title: A new labdane diterpenoid with anti-inflammatory activity from Thuja orientalis.
abstract: ETHONOPHARMACOLOGICAL RELEVANCE: Thuja orientalis (L) ENDL (Cupressaceae) is an evergreen arbor that is distributed throughout Northeast Asia. This plant has been used as a traditional medicine for the treatment of various inflammatory diseases such as dermatitis, gout and chronic tracheitis.
  
  
  OBJECTIVE
  To isolate the active principles responsible for the anti-inflammatory activities of Thuja orientalis and to disclose their mechanism of action in lipopolysaccharide (LPS)-stimulated macrophages.
  
  
  METHODS
  The methanolic leaves and stem extracts of the Thuja orientalis were successively fractionated into EtOAc, n-BuOH and the remaining aqueous fractions. The EtOAc soluble fraction, which exhibited significant inhibitory activity on LPS-induced nitric oxide (NO) production, was followed by successive activity-guided chromatography to yield seven diterpenoids. The anti-inflammatory properties of active constituents were evaluated by RT-PCR, Western blotting and reporter gene assay in cell culture system.
  
  
  RESULTS
  A new labdane diterpene, 15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid (1), and six known diterpenoids (2-7) were isolated from the EtOAc extracts of Thuja orientalis. The isolated compounds 1-7 were evaluated for the inhibitory activity of LPS-induced NO production in RAW264.7 macrophage cells. Compound 1 was the most potent among the isolated compounds for the inhibition of LPS-induced NO production (IC501: 3.56μM). Compound 1 reduced the production of pro-inflammatory mediators and suppressed the expression of the inflammatory enzymes of iNOS and COX-2. In addition, compound 1 attenuated the LPS-induced transcriptional activity of NF-κB by the inhibition of inhibitory-κBα degradation, and suppressed the activity of extracellular signal regulated kinase (ERK).
  
  
  CONCLUSIONS
  This study demonstrates that a new labdane diterpene from Thuja orientalis inhibits the inflammatory responses by the suppression of NF-κB activity and ERK phosphorylation. This compound might be a valuable candidate for the development of anti-inflammatory drugs.
authors: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
authors: Tae-Hee
authors: TH
authors: Kim
authors: Hua
authors: H
authors: Li
authors: Qian
authors: Q
authors: Wu
authors: Hwa Jin
authors: HJ
authors: Lee
authors: Jae-Ha
authors: JH
authors: Ryu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029783:Thuja / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004224:Diterpenes; D008070:Lipopolysaccharides; D010936:Plant Extracts; C433017:labdane; D009569:Nitric Oxide; D015232:Dinoprostone