A sesquiterpenol extract potently suppresses inflammation in macrophages and mice skin and prevents chronic liver damage in mice through JNK-dependent HO-1 expression

摘要

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 Crypiomeria japonica (Taxodiaceae) wood extract. BSL markedly suppressed TNF-alpha 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-kappa B and mitogen-activated protein kinase signaling pathways, however, was not responsive to BSL treatment. A BSL-enriched extract (BSL-E; 10 mg/kg) significantly prevented CCl4-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