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Publication : Pau d'arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway.

First Author  Richter M Year  2014
Journal  J Toxicol Sci Volume  39
Issue  2 Pages  353-61
PubMed ID  24646717 Mgi Jnum  J:312152
Mgi Id  MGI:6783422 Doi  10.2131/jts.39.353
Citation  Richter M, et al. (2014) Pau d'arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway. J Toxicol Sci 39(2):353-361
abstractText  Pau d’arco is a plant-derived traditional medicine that acts by poorly understood molec-ular mechanisms. Here, we studied the effect of pau d’arco on the cytoprotective transcription factor Nrf2. An aqueous extract of pau d’arco stimulated Nrf2-dependent gene expression and led to nuclear localiza-tion of Nrf2 in vitro. Chromatographic separation and mass spectrometry of the extract identified ben-zene trioles or benzene tetraoles within the active fractions. The extract stimulated the mitogen-activat-ed protein kinase/extracellular-signal-regulated kinase kinase (MEK)/extracellular-signal-regulated kinase (ERK1/2) pathway. The pharmacological inhibition of MEK, but not of p38 mitogen-activated protein kinase, glycogen synthase kinase-3 or phosphoinositide 3-kinase was required for the activation of Nrf2-dependent gene expression by pau d’arco, but not for the nuclear translocation of Nrf2. In vivo pau d’arco increased the expression of Nrf2-target genes in the intestine. The results suggest that the activation of Nrf2 could mediate beneficial effects of pau d’arco, in particular in the intestine.
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