title: Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation.
abstract: BACKGROUND
  Korean red ginseng (KRG) is a traditional herbal medicine made by steaming and drying the fresh ginseng, leading to chemical transformation of some components by heat. It ameliorates various inflammatory diseases and strengthens the endocrine, immune, and central nervous systems. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumorigenesis.
  
  
  OBJECTIVE
  In this study we examined the effects and the mechanism underlying Korean red ginseng water extract (KRG-WE) inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells.
  
  
  METHODS
  The effect of the KRG on suppression of hypoxia-induced COX-2 in A549 cells were determined by Western blot and/or qRT-PCR. The anti-invasive effect of KRG-WE was evaluated on A549 cells using matrigel invasion assay. The activation of glucocorticoid receptor (GR) and sirtuin1 (Sirt1) was examined by using specific inhibitors.
  
  
  RESULTS
  We first observed that hypoxia induced COX-2 protein and mRNA levels and promoter activity were suppressed by KRG-WE. Second, we observed that hypoxia-induced cell migration is dramatically reduced by KRG-WE. Third, we found that the effect of KRG-WE was not antagonized by the GR antagonist RU486 implying that the effect is mediated other than GR pathway. Finally, we demonstrated that inhibition of Sirt1 abolished the effect of KRG-WE on hypoxia-induced COX-2 suppression and cell-invasion indicating that the suppression is mediated by Sirt1.
  
  
  CONCLUSIONS
  Taken together, KRG-WE inhibits the hypoxic induction of COX-2 expression and cell invasion through Sirt1 activation. Our results imply that KRG-WE could be effective for suppression of inflammation under hypoxia.
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Korea; Department of Sports Medicine, College of Health Science, Cheongju University, Cheongju 363-764, Korea.
authors.forename: Wonchung
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Korea.
authors.forename: Myeong Kuk
authors.initials: MK
authors.lastname: Shim
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, Chungju 380-701, Korea.
authors.forename: Sikwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Korea. Electronic address: yjlee@sejong.ac.kr.
authors.forename: YoungJoo
authors.initials: Y
authors.lastname: Lee
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D015735:Mifepristone; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D010936:Plant Extracts; D015735:Mifepristone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Cyclooxygenase-2; Hypoxia; Red ginseng extract; Sirtuin1