title: A sesquiterpenol extract potently suppresses inflammation in macrophages and mice skin and prevents chronic liver damage in mice through JNK-dependent HO-1 expression.
abstract: This study aimed to elucidate the anti-inflammatory and hepatoprotective bioactivities of a sesquiterpenol, (1S,6R)-2,7(14),10-bisabolatrien-1-ol-4-one (BSL), isolated from Cryptomeria japonica (Taxodiaceae) wood extract. BSL markedly suppressed TNF-α and IL-6 secretion, PGE(2) production, and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-stimulated mouse macrophages. BSL also potently inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced protein levels of nitrotyrosine and COX-2 in mouse skin with dermatitis. Conversely, the stress protein heme oxygenase-1 (HO-1) was found upregulated in the same BSL-treated macrophages, probably through activation of the JNK-dependent pathway. LPS-induced activation of NF-κB and mitogen-activated protein kinase signaling pathways, however, was not responsive to BSL treatment. A BSL-enriched extract (BSL-E; 10mg/kg) significantly prevented CCl(4)-induced chronic liver injury, lipid accumulation, and cell necrosis and inhibited aminotransferase activities and iNOS and COX-2 overexpression in mice liver tissues, an effect comparable with that of silymarin, a hepatoprotective drug.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC. lfshyur@ccvax.sinica.edu.tw
authors.forename: Lie-Fen
authors.initials: LF
authors.lastname: Shyur
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Huang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Hsu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Shiaw-Der
authors.initials: SD
authors.lastname: Yang
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D032485:Cryptomeria / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003872:Dermatitis / Q000188:drug therapy; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008107:Liver Diseases / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology; D012867:Skin / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: C442121:2,7(14),10-bisabolatrien-1-ol-4-one; D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012717:Sesquiterpenes; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate