The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation.
Oxidative stress due to the presence
of excess reactive oxygen
species may cause cancers, aging, and many other conditions. Nuclear
factor erythroid 2-related factor 2 (Nrf2) may control abnormal oxidative
stress as a transcription factor by inducing antioxidant-related genes
via antioxidant response elements (AREs) in the gene promoters. The
11 triterpenoid saponins (1–11) isolated
from Camellia japonica roots were tested for ARE-luciferase
activity and Nrf2 accumulation in human keratinocytes (HaCaT cells).
The ARE-luciferase activity was significantly increased by compounds 1–11 (25 μM) as a result of nuclear
Nrf2 accumulation in the cells. Thus, these compounds may contribute
to the induction of Nrf2 activity against oxidative damage in cells.
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