Oxidative stress, inflammation, and toxins.
They are a part of life for human beings, and even eating itself can trigger high levels of oxidative stress. These factors are a major contributor to diseases, including cancer, asthma, arthritis, heart disease, smoking-related diseases, and diseases of the brain such as Parkinson’s and Alzheimer’s.
Our group studies activation of the Nrf2 transcription factor by small molecules from edible plants and other sources. Upon activation, Nrf2 increases the expression of proteins with detoxification, antioxidant, anti-inflammatory and damage repair functions, collectively called cytoprotective proteins. There is strong scientific evidence that regular and adequate consumption of foods that activate the body’s cytoprotective enzymes can lower oxidative stress, toxins and inflammation levels in the body, in turn preventing or mitigating various chronic diseases. A wide variety of foods contain compounds that activate Nrf2, for example EGCG from green tea, shogaols from ginger, and sulfur compounds from garlic and onions as well as cruciferous vegetables.
Our most recent work uncovered opposing effects of reactive oxygen species (ROS) on activation of the Nrf2 pathway by the clinically-investigated molecule sulforaphane. The ROS-generating molecule di-tert-butylhydroquinone (dtBHQ) widens the therapeutic window of sulforaphane, increasing its potency while having no effect on its toxicity at high concentrations. However, dtBHQ paradoxically also suppresses the levels of Nrf2, the transcription factor required for this activation. This work provides a model system for understanding the effects of small molecule co-treatment on this pathway, which ultimately could lead to better prevention of chronic diseases.