title: Pau d'arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway.
abstract: Pau d'arco is a plant-derived traditional medicine that acts by poorly understood molecular 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 localization of Nrf2 in vitro. Chromatographic separation and mass spectrometry of the extract identified benzene trioles or benzene tetraoles within the active fractions. The extract stimulated the mitogen-activated 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.
authors.affiliation: Sanofi-Aventis Deutschland, R&D, Industriepark Hoechst, Germany.
authors.forename: Michelle
authors.initials: M
authors.lastname: Richter
authors.forename: Angelika F
authors.initials: AF
authors.lastname: Winkel
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schummer
authors.forename: Martin
authors.initials: M
authors.lastname: Gerlitz
authors.forename: Meltsje
authors.initials: M
authors.lastname: de Hoop
authors.forename: Bodo
authors.initials: B
authors.lastname: Brunner
authors.forename: Maike
authors.initials: M
authors.lastname: Glien
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmoll
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007422:Intestines; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D000072019:Kelch-Like ECH-Associated Protein 1; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008519:Medicine, Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D013268:Stimulation, Chemical; D029663:Tabebuia; D014867:Water
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D014867:Water; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human