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. 2016 Feb 29;25(1):319–327. doi: 10.1007/s10068-016-0045-3

6-shogaol attenuates H2O2-induced oxidative stress via upregulation of Nrf2-mediated γ-glutamylcysteine synthetase and heme oxygenase expression in HepG2 cells

Jin-Kyoung Kim 1, Hae-Dong Jang 1,
PMCID: PMC6049361  PMID: 30263273

Abstract

The signaling pathway by which 6-shogaol protects HepG2 cells against H2O2-induced oxidative stress was investigated. Cellular anti-oxidant activities, the GSH level, and anti-oxidant response element (ARE) promoter activity were analyzed. Activated protein kinases and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, and phase II detoxification and anti-oxidant enzymes were analyzed using western blotting. 6-Shogaol enhanced cellular anti-oxidant activities, the GSH level, and ARE promoter activities. Nrf2 accumulation in the nucleus, c-jun N-terminal kinase (JNK) activation, and γ-glutamylcysteine synthetase (GCS) and heme oxygenase-1 (HO-1) expressions were increased by 6-shogaol. Blockage of the JNK signaling pathway removed the elicitation effect of 6-shogaol on JNK activation, Nrf2 accumulation in nucleus, and GCS and HO-1 expression, but partially suppressed cellular anti-oxidant activities and ARE promoter activities. 6-shogaol exerts an indirect cellular anti-oxidant activity based on up-regulation of GCS and HO-1 via a JNK-mediated Nrf2 signaling pathway.

Keywords: 6-shogaol, oxidative stress, c-jun N-terminal kinase-mediated, γ-glutamylcysteine synthetase, heme oxygenase-1

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