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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resveratrol, a natural phytoalexin found in grapes, is well known for its presumed role in the prevention of heart disease, associated with red wine consumption. We show here that it is a remarkable inhibitor of ribonucleotide reductase and DNA synthesis in mammalian cells, which might have further applications as an antiproliferative or a cancer chemopreventive agent in humans.
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PMID:Resveratrol, a remarkable inhibitor of ribonucleotide reductase. 946 22

Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.
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PMID:Chemoprevention of cancer and cardiovascular disease by resveratrol. 1049 90

Epidemiologic evidence indicates that red wine may contain phenolic compounds which protect against heart disease and cancer. Resveratrol and quercetin are wine phenolics which possess antioxidant and antimutagenic effects. Resveratrol at 10 and 100 microM induced significant dose-dependent inhibition in human oral squamous carcinoma cell (SCC-25) growth and DNA synthesis. Quercetin exhibited a biphasic effect, stimulation at 1.0 and 10 microM and minimal inhibition at 100 microM in cell growth and DNA synthesis. Combining 50 microM of resveratrol with 10, 25 and 50 microM of quercetin resulted in gradual and significant increase in the inhibitory effect of the two compounds. Diluted red wine which contained only 1.6 microM of each of resveratrol and quercetin had significantly more inhibitory effect on cell growth, DNA synthesis and changes in cell morphology than each compound alone or in combination. We conclude that: (i) Resveratrol by itself or a combination of resveratrol and quercetin are effective inhibitors of SCC-25 growth and DNA synthesis. (ii) The presence of other wine phenolic phytochemicals enhance significantly the effect of resveratrol and quercetin on inhibition of cancer cell growth and DNA synthesis.
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PMID:The effect of red wine and its components on growth and proliferation of human oral squamous carcinoma cells. 1069 69

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural product occurring in grapes and various other plants with medicinal properties. The phenolic antioxidant has been identified as a potential cancer chemopreventative agent and its presence in red wine has been suggested to be linked to the low incidence of heart disease in some regions of France. Recently, however, resveratrol was reported to promote DNA fragmentation in the presence of copper ions (K. Fukuhara and N. Miyata, 1998, Bioorg. Med. Chem. Lett. 8, 3187-3192), prompting us to investigate this phenomenon in mechanistic detail. By acting as a reducing agent, resveratrol was found to promote hydroxyl-radical (*OH) formation by DNA-bound Cu(H) ions. However, in the presence of either ascorbic acid or glutathione (i.e., under more physiological conditions), the phenolic lost this property and behaved as an antioxidant. In the ascorbate system, resveratrol had no effect on the rate of *OH formation, but protected DNA from damage by acting as a radical-scavenging antioxidant. In contrast, in the glutathione system, resveratrol inhibited *OH formation via a novel mechanism involving the inhibition of glutathione disulfide formation. We have concluded, therefore, that the DNA-damaging properties of resveratrol, identified recently by Fukuhara and Miyata, will be of no significance under physiological conditions. To the contrary, we have demonstrated that the phenolic behaves as a powerful antioxidant, both via classical, hydroxyl-radical scavenging and via a novel, glutathione-sparing mechanism.
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PMID:Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. 1103 13

Stilbenes, in particular trans-resveratrol and its glucoside, are widely reported to be beneficial to health, having been shown to possess antioxidative, anticarcinogenic, and antitumor properties. Major dietary sources include grapes, wine, peanuts, and soy; however, they can also be introduced into the diet through Itadori tea, which has long been used in Japan and China as a traditional herbal remedy for heart disease and strokes. Analysis of grapes, peanuts, and Itadori tea shows that they contain mainly trans-resveratrol glucoside. In contrast, red wines are primarily a source of the aglycones cis- and trans-resveratrol. While peanuts and grapes contain low levels of the stilbenes, Itadori tea and red wine both supply relatively high concentrations of resveratrol. For people who do not consume alcohol, Itadori tea may be a suitable substitute for red wine. However, further study on the potential biological effects of other endogenous compounds in Itadori tea is required and there is also a need for more information on the absorption and in vivo biomedical actions of free and conjugated resveratrol.
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PMID:Plant foods and herbal sources of resveratrol. 1201 7

