Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells
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 act...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Journal of Ginseng Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S122684531630077X |
| _version_ | 1811262080706150400 |
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| author | Min Ji Bak Van-Long Truong Se-Yeon Ko Xuan Ngan Giang Nguyen Mira Jun Soon-Gi Hong Jong-Won Lee Woo-Sik Jeong |
| author_facet | Min Ji Bak Van-Long Truong Se-Yeon Ko Xuan Ngan Giang Nguyen Mira Jun Soon-Gi Hong Jong-Won Lee Woo-Sik Jeong |
| author_sort | Min Ji Bak |
| collection | DOAJ |
| description | 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 CO2 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. |
| first_indexed | 2024-04-12T19:17:39Z |
| format | Article |
| id | doaj.art-f1f4afc416a8496983c34e1e36f54584 |
| institution | Directory Open Access Journal |
| issn | 1226-8453 |
| language | English |
| last_indexed | 2024-04-12T19:17:39Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ginseng Research |
| spelling | doaj.art-f1f4afc416a8496983c34e1e36f545842022-12-22T03:19:41ZengElsevierJournal of Ginseng Research1226-84532016-10-0140442343010.1016/j.jgr.2016.07.003Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cellsMin Ji Bak0Van-Long Truong1Se-Yeon Ko2Xuan Ngan Giang Nguyen3Mira Jun4Soon-Gi Hong5Jong-Won Lee6Woo-Sik Jeong7Department of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, KoreaDepartment of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, KoreaDepartment of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, KoreaDepartment of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan, KoreaGinseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation, Daejeon, KoreaGinseng Product Research Institute, R&D Headquarters, Korea Ginseng Corporation, Daejeon, KoreaDepartment of Food and Life Sciences, College of Biomedical Science and Engineering, Inje University, Gimhae, KoreaBackground: 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 CO2 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.http://www.sciencedirect.com/science/article/pii/S122684531630077Xantioxidant response elementcytoprotectionnuclear factor E2-related factor 2phase II enzymered ginseng oil |
| spellingShingle | Min Ji Bak Van-Long Truong Se-Yeon Ko Xuan Ngan Giang Nguyen Mira Jun Soon-Gi Hong Jong-Won Lee Woo-Sik Jeong Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells Journal of Ginseng Research antioxidant response element cytoprotection nuclear factor E2-related factor 2 phase II enzyme red ginseng oil |
| 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 |
| title_full | Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells |
| title_fullStr | Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells |
| title_full_unstemmed | Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells |
| title_short | Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells |
| title_sort | induction of nrf2 are mediated cytoprotective genes by red ginseng oil through ask1 mkk4 7 jnk and p38 mapk signaling pathways in hepg2 cells |
| topic | antioxidant response element cytoprotection nuclear factor E2-related factor 2 phase II enzyme red ginseng oil |
| url | http://www.sciencedirect.com/science/article/pii/S122684531630077X |
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