Coffee, broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo – Studies in electrophile response element transgenic mice

Scope: Cytoprotective gene products, e.g. phase II – and antioxidant enzymes, are important in cellular redox homeostasis. A common feature of these genes is binding sites for transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), named electrophile response elements (EpREs) within their promoters. Methods and results: To identify dietary bioactive compounds and foods with Nrf2/EpRE inducing properties in an intact organism, we utilized transgenic mice encoding luciferase under control of EpRE from the thioredoxin promoter. We found that 18 of 31 phytochemicals and 10 of 14 dietary plant extracts induced EpRE activity in liver HepG2 cells. Surprisingly, some dietary plant extracts showed profound inducing capability as compared to pure compounds indicating combinatorial effects of compounds found in whole foods. Furthermore, intraperitoneal injections of carnosol, curcumin and tert benzohydroquinine induced EpRE-dependent promoter activity in transgenic mice. In further experiments with curcumin, we found highly induced EpRE activity in intestine, liver, kidney and spleen. Finally, a combination extract made of coffee, thyme, broccoli, rosemary, turmeric and red onion fed orally, induced EpRE mediated luciferase in lung and adipose tissue. Conclusion: These results show that plant-based foods contain compounds that can be absorbed and induce the antioxidant defence in a living organism in an organ-specific manner.