Resveratrol is a polyphenolic natural product that is present in red wine and peanuts and has inhibitory activity against inflammation, heart disease, and cancer. Here we describe its inhibition of human cytomegalovirus replication (IC50 = 1-2 microM). At least 50-fold higher concentrations of compound were required to produce cytotoxicity against growing or stationary human embryonic lung fibroblasts. Mechanism of action studies determined that resveratrol blocked virus-induced activation of the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3-kinase signal transduction as well as NF-kappaB and Sp1 transcription factor activation shortly following infection. Resveratrol prevented the appearance of immediate-early, early, and late viral proteins. Human cytomegalovirus DNA replication was reduced to undetectable levels by treatment with resveratrol, as were the second (late) phases of virus-induced phosphatidylinositol-3-kinase signaling and transcription factor activation. Resveratrol lost substantial antiviral activity when its addition was delayed until 4 h postinfection. Compound reversibility and preincubation studies were inconsistent with a virucidal mechanism of action. These data indicated that this compound likely operated during attachment and entry. We hypothesize that the primary molecular target for resveratrol may be blockage of epidermal growth factor receptor activation and its downstream effectors.
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PMID:3,4',5-Trihydroxy-trans-stilbene (resveratrol) inhibits human cytomegalovirus replication and virus-induced cellular signaling. 1530 37

trans-Resveratrol (t-RVT) has been shown to have a wide range of anti-inflammatory properties, some of which have been suggested to contribute to the molecular explanation of the French Paradox, a possible reason for the low incidence of heart disease in France. The ability of t-RVT to inhibit the production of reactive oxygen species (ROS) from monocytes (differentiated U937) was investigated using isoluminol, luminol, lucigenin, and 2',7'-dichlorofluorescein (DCF). t-RVT (0.1-50 microM) was found to significantly inhibit cellular ROS production stimulated by f-Met-Leu-Phe (fMLP), 12-phorbol 13-myristate, and arachidonic acid after a 1-h preincubation. The efficacy of t-RVT could be increased if it was added directly into the assay. NADPH-dependent superoxide production was measured in cell homogenates and t-RVT (10-50 microM) was found to have no effect on this activity. The majority of these redox probes require a peroxidase to be oxidized; therefore, the inhibitory effect of t-RVT on ROS measured by these probes is complicated by its ability to be oxidized by peroxidase enzymes and thus compete with the probe. t-RVT, known to be oxidized by the horseradish peroxidase (HRP)/H(2)O(2) system, was found to inhibit the HRP-dependent oxidation of the fluorescent probe DCF and the chemiluminescent probe isoluminol. However, using a redox probe that did not require oxidation by a peroxidase (lucigenin), significant inhibition was still observed. Moreover, the inhibitory effects of t-RVT on fMLP-induced ROS production correlated with significant inhibitory effects on fMLP-induced phosphatidylinositol 3-kinase (PI3K) activity at 50 microM and Akt phosphorylation (10-50 microM). Other known inhibitors of both PI3K and Akt were also found to inhibit this response. Therefore, inhibition of signaling through the PI3K to NADPH oxidase by t-RVT might represent an important anti-inflammatory mechanism.
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PMID:Inhibition of the respiratory burst by resveratrol in human monocytes: correlation with inhibition of PI3K signaling. 1592 84

