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Toxicol Appl Pharmacol ; 371: 3-11, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30943385

ABSTRACT

Trans-4-methoxycinnamaldehyde (MCD) was isolated from the rhizomes of Etlingera pavieana (Pierre ex Gagnep.) R.M.Sm. MCD shows anti-inflammatory effects. However, the molecular mechanism underlying its anti-inflammatory action has not been described. In this study, we investigated this mechanism in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and found MCD significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in a concentration-dependent manner. MCD could decrease LPS- and Pam3CSK4- induced the expressions of both iNOS and COX-2. The phosphorylation of inhibitory κB (IκB) and translocation of nuclear factor-κB (NF-κB) p65 subunit into the nucleus were also inhibited by MCD. Moreover, MCD suppressed LPS-induced phosphorylation of JNK except for ERK and p38 mitogen-activated protein kinases (MAPKs). Moreover, MCD significantly reduced ethyl phenylpropiolate-induced ear edema and carrageenan-induced paw edema in rat models. These findings indicated MCD has anti-inflammatory activity by inhibiting the production of NO and PGE2 by blocking NF-κB and JNK/c-Jun signaling pathways. Collectively, these data suggest that MCD could be developed as a novel therapeutic agent for inflammatory disorders.


Subject(s)
Acrolein/analogs & derivatives , Anti-Inflammatory Agents/pharmacology , Edema/prevention & control , JNK Mitogen-Activated Protein Kinases/metabolism , Macrophage Activation/drug effects , Macrophages/drug effects , NF-kappa B/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-jun/metabolism , Zingiberaceae , Acrolein/isolation & purification , Acrolein/pharmacology , Alkynes , Animals , Anti-Inflammatory Agents/isolation & purification , Carrageenan , Cyclooxygenase 2/metabolism , Disease Models, Animal , Edema/chemically induced , Edema/immunology , Edema/metabolism , Endotoxins/pharmacology , Humans , Macrophages/enzymology , Macrophages/immunology , Male , Mice , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Plant Extracts/isolation & purification , RAW 264.7 Cells , Rats, Sprague-Dawley , Rhizome , Signal Transduction , Zingiberaceae/chemistry
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