“Reports on the benefits of red wine are almost two centuries old,” said Lindsay Brown, associate professor in the School of Biomedical Sciences at The University of Queensland and corresponding author for the study. “The media developed the more recent story of the French paradox in the early 1990s. However, studies on the actions of resveratrol, one of the active non-alcoholic ingredients, were uncommon until research around 1997 showed prevention of cancers. This led to a dramatic interest in this compound.”

Red wine contains a complex mixture of bioactive compounds, including flavonols, monomeric and polymeric flavan-3-ols, highly colored anthocyanins, as well as phenolic acids and the stilbene polyphenol, resveratrol. Brown said that some of these compounds, particularly resveratrol, appear to have health benefits.

“The breadth of benefits is remarkable – cancer prevention, protection of the heart and brain from damage, reducing age-related diseases such as inflammation, reversing diabetes and obesity, and many more,” said Brown. “It has long been a question as to how such a simple compound could have these effects but now the puzzle is becoming clearer with the discovery of the pathways, especially the sirtuins, a family of enzymes that regulate the production of cellular components by the nucleus. ‘Is resveratrol the only compound with these properties?’ This would seem unlikely, with similar effects reported for other components of wine and for other natural products such as curcumin. However, we know much more about resveratrol relative to these other compounds.”

Stephen Taylor, professor of pharmacology at the University of Queensland, agreed that resveratrol is the “compound du jour.”

“I think that red wine has both some mystique and some historical symbolism in the west,” said Taylor, “and of course, some various pleasures attached to its ingestion, all of which give it a psychological advantage edge, food-wise. Not many of us can or will eat a couple of cups of blueberries a day for years on end, but if we could do a population study for a decade or so on such a group, you might actually see similar results.”

Key points of the review include:

  • Resveratrol exhibits therapeutic potential for cancer chemoprevention as well as cardioprotection.

“It sounds contradictory that a single compound can benefit the heart by preventing damage to cells, yet prevent cancer by causing cell death, said Brown. “The most likely explanation for this, still to be rigorously proved in many organs, is that low concentrations activate survival mechanisms of cells while high concentrations turn on the in-built death signals in these cells.”

  • Resveratrol may aid in the prevention of age-related disorders, such as neurodegenerative diseases, inflammation, diabetes, and cardiovascular disease.

“The simplest explanation is that resveratrol turns on the cell’s own survival pathways, preventing damage to individual cells,” said Brown. “Further mechanisms help, including removing very reactive oxidants in the body and improving blood supply to cells.”

  • Low doses of resveratrol improve cell survival as a mechanism of cardio- and neuro-protection, while high doses increase cell death.

“The key difference is probably the result of activation of the sirtuins in the nucleus,” said Brown. “Low activation reverses age-associated changes, while high activation increases the process of apoptosis or programmed cell death to remove cellular debris. Similar changes are seen with low-dose versus high-dose resveratrol: low-dose resveratrol produces cellular protection and reduces damage, while high-dose resveratrol prevents cancers.”

In summary, noted Brown, current scientific research is starting to explain reports from the last 200 years that drinking red wine improves health. “It is a cliché that ‘nature is a treasure trove of compounds,’ but studies with resveratrol show that this is correct! We need to understand better the vast array of compounds that exist in nature, and determine their potential benefits to health.”

“There is one particular point that deserves fleshing out,” added Taylor. “Resveratrol is largely inactivated by the gut or liver before it reaches the blood stream, where it exerts its effects – whatever they may be – good, bad, or indifferent. Thus, most of the reseveratrol in imbibed red wine does not reach the circulation. Interestingly, absorption via the mucous membanes in the mouth can result in up to around 100 times the blood levels, if done slowly rather than simply gulping it down. Of course, we don’t know if these things matter yet, but issues like this are real and generally ignored by all.”

http://www.uq.edu.au

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A study published in the November 11 issue of the Journal of Biological Chemistry shows that resveratrol, a compound found in grapes and red wine, lowers the levels of the amyloid-beta peptides which cause the telltale senile plaques of Alzheimer’s disease.

“Resveratrol is a natural polyphenol occurring in abundance in several plants, including grapes, berries and peanuts,” explains study author Philippe Marambaud. “The polyphenol is found in high concentrations in red wines. The highest concentration of resveratrol has been reported in wines prepared from Pinot Noir grapes. Generally, white wines contain 1% to 5% of the resveratrol content present in most red wines.”

One of the characteristic features of Alzheimer’s disease is the deposition of amyloid-beta peptides in the brain. Philippe Marambaud and his colleagues at the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease and Memory Disorders in Manhasset, New York, administered resveratrol to cells which produce human amyloid-beta and tested the compound’s effectiveness by monitoring amyloid-beta levels inside and outside the cells. They found that levels of amyloid-beta in the treated cells were much lower than those in untreated cells.

The researchers believe the compound acts by stimulating the degradation of amyloid-beta peptides by the proteasome, a barrel-shaped multi-protein complex that can specifically digest proteins into short polypeptides and amino acids.

However, eating grapes may not be a cure for Alzheimer’s disease. “It is difficult to know whether the anti-amyloidogenic effect of resveratrol observed in cell culture systems can support the beneficial effect of specific diets such as eating grapes,” cautions Marambaud. “Resveratrol in grapes may never reach the concentrations required to obtain the effect observed in our studies. Grapes and wine however contain more than 600 different components, including well-characterized antioxidant molecules. Therefore, we cannot exclude the possibility that several compounds work in synergy with small amounts of resveratrol to slow down the progression of the neurodegenerative process in humans.”

Following up on their studies, Marambaud and his colleagues are trying to figure out how resveratrol exerts its effects in order to develop similar compounds to use in fighting Alzheimer’s disease. “Our long-term goal is now to elucidate the exact molecular mechanisms involved in the beneficial properties of resveratrol as a necessary prerequisite to the identification of novel molecular targets and therapeutic approaches,” says Marambaud. “The observation that resveratrol has a strong anti-amyloidogenic activity is a powerful starting point for screening analogues of resveratrol for more active and more stable compounds, a task in which our laboratory is actively involved. We have already obtained analogues of resveratrol that are 20 times more potent than the original natural compound. We are now aiming to find more stable analogues and to test them in vivo in mice.”

Additional good news is that resveratrol may also be effective in fighting other human amyloid-related diseases such as Huntington’s, Parkinson’s and prion diseases. Studies by a group at the Institut National de la Santé et de la Recherche Médicale in Paris, France headed by Christian Néri have recently shown that resveratrol may protect neurons against amyloid-like polyglutamines, a hallmark of Huntington’s disease.

http://www.asbmb.org/

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