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

• Published in: Toxicology and applied pharmacology 2019-05, Vol.371, p.3-11
• Main Authors: Srisook, Klaokwan, Mankhong, Sakulrat, Chiranthanut, Natthakarn, Kongsamak, Kittiya, Kitwiwat, Na-thanit, Tongjurai, Patsara, Aramsangtienchai, Pornpun
• Format: Article
• Language: English
• Subjects: Acrolein - analogs & derivatives; Acrolein - isolation & purification; Acrolein - pharmacology; Alkynes; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Carrageenan; COX-2; Cyclooxygenase 2 - metabolism; Disease Models, Animal; Edema - chemically induced; Edema - immunology; Edema - metabolism; Edema - prevention & control; Endotoxins - pharmacology; Humans; iNOS; JNK Mitogen-Activated Protein Kinases - metabolism; Macrophage Activation - drug effects; Macrophages - drug effects; Macrophages - enzymology; Macrophages - immunology; Male; Mice; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; PGE2; Phosphorylation; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-jun - metabolism; Rats, Sprague-Dawley; RAW 264.7 Cells; Rhizome; Signal Transduction; Trans-4-methoxycinnamaldehyde; Zingiberaceae - chemistry
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2019.03.026

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. •Trans-4-methoxycinnamaldehyde (MCD) was isolated from Etlingera pavieana.•MCD inhibited NO, PGE2 and TNF-α production in a concentration-dependent manner.•MCD inhibited the phosphorylation of IκB and translocation of NF-κB p65 subunit.•MCD suppressed phosphorylation of JNK but not ERK and p38 MAPK.•MCD inhibited inflammatory response in in vivo animal models.