title: Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin.
abstract: Numerous studies have reported a potent induction of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent gene expression by the isothiocyanate sulforaphane. However, little is known regarding the Nrf2-inducing activities of the lower structure-related sulforaphane homologues, such as iberverin, iberin and cheirolin, which exhibit different sulfur oxidation states. Therefore, in this study we synthesized the isothiocyanates iberverin, iberin and cheirolin with a high yield and purity and determined their Nrf2-inducing activity in NIH3T3 fibroblasts. Iberverin, iberin and cheirolin significantly induced Nrf2 nuclear translocation. The increase in nuclear Nrf2 levels was accompanied by a significant increase in heme oxygenase 1 (HO-1) and γ-glutamylcysteine synthetase (γGCS) mRNA and protein levels. Overall, iberverin, iberin and cheirolin exhibited a similar potency to sulforaphane in inducing Nrf2-dependent gene-expression. Furthermore, our data suggest that the induction of Nrf2 by iberverin, iberin and cheirolin may have occurred via an extracellular signal-related kinase (ERK)-dependent signal-transduction pathway.
authors: Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
authors: Insa M A
authors: IM
authors: Ernst
authors: Kalpana
authors: K
authors: Palani
authors: Tuba
authors: T
authors: Esatbeyoglu
authors: Karin
authors: K
authors: Schwarz
authors: Gerald
authors: G
authors: Rimbach
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D017879:Isothiocyanates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013440:Sulfides; D013450:Sulfones; C082585:iberin; C583310:cheirolin; C583309:iberverin