title: Mechanisms by which licochalcone e exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages.
abstract: In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5-2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5-7.5 μmol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1β and tumor necrosis factor-α; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of κB (IκB) kinase-αβ and IκBα, degradation of IκBα, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-κB; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-κB and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. jyoon@hallym.ac.kr.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Lee
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Do Young
authors.initials: DY
authors.lastname: Lim
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004423:Ear / Q000473:pathology; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047188:Chalcones; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C520147:licochalcone E; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate