title: N-trans-feruloyltyramine inhibits LPS-induced NO and PGE2 production in RAW 264.7 macrophages: Involvement of AP-1 and MAP kinase signalling pathways.
abstract: Mitogen-activated protein kinase (MAPK) signalling pathway can regulate inflammatory and immune responses. N-trans-feruloyltyramine (FLA) is an active phenylpropanoid compound. It possesses antioxidant, antimicrobial, anti-melanogenesis, and anticancer activities. However, the precise molecular mechanisms underlying FLA modulation of cytokine expression in LPS-stimulated RAW 264.7 macrophages have not been fully investigated. In this study, we examined the mechanisms underlying the immunomodulative effects of FLA isolated from Arcangelisia gusanlung. FLA strongly suppressed mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), but not tumor necrosis factor (TNF)-α, thereby inhibiting the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, FLA also inhibited nuclear translocation of activation protein (AP)-1, and simultaneously decreased the expression and phosphorylation of the c-Jun N-terminal kinase (JNK) protein. These results suggest that the anti-inflammatory effects of FLA might be attributed to downregulation of COX-2 and iNOS via suppression of AP-1 and the JNK signalling pathway in RAW 264.7 macrophages.
authors.affiliation: Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Yunyao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100193, China; School of Medicine, China Three Gorges University, Yichang 443002, China. Electronic address: yulingling@ctgu.edu.cn.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea. Electronic address: mhwang@kangwon.ac.kr.
authors.forename: Myeong-Hyeon
authors.initials: MH
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D016207:Cytokines; D008070:Lipopolysaccharides; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C074004:feruloyltyramine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D014439:Tyramine
keywords: Anti-inflammatory; Cyclooxygenase-2; Inducible nitric oxide synthase; Lipopolysaccharide; N-trans-feruloyltyramine