Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1–MKK4/7–JNK and p38 MAPK signaling pathways in HepG2 cells

Autor: Min Ji Bak, Van-Long Truong, Se-Yeon Ko, Xuan Ngan Giang Nguyen, Mira Jun, Soon-Gi Hong, Jong-Won Lee, Woo-Sik Jeong
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Journal of Ginseng Research, Vol 40, Iss 4, Pp 423-430 (2016)
Druh dokumentu: article
ISSN: 1226-8453
DOI: 10.1016/j.jgr.2016.07.003
Popis: 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.
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