title: Anti-inflammatory mechanism of 15,16-epoxy-3α-hydroxylabda-8,13(16),14-trien-7-one via inhibition of LPS-induced multicellular signaling pathways.
abstract: Phytochemical investigation of Leonurus japonicus has led to the isolation of a labdane diterpene derivative, 15,16-epoxy-3α-hydroxylabda-8,13(16),14-trien-7-one (1), which was tested for its in vitro anti-inflammatory effects. The results demonstrated that 1 exhibits an inhibitory effect on LPS-stimulated RAW 264.7 macrophages. The anti-inflammatory action shown by 1 suppressed LPS-induced NF-κB activation, resulting in the down-regulation of iNOS and COX-2 protein expression, attributable to the inhibitory action of LPS-induced NO and PGE(2) production. Compound 1 inhibited LPS-induced phosphorylation and the degradation of inhibitory kappa B (IκBα) and decreased the nuclear translocation of p50 and p65. In addition, 1 exhibited an inhibitory effect on LPS-induced NF-κB-DNA and AP-1-DNA binding activity, using an electrophoretic mobility shift assay with NF-κB- and AP-1-specific (32)P-labeled probes. The LPS-induced mitogen-activated protein kinases (p-JNK, p-p38, and p-ERK) and p-Akt were inhibited after 30 and 10 min of LPS stimulation, respectively. In addition, TNF-α production was suppressed by 1.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Salman
authors.initials: S
authors.lastname: Khan
authors.forename: Omer
authors.initials: O
authors.lastname: Shehzad
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Jin
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Sa Wang
authors.initials: SW
authors.lastname: Baek
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Kim
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D007723:Korea; D019686:Lamiaceae / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D018517:Plant Roots / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: C570753:15,16-epoxy-3alpha-hydroxylabda-8,13(16),14-trien-7-one; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020929:Mitogen-Activated Protein Kinase Kinases