title: Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production.
abstract: OBJECTIVE
  Extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delineated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E2 (PGE2) and on the expression of the cyclooxygenase isoforms, COX-1 and COX-2, in various human cell types.
  
  
  METHODS
  Monocytes from human peripheral blood (HM), fibroblasts from rheumatoid arthritis synovial tissue (RASF), human neonatal foreskin fibroblasts (HFF), and the histiocytic cell line U937 were cultured for designated time periods with or without lipopolysaccharide (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF, the ethyl acetate (EA) extract of TWHF, a purified diterpenoid component of TWHF (triptolide), dexamethasone, and indomethacin. Culture supernatants were harvested for PGE2 content assays. Total RNA was extracted from the cells and analyzed for COX-1 and COX-2 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting.
  
  
  RESULTS
  Both the T2 and EA extracts inhibited PGE2 synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE2 production in U937 cells that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE2, at the same inhibitory concentration as seen with the EA extract. The effects of T2, EA, and triptolide paralleled the inhibitory action of dexamethasone.
  
  
  CONCLUSIONS
  The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE2 production in a variety of human cells by blocking the up-regulation of COX-2.
authors.affiliation: University of Texas Southwestern Medical Center at Dallas, 75235-8884, USA.
authors.forename: X
authors.initials: X
authors.lastname: Tao
authors.forename: H
authors.initials: H
authors.lastname: Schulze-Koops
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.forename: Y
authors.initials: Y
authors.lastname: Mao
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002725:Chloroform; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004852:Epoxy Compounds; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides; D016403:Lymphoma, Large B-Cell, Diffuse; D008565:Membrane Proteins; D000432:Methanol; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D010616:Phenanthrenes; D010936:Plant Extracts / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D029757:Tripterygium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
chemical_list: D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D007376:Interleukin-2; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010616:Phenanthrenes; D010936:Plant Extracts; D012333:RNA, Messenger; C001899:triptolide; C007650:ethyl acetate; D002725:Chloroform; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000432:Methanol