In an innovative study from NC Research Campus partners at the NC A&T Center for Excellence in Post-Harvest Technologies (the Sang lab) and the NC Central Nutrition Research Program (the Leung lab), scientists discovered four novel, cytoprotective compounds derived from dry ginger that act as the “most potent Nrf2 activators” in a zebrafish embryo model.
The study exams an intricate relationship between a protein, Keap1, and a transcription factor, Nrf2, which controls the bodily response to oxidative and electrophilic stress from chronic diseases like kidney disease, asthma, neurodegenerative disease, and cancer.
Normally, Keap1 works to degrade Nrf2 so a healthy cell has relatively low levels of the transcription factor in the cell at a given time. However, when Nrf2 receives messages from the cell that surrounding organelles are under duress, activated Nrf2 “detaches from Keap1 and migrates to the nucleus.” In the nucleus, Nrf2 prompts transcription of genes that protect the cell and detoxify the surrounding environment by binding to any antioxidant response element sequences that it encounters.
The ginger derivatives identified in this study provide a significant resource for activating Nrf2 to help prevent chronic diseases caused by oxidative stress. In a previous study from the same researchers, they pinpointed a dry ginger component called -shogaol as a major activator of Nrf2 in colon epithelial cells and in mice. This discovery led to the hypothesis tested and confirmed in the current study.
The findings from NC A&T and NC Central, incorporating a “structure-activity relationship study,” identified the most powerful Nrf2-activating ginger derivatives that work by prompting alkylation of cysteine residues of the cysteine-rich protein Keap1. Alkylation of Keap1 cysteine residues is an important signal for Nrf2 to detach and begin protecting cells from the nucleus.
The relationship between Keap1 and Nrf2 is characteristic of mouse and human systems as well as the zebrafish model. The similarities between humans and zebrafish in this way give NCRC researchers confidence that continued studies of ginger-derived, cytoprotective compounds are likely to continue providing insight into reversing oxidative and electrophilic stress, thereby reducing the impact of chronic diseases.
By: Kara Marker, NCRC Marketing