[Rhonda]: And one of those, I guess, one of the main protective mechanisms would be the
Nrf2 pathway.
[Jed]: Yeah.
So I have a feeling that sulforaphane would be just be another interesting phytochemical
if at almost the same time, we, and I use the term "we" loosely because I was only very
peripherally involved with this.
But a number of people at Johns Hopkins and in Japan discovered, in Japan and England,
I should say, but a small number of people discovered this Nrf2 pathway and really fleshed
out all the details of it.
And this happened in parallel to the interest in sulforaphane and broccoli.
And it turns out that the Nrf2 pathway is an extremely important pathway for up-regulating
the protective enzymes and protective proteins including perhaps the heat shock proteins
in cells so that they can protect themselves against various insults.
It's an integral part of protection against a variety of chronic diseases.
And as I say, Tom Kensler and Paul Talalay, Albena Dinkova-Kostova all at Hopkins, Masi
Yamamoto in Japan, John Hayes in England, excuse me, and I'm certainly leaving out a
few people, but small number of people initially put this pathway on the map.
And it turns out that the Nrf2 pathway controls something between 3% and 5% of our cellular
proteins.
So it's very important.
[Rhonda]: Wow.
I didn't realize it's that much.
[Jed]: Yeah.
And why is it important?
It's important because it recognizes molecules like sulforaphane through a system, a bio-chemical
system that I hesitate to explain without props and graphs, and also because I'm not
the world's expert on this, certainly.
But it recognizes sulforaphane or other similar molecules as they enter cells in the cytoplasm
of the cells.
Then there's actually a chaperone protein that's in the cytoplasm.
It's called Keap1.
That molecule when it binds to sulforaphane, or vice versa, changes in conformation and
it releases Nrf2, which then migrates to the nucleus and turns on or up-regulates the antioxidant
response element which is responsible for the transcription, for initiating transcription
of a whole series of protective genes or genes in coding for a bunch of protective enzymes.
And this happens very quickly, this protective response, and its quite efficient.
So to get back to sulforaphane, so sulforaphane was discovered and then everybody started
searching for the mechanism by which it acted.
The Keap1-Nrf2 mechanism was discovered, and they sort of both developed a following, if
you will, in parallel.
And it turns out that sulforaphane is still probably the most potent activator of Nrf2
to be found naturally in from the natural world.
There have been synthetic activators that are more potent, that have been produced,
been made chemically, but sulforaphane still sort of takes the cake in terms of its protective
ability, and ability to up-regulate protective enzymes.