Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4/7-JNK and p38 MAPK signaling pathways in HepG2 cells

  • Bak, Min Ji (Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University) ;
  • Truong, Van-Long (Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University) ;
  • Ko, Se-Yeon (Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University) ;
  • Nguyen, Xuan Ngan Giang (Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University) ;
  • Jun, Mira (Department of Food Science and Nutrition, Dong-A University) ;
  • Hong, Soon-Gi (Ginseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation) ;
  • Lee, Jong-Won (Ginseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation) ;
  • Jeong, Woo-Sik (Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University)
  • Received : 2016.05.17
  • Accepted : 2016.07.09
  • Published : 2016.10.15
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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 $CO_2$ extraction 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. Conclusion: 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.

Keywords

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