharmacology
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Sesquiterpenes, Eudesmane / pharmacology*
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Transcription Factor RelA / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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1-oxo-4aH-eudesma-5(6),11(13)-dien-12,8-olide
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Anti-Inflammatory Agents
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I-kappa B Proteins
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Lactones
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Lipopolysaccharides
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Plant Extracts
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RELA protein, human
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Sesquiterpenes
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Sesquiterpenes, Eudesmane
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Transcription Factor RelA
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Nitric Oxide
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Nitric Oxide Synthase Type II
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases