Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway.
Here, we investigated the anti-inflammatory activity of lucidone, a phytocompound isolated from the fruits of Lindera erythrocarpa Makino, against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice. Male ICR mice were injected intraperitoneally with LPS (5 microg/kg), and the effects of pretreatment with various concentrations of lucidone (50-200 mg/kg) for 12h on the formation of nitric oxide (NO), prostaglandin-E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) were analyzed. Lucidone inhibited the production of NO, PGE(2) and TNF-alpha production in LPS-induced mice, and also induced mRNA and protein levels of inducible nitric oxide synthase (iNOS), and cyclooxigenase-2 (COX-2). The two common response elements of the iNOS and COX-2 genes are nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). NF-kappaB nuclear translocation and DNA binding were inhibited by lucidone in the LPS-induced mice. Moreover, lucidone decreased the expression and phosphorylation of c-Jun N-terminal kinase (JNK) protein thereby causing the subsequent inhibition of AP-1 activity. Finally, our results indicated that lucidone was able to block mitogen-activated protein kinases activity and its downstream signaling activation of NF-kappaB and AP-1. We thus conclude that lucidone exerts its anti-inflammatory effects in mice by inhibiting the expression of pro-inflammatory factors and their related signaling pathways.
Senthil Kumar
K J
KJ
Core Laboratory of Plant Metabolomics in Biotechnology Centre, Department of Forestry, National Chung Hsing University, Kou Kung Road, Taichung 402, Taiwan.
Hsieh
Han Wen
HW
Wang
Sheng-Yang
SY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D015153:Blotting, Western; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003517:Cyclopentanes / Q000493:pharmacokinetics / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D027443:Lindera / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D003517:Cyclopentanes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C529637:lucidone; D009569:Nitric Oxide; D012313:RNA; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone