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

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.