Resveratrol
Poltronieri Palmiro
Monday, 14 July 2008 12:49 UTC
The French paradox in the wine drinking life-style consists in longer “life expectances” in people drinking wine, french, italian, or spanish individuals. This is even more apparent with red wines. The red intensity in wines derives from a prolonged fermentation in presence of grape envelops, that release anthocianins and flavonoids. Resveratrol is the major flavonoid and antioxidant in red wines. Recently, in the review by Kundu and Suhr, Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives, Cancer Letters 2008, are described the principal enzyme targets and intracellular pathways affected by resvetratrol. On a large industrial scale, the molecule structure has been redesigned and new, synthetic resveratrol mimetics are produced to be applied for pharmaceutical and therapeutical use.
How will be our life in a world of synthetic bioactives? will be we able to cope to a similar extent the continuing fight and counterbalance between pro-oxidants and anti-oxidants, as well as with natural bioactives?
One interesting finding of the colleague Peter Winter, is that the apparatus engaged between ROS and the counter-effecting pro-oxidants is already present in the cells, and requires the elimination of a negative feedback in order to become operative.
So one of the differences between strongly responsive people, resisting to reactive oxigen species, and less strongly responsive one, is in the response itself. As in plants, most susceptible varieties react in the wrong way, and this may be detected already before the response is triggered.
As a consequence to this supposition, the bioactives will have additive effect only in the first case, whereas they will just try to limit the damages in the second group of individuals.
are you of the same opinion?
do you think there are other factors limiting or adding more complexity to this simplified scheme?
looking forward to discussing your comments.
Updated 14 July 2008 15:03 UTC
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Replies
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Very interesting topic. Will highly active mimetics of naturally occurring compounds be good for us, or just throw out of whack the body’s system of checks and balances (feedback and regulatory loops). Seems like in this case, it’s easy to have too much of a good thing.
Do we know what happens when the system is flooded with anti-oxidants (the non-water soluble and non-easily eliminated kind) or oxidant inhibitors? What about resveratrol? Is the mimetic is much more potent than the stuff isolated from wine? I read somewhere that one would have to drink something like 75 bottles of wine a day to get the same levels of resveratrol that were necessary to extend life in lab rats. I like wine quite a bit, but that is too much even for me. What is the long term effect of high doses of resveratrol? What is the effect of modulating the SIRT1 pathway, affected by resveratrol? Is it known?
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Thanks to the comment posted, I will add few points to put this topic in a science-oriented perspective.
The bioavailability of compounds, from their introduction with food, to the assimilation and distribution within the body, depends on their solubility, and compounds as resveratrol are soluble in alcohol. This is one of the reasons why research and companies focused on its derivatives, as esthers.
Now, the agreement between GlaxoSmithKline, that acquired Sirtis (Cambridge, Boston hub) and this company, tends to put forward the clinical trials, for application of resveratrol in support therapy of diabetes, cardiovascular diseases, as well as in cancer. Sirtis signed, before that, an agreement with NIH for the exchange of proprietary IPR and patents for this same aim. Before this, another joint agreement was done between Xenomics and Harvard Medical School. I think that a concentration of so great industrial attention on these compounds means a lot on the importance they give to them, and also that companies intend to put forward the heavily costly trials that are essential before their application in therapies.
I did not mean to expect any extension of life, but it would be great to alleviate or improve the quality of life of individuals suffering of chronic diseases. BTW, it will mean also a great income for pharma companies after the launch on the market of the approved products. -
Reveratrol helps slow aging by molecular interaction with our cells. When Resveratrol molecules enter our cells it stimulates the production of an enzyme called SIRT1 which in turn, spawns more mitochondria in muscle and other tissues.
resveratrol reviews -
Hi Palmiro, Nice topic to discuss about, and I am posting a few comments on resveratrol in addition to your comments.According to Dr.Oz,Resveratrol is found in its highest concentration in the Japanese root, Knotweed and the Muscadine grape skin, if consumed over prolonged periods of time has now been medically proven to naturally cleanse and scrub your arteries.
In Okinawa, Knotweed is consumed in their staple diet and has also been used for centuries to treat a number of ailments.
These include the treatment of allergic and inflammatory disorders as well as offering lipid therosclerosis medication and liver ailments to assist in the recovery of Hepatitis B.
In fact, the people of Okinawa have some of the lowest rates of cancer sufferers in the world, and the fact that you stand and 86% chance of more likely developing cancer in the U.S than you do if you were born and raised in Okinawa is a startling and baffling statistic.
Scientists are still trying to unravel the effects “pure resveratrol” has on our immune system, but it is clear their is more to resveratrol than has so far been medically proven – through the eyes of western science.
Whether it’s fast food, power foods or freezer food you consume, all these diets will continually abuse your arteries each day by lining your arteries with manufactured toxins so having the ability to naturally scrub your arteries each day without exercise is a first.
Resveratrol also restores endothelial function in type 2 diabetes by inhibiting TNF -induced activation of NADH oxidase and preserving eNOS phosphorylation, suggesting the potential for new treatment approaches to promote vascular health in metabolic diseases. -
thanks for your recent posts that help to deepen this discussion. There is a lot to do at the lab level in this field, I’d like to move to Okinawa and try their
dancemusicdiet for a change, so to extend my life expectation.
Recently we heard a seminar by Eugenio Butelli, a post-doc in the Cathie Martin group at John Innes Centre, where they are producing plants with altered regulatory steps in the biosynthetic pathway of polyphenols, thus producing fruits with anthocyanins, or other polyphenols (purple tomato). The extracts may be tested in animal studies as well as in cell cultures.
One important effect of resveratrol is the binding to SIRTuins. In older papers it was described an increase in SIRT1 histone deacetylase activity. However, it was shown that the beneficial effect is maintained even in the presence of a mutant SIRT1, devoid of deacetylase activity. So another explanation could be its relocalisation within the cell compartments.
In addtion to study the plant extracts on cell cultures, one tends to generalise on their effects in the cells, but it is important to evaluate the bioavailability of the individual bioactive. For this purpose, it may be interesting to test the extract in vitro and measure its effect on the enzymatic activity of a protein target. In case of histone deacetylase activity is measured to be increased, we can conclude that this compound was producing the effect seen in the cells.
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