title: Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4/7-JNK and p38 MAPK signaling pathways in HepG2 cells.
abstract: BACKGROUND
  The induction of cellular defensive genes such as phase II detoxifying and antioxidant enzymes is a highly effective strategy for protection against carcinogenesis as well as slowing cancer development. Transcription factor Nrf2 (nuclear factor E2-related factor 2) is responsible for activation of phase II enzymes induced by natural chemopreventive compounds.
  
  
  METHODS
  Red ginseng oil (RGO) was extracted using a supercritical CO2extraction system and chemical profile of RGO was investigated by GC/MS. Effects of RGO on regulation of the Nrf2/antioxidant response element (ARE) pathway were determined by ARE-luciferase assay, western blotting, and confocal microscopy.
  
  
  RESULTS
  The predominant components of RGO were 9,12-octadecadienoic acid (31.48%), bicyclo[10.1.0]tridec-1-ene (22.54%), and 22,23-dihydrostigmasterol (16.90%). RGO treatment significantly increased nuclear translocation of Nrf2 as well as ARE reporter gene activity, leading to upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1. Phosphorylation of the upstream kinases such as apoptosis signal-regulating kinase (ASK)1, mitogen-activated protein kinase (MAPK) kinase (MKK)4/7, c-Jun N-terminal kinase (JNK), and p38 MAPK were enhanced by treatment with RGO. In addition, RGO-mediated Nrf2 expression and nuclear translocation was attenuated by JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190.
  
  
  CONCLUSIONS
  RGO could be used as a potential chemopreventive agent, possibly by induction of Nrf2/ARE-mediated phase II enzymes via ASK1-MKK4/7-JNK and p38 MAPK signaling pathways.
authors.affiliation: Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, Korea; Department of Chemical Biology, Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Bak
authors.affiliation: Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, Korea.
authors.forename: Van-Long
authors.initials: VL
authors.lastname: Truong
authors.affiliation: Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, Korea.
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, Korea.
authors.forename: Xuan Ngan Giang
authors.initials: XN
authors.lastname: Nguyen
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
authors.affiliation: Ginseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation, Daejeon, Korea.
authors.forename: Soon-Gi
authors.initials: SG
authors.lastname: Hong
authors.affiliation: Ginseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation, Daejeon, Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, Korea.
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Jeong
keywords: antioxidant response element; cytoprotection; nuclear factor E2-related factor 2; phase II enzyme; red ginseng oil