title: Extracellular signal-regulated kinase is a direct target of the anti-inflammatory compound amentoflavone derived from Torreya nucifera.
abstract: Amentoflavone is a biflavonoid compound with antioxidant, anticancer, antibacterial, antiviral, anti-inflammatory, and UV-blocking activities that can be isolated from Torreya nucifera, Biophytum sensitivum, and Selaginella tamariscina. In this study, the molecular mechanism underlying amentoflavone's anti-inflammatory activity was investigated. Amentoflavone dose dependently suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW264.7 cells stimulated with the TLR4 ligand lipopolysaccharide (LPS; derived from Gram-negative bacteria). Amentoflavone suppressed the nuclear translocation of c-Fos, a subunit of activator protein (AP)-1, at 60 min after LPS stimulation and inhibited the activity of purified and immunoprecipitated extracellular signal-regulated kinase (ERK), which mediates c-Fos translocation. In agreement with these results, amentoflavone also suppressed the formation of a molecular complex including ERK and c-Fos. Therefore, our data strongly suggest that amentoflavone's immunopharmacological activities are due to its direct effect on ERK.
authors: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Jueun
authors: J
authors: Oh
authors: Ho Sik
authors: HS
authors: Rho
authors: Yanyan
authors: Y
authors: Yang
authors: Ju Young
authors: JY
authors: Yoon
authors: Jongsung
authors: J
authors: Lee
authors: Yong Deog
authors: YD
authors: Hong
authors: Hyeon Chung
authors: HC
authors: Kim
authors: Sun Shim
authors: SS
authors: Choi
authors: Tae Woong
authors: TW
authors: Kim
authors: Song Seok
authors: SS
authors: Shin
authors: Jae Youl
authors: JY
authors: Cho
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D032490:Taxaceae / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D044946:Biflavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; C011164:amentoflavone; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone
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