Resveratol is volgens wetenschappers een sterke anti-oxidant.  O.a. in rode wijn en rode vruchten als bessen enz. komt deze stof veel voor en daarom wordt aangeraden regelmatig een glaasje rode wijn te drinken. Zie samenstelling en vergelijk met andere dranken van glas rode wijn op pagina uitgangspunten Houtsmullerdieet (drinken). Klik hier voor informatie op Wikipedia over resveratrol.

 Ik mis de kennis en de tijd om onderstaand artikel over resveratol goed te vertalen, maar voor wie goed Engels leest hier wordt uitgelegd wat resveratol is en hoe het werkt. Met onderaan een aantal studies vermeld. Ook een studieresultaat zoals Nature dat meldde.

Resveratrol (trans-3,5,4'-trihydroxystilbene), a compound found largely in the skins of red grapes, is a component of Ko-jo-kon, an oriental medicine used to treat diseases of the blood vessels, heart, and liver. It came to scientific attention only a few years ago, however, as a possible explanation for the "French Paradox" -- the low incidence of heart disease among the French people, who eat a relatively high-fat diet. Today, it is touted by manufacturers and being examined by scientific researchers as an antioxidant, an anti-cancer agent, and a phytoestrogen. It is also being advertised on the Internet as "The French Paradox in a bottle." This article reviews the recent research on resveratrol's physiologic activity.

Resveratrol is the parent compound of a family of molecules, including glucosides and polymers, existing in cis and trans configurations in a narrow range of spermatophytes of which vines, peanuts and pines are the prime representatives. Its synthesis from p-coumaroyl CoA and malonyl CoA is induced by stress, injury, infection or UV-irradiation, and it is classified as a phytoalexin anti-fungicide conferring disease resistance in the plant kingdom. In vitro, ex vivo and animal experiments have shown that it possesses many biological attributes that favour protection against atherosclerosis, including antioxidant activity, modulation of hepatic apolipoprotein and lipid synthesis, inhibition of platelet aggregation as well as the production of pro-atherogenic eicosanoids by human platelets and neutrophils. Red wine represents its main source in the human diet, and it has been proposed as a major constituent of the polyphenol fraction to which the health benefits of red wine consumption have been attributed. Th e past several years have witnessed intense research devoted to its measurement in wine and the factors likely to promote its enrichment in this beverage. Up to the present, conclusive evidence for its absorption by human subjects in biologically significant amounts is lacking, and it is questionable (but not yet excluded) that its powerful and beneficial in vitro activities are reproduced as a consequence of sustained moderate red wine consumption.

Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

While present in other plants, such as eucalyptus, spruce, and lily, and in other foods such as mulberries and peanuts, resveratrol's most abundant natural sources are Vitis vinifera, labrusca, and muscadine grapes, which are used to make wines. It occurs in the vines, roots, seeds, and stalks, but its highest concentration is in the skin, which contains 50-100 micrograms (µg) per gram. Resveratrol is a phytoalexin, a class of antibiotic compounds produced as a part of a plant's defense system against disease. For example, in response to an invading fungus, resveratrol is synthesized from p-coumaroyl CoA and malonyl CoA. Since fungal infections are more common in cooler climates, grapes grown in cooler climates have a higher concentration.

The resveratrol content of wine is related to the length of time the grape skins are present during the fermentation process. Thus the concentration is significantly higher in red wine than in white wine, because the skins are removed earlier during white-wine production, lessening the amount that is extracted. Grape juice, which is not a fermented beverage, is not a significant source of resveratrol. A fluid ounce of red wine averages 160 µg of resveratrol, compared to peanuts, which average 73 µg per ounce. Since wine is the most notable dietary source, it is the object of much speculation and research.

Resveratrol is a compound produced by many plant species and is thought to be helpful in reducing serum lipids and may have favorable cardiovascular implications. It is produced by Vitis vinifera and labrusca grapes and is found in grape products including red and white wines. There is a lack of information about resveratrol in muscadine (V. rotundifolia), so two studies were made to check bronze- and dark-skinned muscadines (and products made from them) for resveratrol. The first study established that resveratrol is a natural constituent of muscadine berries, berries without seed and seeds alone. The second study measured resveratrol in such muscadine products as wine, unfiltered juice, pomace and in purees made from pomace. Significant amounts of resveratrol were found in pomace. Muscadines wines compared favorably in resveratrol concentration with wines reported in the literature. The consumption of muscadines and muscadine products, especially those made from pomace purees, could help incorporate a sign ificant quantity of resveratrol into the average diet.

