The identification of oxidant-sensitive pathways of cell signaling mandated that antioxidants regulate gene expression. Basically, three different mechanisms exist: First, by affecting the cell’s redox status; this is largely controlled by
the balance between oxidants, free radicals, and the antioxidant network. Second, there is the activation of phase 2 enzymes, which strengthen antioxidant defense, and are also active in detoxification and chemoprevention. Then, there are the specific effects of antioxidants on key targets of the transciptome. In the 1990s, we turned our attention toward antioxidant regulation of oxidant-sensitive transcription factors, such as NfkB and dependent genes as cell adhesion molecule and iNOS gene expression. Our findings identified specific cell targets of gene regulation by bioflavonoid-rich botanical extracts as Ginkgo biloba EGb 761. Interestingly, this extract exhibits greater activity than any of their individual bioflavonoid components, thus, suggesting synergistic effects by their complex mixture of components. Global gene expression analysis with high-density oligonucleotide arrays is being used for studies of gene regulation and some recent findings will be reported for Ginkgo biloba extract EGb 761 which has been investigated in cell culture and animal model systems. In cell culture systems, oxidative stress linked affects on genes expression can readily be demonstrated. In vivo results reveal the presence of neuromodulatory substances in EGb 761.