title: Curcumol exhibits anti-inflammatory properties by interfering with the JNK-mediated AP-1 pathway in lipopolysaccharide-activated RAW264.7 cells.
abstract: Curcumol is one of the major components of the essential oil of Rhizoma Curcumae, a common traditional Chinese medicine with anti-inflammatory properties. However, the anti-inflammatory activity and the underlying molecular mechanisms of this compound remain unclear. In the present study, the anti-inflammation effect of curcumol on lipopolysaccharide (LPS)-induced RAW264.7 cells is demonstrated along with its underlying mechanisms. We show that curcumol inhibits LPS-induced NO production by suppressing iNOS mRNA expression and protein level but not iNOS activity. Moreover, curcumol inhibits LPS-induced production of TNF-α, IL-1β and IL-6 at both the transcriptional and translational levels. Further investigations reveal that these effects mainly act via suppressing JNK-mediated AP-1 rather than the NF-κB pathway; these effects include a decrease in the phosphorylation level of JNK and a direct inhibition of the activity of p-JNK. These data provide scientific molecular evidence that curcumol may be a potential lead compound for a novel anti-inflammatory drug because of its inhibitory activity on the production of various inflammatory mediators.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Heilongjiang University of Chinese Medicine, Harbin 150040, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Chuanjie
authors.initials: C
authors.lastname: Zong
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Runlan
authors.initials: R
authors.lastname: Cai
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: yqi@implad.ac.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; C022801:curcumol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases
keywords: AP-1 (activator protein-1); Anti-inflammation; Curcumol; JNK (c-Jun N-terminal kinase); Lipopolysaccharide (LPS)