Many studies suggest that consuming alcohol (especially red wine) may reduce the incidence of coronary heart disease (CHD). Several studies have demonstrated that resveratrol is an effective antioxidant. It inhibits lipid peroxidation of low-density lipoprotein (LDL), prevents the cytotoxicity of oxidized LDL, and protects cells against lipid peroxidation. It is thought that because it contains highly hydrophilic and lipophilic properties, it can provide more effective protection than other well-known antioxidants, such as vitamins C and E. On the other hand, it is less effective than the antioxidants quercetin and epicatechin found in red wine. Reduced platelet aggregation has also been demonstrated in studies on resveratrol, further contributing to its prevention of atherosclerosis. To date, most of the research on resveratrol's antioxidant and anti-platelet properties has been done in vitro (in an artificial environment using test-tube or tissue-culture preparations). Further studies in animals and humans are necessary to determine whether resveratrol supplementation makes sense.

Resveratrol is being studied to see how it affects the initiation, promotion, and progression of cancer. With regard to tumor initiation, it has been shown to act as an antioxidant by inhibiting free radical formation, and as an anti-mutagen in rat models. Resveratrol appears to decrease tumor promotion activity by inhibiting cyclooxygenase-1 (COX-1), an enzyme that converts arachidonic acid to pro-inflammatory substances that stimulate tumor-cell growth. Studies related to progression have found that resveratrol induced human promyelocytic leukemia cell differentiation and inhibited ribonucleotide reductase, an enzyme needed for DNA synthesis in proliferating cells. One appealing characteristic of resveratrol's anti-cancer potential is its minimal toxicity to blood-forming cells. More studies using both cellular and animal models are needed before any such data would be applicable to human use.

The similarity in structure between resveratrol and diethylstilbestrol (a synthetic estrogen) has prompted investigations into resveratrol's potential as a phytoestrogen (a plant compound that produces estrogen-like effects). However, these properties also stimulate the growth of human breast cancer cells. This finding seems contrary to its other anticancer activities, and is a cause for concern. 

A group of Functional Foods for Health (FFH) Program scientists led by Dr. John Pezzuto in the College of Pharmacy at the UIC campus have recently shown that a substance in grapes may prevent cancer.

In the study, Pezzuto and colleagues were able to show that resveratrol was effective during all three phases of the cancer process: initiation, promotion and progression. Resveratrol was found to have antioxidant and antimutagenic activity and also increased levels of the phase II drug-metabolizing enzyme quinone reductase, an enzyme capable of metabolically detoxifying carcinogens, thereby ridding them from the body. All three of these physiological effects are indicative of resveratrol preventing cancer initiation--the initial, irreversible stage of the cancer process. Resveratrol also demonstrated antiinflammatory effects and inhibited the activity of the cyclooxygenase and hydroperoxidase enzymes (suggestive of antipromotion activity) in addition to causing the differentiation of human promyelocytic leukemia cells, indicating that this compound may also depress the progression phase of cancer. Finally, resveratrol inhibited the development of preneoplastic lesions in mouse mammary glands treated with a carcinogen in culture and inhibited tumor formation in mice. No toxic effects were observed.

The UIC researchers originally isolated resveratrol from a crude extract of the roots of a tree collected in Peru under a grant from the National Cancer Institute which involves screening for cancer-inhibiting compounds from plants. According to Pezzuto, "Of all the plants we've tested for cancer chemopreventive activity and all the compounds we've seen, this one has the greatest promise."

Enkele referenties en studies:

Melissa Q.B. McElderry, M.S., R.D. Grape Expectations: The Resveratrol Story 
Celotti E. Et al. Resveratrol content of some wines obtained from dried Valpolicella grapes: Recioto and Amarone. Journal of Chromatography A 730(1-2): 47-52, 1996. 

Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clinical Biochemistry 30:91-113, 1997. 

Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? European Journal of Endocrinology 138:619-620, 1998. 

Jang M. Et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218-220, 1997. 

Chanvitayapongs S, Draczynska-Lusiak B, Sun AY. Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuroreport 8:1499-1502, 1997. 

Rotondo S. Et al. Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. British Journal of Pharmacology 123:1691-1699, 1998. 

Clement MV. Et al. Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood 92:996-1002, 1998. 

Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W.W., Fong, H.H.S., Farnsworth, N.R., Kinghorn, A.D., Mehta, R.G., Moon, R.C. and Pezzuto, J.M. Science volume 10:218-221, 1997 

Een studie gepubliceerd in The British Journal of Cancer toont dat resveratrol, een stofje dat bv. veel voorkomt in rode wijn, asperges, bepaalde bessen enz. enz. door een verbinding te maken met een bepaald enzym ( CYP1B1) preventief is bij en wellicht bijdraagt aan de genezing van kanker. Hier eerst het abstract zoals gepubliceerd in the British Journal of Cancer en daaronder het persbericht met wat reacties zoals gepubliceerd bij de BBC. 

Abstract British Journal of Cancer (2002) 86, 774-778. DOI: 10.1038/sj/bjc/6600197

Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor. Piceatannol differs from resveratrol by having an additional aromatic hydroxy group. The enzyme CYP1B1 is overexpressed in a wide variety of human tumours and catalyses aromatic hydroxylation reactions. We report here that the cancer preventative agent resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol. The metabolite was identified by high performance liquid chromatography analysis using fluorescence detection and the identity of the metabolite was further confirmed by derivatisation followed by gas chromatography-mass spectrometry studies using authentic piceatannol for comparison. This observation provides a novel explanation for the cancer preventative properties of resveratrol. It demonstrates that a natural dietary cancer preventative agent can be converted to a compound with known anticancer activity by an enzyme that is found in human tumours. Importantly this result gives insight into the functional role of CYP1B1 and provides evidence for the concept that CYP1B1 in tumours may be functioning as a growth suppressor enzyme.

Hier het persbericht van de BBC:

A natural substance found in red wine, mulberries, peanuts and beansprouts may help prevent cancer. The molecule - called resveratrol - helps to fight the fungus that can blight many crops. 

But researchers have discovered that it is also converted in the body to a known anti-cancer agent that can selectively target and destroy cancer cells. 
Studies have suggested before that resveratrol might be cancer preventing - but this is the first time that scientists have gained a deeper insight into the underlying mechanism. Learning from nature in this way will help in our work to design drugs 

Professor Gerry Potter 
The research was carried out by Professor Gerry Potter and his team from Leicester's De Montfort University. 

Professor Potter said: "Learning from nature in this way will help in our work to design drugs which are selectively activated in a tumour and can form the basis of anti cancer-treatments. "Resveratrol is a defensive molecule against fungus in grapes and other crops, and is found at higher levels in those which have not been treated with man-made fungicides." 

Tumour enzyme 

The researchers found that resveratrol is processed by an enzyme called CYP1B1, which is found on a variety of different types of tumours. This converts resveratol into a toxic product called piceatannol. Previous research by the Leicester team has shown that this process is restricted to the tumour itself, limiting the toxicity to the cancer cells and serving to selectively destroy them. 

Scientists previously believed that CYP1B1 was a cause of cancer, because it is only found in tumours and not in healthy tissue. Far from causing cancer, they think the enzyme is there to fight it and the team is continuing research into ways to assist it in its work. 

Preventative properties 

Professor Potter said: "The belief that CYP1B1 is a cause of cancer is like blaming police for a crime just because they are on the scene. "We suspected this natural product might be beneficial for health and have cancer preventative properties. "This research shows just how it could prevent tumours developing by producing these anti-cancer molecules within the cancer cells themselves." 

Sir Paul Nurse, Joint Director General of Cancer Research UK said: "Specifically targeting cancer cells in order to destroy them is an important area of investigation which could ultimately lead to more effective drugs with fewer side effects." 

The research is published in the British Journal of Cancer. 








Hier wat bevindingen met wat links en daaronder een nieuw Engels artikel en studiebeschrijving. Allemaal over resveratol

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