Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin

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 iberve...

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Bibliographic Details
Published in:Pharmacological research 2013-04, Vol.70 (1), p.155-162
Main Authors: Ernst, Insa M.A., Palani, Kalpana, Esatbeyoglu, Tuba, Schwarz, Karin, Rimbach, Gerald
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Animals
Blotting, Western
Cell Culture Techniques
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cell Survival - drug effects
Cheirolin
Chemical isothiocyanate synthesis
Chromatography, High Pressure Liquid
Iberin
Iberverin
Isothiocyanates - chemical synthesis
Isothiocyanates - chemistry
Isothiocyanates - pharmacology
Mice
Molecular Structure
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
NIH 3T3 Cells
Nrf2
Real-Time Polymerase Chain Reaction
Signal Transduction - drug effects
Structure-Activity Relationship
Sulfides - chemical synthesis
Sulfides - chemistry
Sulfides - pharmacology
Sulfones - chemical synthesis
Sulfones - chemistry
Sulfones - pharmacology
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Summary: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.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2013.01.011