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[10]-Gingerol from Zingiber Officinale Reduces Oxidative Stress via the ERK/Nrf2/HO-1 Signaling Pathway in Human Keratinocytes

The present study was designed to investigate the molecular mechanisms of bioactive components against mild oxidative stress in human keratinocytes (HaCaTs). Solvent extraction and fractionation of the rhizomes of Zingiber officinale resulted in the isolation of [10]-gingerol. At concentrations of 1, 3, and 5 µM [10]-gingerol dose-dependently increased HO-1 (heme oxygenase-1) mRNA and protein levels, with a significant effect at 5 µM. This augmentation of HO-1 by [10]-gingerol was attributed to the upregulation of Nrf2 (nuclear factor erythroid 2-related factor 2), which markedly reduced the cytoplasmic stability of Keap1 (kelch-like ECH-associated protein 1). Furthermore, our findings indicate that the upregulation of HO-1 by [10]-gingerol increased resistance to mild oxidative stress, suggesting that [10]-gingerol might enhance the activities of antioxidant enzymes by stimulating Nrf2. Our experimental findings indicate that the mild attenuating effect of [10]-gingerol against oxidative stress involves the ERK/Nrf2/HO-1 signaling pathway.