Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway.

Abstract

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.

• Authors: K J Senthil Kumar, Han Wen Hsieh, Sheng-Yang Wang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 10 Issue 4 Pg. 385-92 (Apr 2010) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 20079881 (Publication Type: Journal Article)
• Copyright: Copyright 2009 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Cyclopentanes
• Lipopolysaccharides
• NF-kappa B
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• lucidone
• Nitric Oxide
• RNA
• Nitric Oxide Synthase Type II
• I-kappa B Kinase
• Mitogen-Activated Protein Kinases
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics, pharmacology)
• Biological Availability
• Blotting, Western
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Cyclopentanes (pharmacokinetics, pharmacology)
• Dinoprostone (antagonists & inhibitors, biosynthesis)
• Electrophoretic Mobility Shift Assay
• I-kappa B Kinase (antagonists & inhibitors)
• Inflammation (drug therapy, pathology)
• Lindera (chemistry)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• RNA (biosynthesis, isolation & purification)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (antagonists & inhibitors)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)