Anti-inflammatory effect of trans-4-methoxycinnamaldehyde from Etlingera pavieana in LPS-stimulated macrophages mediated through inactivation of NF-κB and JNK/c-Jun signaling pathways and in rat models of acute inflammation

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 E-2 (PGE(2)) 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 kappa B (I kappa B) and translocation of nuclear factor-kappa B (NF-kappa B) 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 carrageenaninduced paw edema in rat models. These findings indicated MCD has anti-inflammatory activity by inhibiting the production of NO and PGE(2) by blocking NF-kappa B and JNK/c-Jun signaling pathways. Collectively, these data suggest that MCD could be developed as a novel therapeutic agent for inflammatory disorders.