Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-kappaB and MAPKs signaling pathways.
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.
Senthil Kumar
K J
KJ
Department of Forestry, National Chung-Hsing University, Taichung, Taiwan.
Wang
Sheng-Yang
SY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018929:Cell Culture Techniques; D052246:Cyclooxygenase 2 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D003517:Cyclopentanes / Q000302:isolation & purification / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D015870:Gene Expression; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D027443:Lindera / Q000737:chemistry; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D003517:Cyclopentanes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C529637:lucidone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone