Nrf2 (Nuclear factor erythroid 2-related factor 2) is a transcription factor that I talk about often that plays a crucial role in regulating the expression of genes involved in the cellular response to oxidative stress, inflammation, and detox. And the reason I talk about Nrf2 so much is that the Stabilized Sulforaphane in BrocElite® Plus is the best natural molecule at turning on Nrf2.
Tight junctions (TJs) are specialized structures that form a barrier between adjacent cells and are critical for maintaining the integrity of various tissues, including the epithelial and endothelial layers. While I often talk about TJs in the gut barrier, they are located in many places in the body, including the blood-brain barrier. Studies have shown that Nrf2 regulates TJs by modulating the expression of various TJ-associated proteins.
TJ-associated proteins, such as claudins, occludin, and ZO-1, are integral membrane proteins that are essential for the formation and maintenance of TJs. These proteins are responsible for regulating the permeability of the barrier and preventing the diffusion of substances between adjacent cells. Studies have shown that Nrf2 can regulate the expression of these proteins by binding to specific DNA sequences in the promoter regions of their respective genes.
Activation of Nrf2 leads to an increase in the expression of TJ-associated proteins, which enhances the barrier function of TJs. In fact, Dr. John Gildea, who stabilized sulforaphane in BrocElite®, says that Nrf2 is the master regulator of TJs.
“Nrf2 is the master regulator of Tight Junctions.”
-Dr. John Gildea
For example, in a study of mice with colitis, Nrf2 activation was shown to increase the expression of claudin-1 and occludin in the intestinal epithelium, which improved barrier function and protected against intestinal inflammation (1). Similarly, in a study of rats with acute lung injury, Nrf2 activation was shown to increase the expression of ZO-1 and occludin in lung epithelial cells, which improved barrier function and protected against lung injury (2).
In contrast, inhibition of Nrf2 activity leads to a decrease in the expression of TJ-associated proteins, resulting in a compromised barrier function. For example, in a study of mice with sepsis, inhibition of Nrf2 activity was shown to decrease the expression of claudin-5 and occludin in brain endothelial cells, leading to blood-brain barrier (BBB) dysfunction and increased brain edema (3). Similarly, in a study of rats with liver injury, inhibition of Nrf2 activity was shown to decrease the expression of occludin and ZO-1 in liver cells, leading to liver damage and dysfunction (4).
Our internal research shows that the amount of glyphosate in a fast-food meal can decrease Nrf2 by 30%. Here is a list of common foods to avoid if you’re concerned about glyphosate. We also show that taking BrocElite® after glyphosate exposure can return Nrf2 function to normal.
And when Nrf2 is low and TJs aren’t functioning properly, the result in the gut is what’s called “leaky gut” or intestinal permeability and in the brain you have “leaky brain.”
Overall, these studies suggest that Nrf2 plays a critical role in regulating the expression of TJ-associated proteins and, in turn, the barrier function of TJs in various tissues. Nrf2 activation can lead to an increase in the expression of these proteins, which enhances the barrier function and protects against tissue damage and inflammation, while inhibition of Nrf2 activity can lead to a decrease in their expression, compromising the barrier function and contributing to tissue damage and inflammation.
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- Li Y, Li J, Li S, Li Y, Wang X, Liu B, He X, Ding X. Nrf2 mediates the protective effect of 2-oxoglutarate on intestinal barrier function. J Nutr Biochem. 2018 Apr;54:24-32. doi: 10.1016/j.jnutbio.2017.10.010.
- Cho HY, Reddy SP, Debiase A, Yamamoto M, Kleeberger SR. Gene expression profiling of Nrf2-mediated protection against oxidative injury. Free Radic Biol Med. 2005 Dec 1;39(11):1401-12. doi: 10.1016/j.freeradbiomed.2005.06.004.
- Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med. 2008 Oct 15;44(8):723-38. doi: 10.1016/j.freeradbiomed.2007.11.005
- Shah ZA, Li RC, Thimmulappa RK, Kensler TW, Yamamoto M, Biswal S, Doré S. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience. 2007 Apr 25;147(1):53-9. doi: 10.1016/j.neuroscience.2007.02.066.