Abstract
The anti-inflammatory mechanism of lucidone isolated from the fruits of Lindera erythrocarpa Makino was investigated. Our data indicate that lucidone significantly inhibits the production of NO and PGE(2) autacoids in LPS-induced RAW 264.7 murine macrophage cells. Moreover, it also notably decreased the secretion of tumor necrosis factor-alpha (TNF-alpha). Consistent with these observations, the mRNA and protein expression levels of iNOS and COX-2 were also inhibited by lucidone in a dose-dependent manner. Lucidone also reduced the translocation of NF-kappaB induced by LPS, which is associated with the prevention of the degradation of I-kappaB, and subsequently decreased p65/p50 protein levels in the nucleus. Lucidone also inhibited NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. In addition, lucidone inhibited JNK and p38MAPKs signals, which are the most significant signals involved in NO, PGE(2) and TNF-alpha production; NF-kappaB/AP-1 activation was also inhibited by lucidone. Taken together, the anti-inflammatory activity of lucidone might be caused by the inhibition of iNOS and COX-2 expressions through downregulation of NF-kappaB and AP-1 binding.
MeSH terms
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Animals
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Anti-Inflammatory Agents / isolation & purification
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Anti-Inflammatory Agents / pharmacology*
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Cell Culture Techniques
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Cyclooxygenase 2 Inhibitors / isolation & purification
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Cyclopentanes / isolation & purification
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Cyclopentanes / pharmacology*
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Dinoprostone / biosynthesis
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Gene Expression
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Lindera / chemistry
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Lipopolysaccharides
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Macrophages / drug effects*
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Macrophages / metabolism
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Male
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Mice
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B p50 Subunit / metabolism
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Protein Transport / drug effects
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RNA, Messenger / metabolism
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Signal Transduction / drug effects
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Transcription Factor AP-1 / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
Substances
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Anti-Inflammatory Agents
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Cyclooxygenase 2 Inhibitors
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Cyclopentanes
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Lipopolysaccharides
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NF-kappa B
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NF-kappa B p50 Subunit
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Plant Extracts
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RNA, Messenger
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Transcription Factor AP-1
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Tumor Necrosis Factor-alpha
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lucidone
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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 Kinases
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p38 Mitogen-Activated Protein Kinases
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Dinoprostone