Resveratrol is a phytoalexin produced in various plants like wine, peanut or pine in response to fungal infection or UV irradiation, but it is absent in members of the Brassicaceae. Moreover, resveratrol and its glucoside (piceid) are considered to have beneficial effects on human health, known to reduce heart disease, arteriosclerosis and cancer mortality. Therefore, the introduction of the gene encoding stilbene synthase for resveratrol production in rapeseed is a tempting approach to improve the quality of rapeseed products. The stilbene synthase gene isolated from grapevine (Vitis vinifera L.) was cloned under control of the seed-specific napin promotor and introduced into rapeseed (Brassica napus L.) by Agrobacterium-mediated co-transformation together with a ds-RNA-interference construct deduced from the sequence of the key enzyme for sinapate ester biosynthesis, UDP-glucose:sinapate glucosyltransferase (BnSGT1), assuming that the suppression of the sinapate ester biosynthesis may increase the resveratrol production in seeds through the increased availability of the precursor 4-coumarate. Resveratrol glucoside (piceid) was produced at levels up to 361 microg/g in the seeds of the primary transformants. This value exceeded by far piceid amounts reported from B. napus expressing VST1 in the wild type sinapine background. There was no significant difference in other important agronomic traits, like oil, protein, fatty acid and glucosinolate content in comparison to the control plants. In the third seed generation, up to 616 microg/g piceid was found in the seeds of a homozygous T3-plant with a single transgene copy integrated. The sinapate ester content in this homozygous T3-plant was reduced from 7.43 to 2.40 mg/g. These results demonstrate how the creation of a novel metabolic sink could divert the synthesis towards the production of piceid rather than sinapate ester, thereby increasing the value of oilseed products.
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PMID:Resveratrol glucoside (Piceid) synthesis in seeds of transgenic oilseed rape (Brassica napus L.). 1616 Aug 20

Much work has been carried out in recent years on the beneficial effect of phenolic compounds as natural antioxidants which help to neutralize free radicals. In fact, researchers have focused their attention on the pathological role of free radicals in a variety of diseases, among which the most important are atherosclerosis and cancer. Thus, among the components of the so-called 'Mediterranean Diet', phenolic compounds have received increased attention as epidemiological studies have shown that consumption of foods and beverages rich in phenolics is correlated with reduced incidence of heart disease. In this study, four phenolic compounds: (1) 3,4,5-trihydroxybenzoic acid (gallic acid); (2) trans 3,4',5-trihydroxystilbene (trans-resveratrol); (3) 3,3',4',5,7-pentahydroxyflavone (quercetin) and its glycoside (4) 3,3',4',5,7-pentahydroxyflavone-3-rutinoside (Rutin) have been subjected to antioxidant study by a fluorimetric assay. In this method, the rate of peroxidation induced by 2,2'-azobis (2-methylpropionamidine) dihydrochloride was monitored through the loss of fluorescence of the protein B-phycoerythrin (B-PE). Under appropriate conditions, the loss of B-PE fluorescence in the presence of reactive species is an index of oxidative damage of the protein. The inhibition of the action of reactive species by phenolic compounds, reflected in the protection against the loss of B-PE fluorescence in the fluorimetric assay, is a measure of its antioxidant capacity against the reactive species. The antioxidant effects of phenolic compounds have been investigated at different concentrations to relate activity to structural effects. It has been observed that the fluorescence decay due to peroxyl radical attack on B-PE decreases exponentially with time. As a reference compound for antioxidant capacity we used 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylicacid (trolox), a water soluble tocopherol analogue. This compound reacts rapidly with peroxyl radicals, and, until the trolox is consumed, no loss in phycoerythrin fluorescence is observed. A linear correlation of the net protection value with the concentration of trolox was demonstrated. The phenolic compounds studied react with peroxyl radicals in a similar way to trolox. Quercetin and rutin were shown to have strong antioxidant activities. The results obtained here are in agreement with previous studies confirming that quercetin is the most antioxidant of the four polyphenolics.
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PMID:Study of phenolic compounds as natural antioxidants by a fluorescence method. 1896 83

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a compound found in wine and is held responsible for a number of beneficial effects of red wine. Besides the prevention of heart disease and significant anti-inflammatory effects, resveratrol might inhibit tumor cell growth and even play a role in the aging process. We here describe the structure-activity relationship of resveratrol and analogues of resveratrol regarding the free radical scavenging and antitumor effects of this exciting natural compound. In addition, we have synthesized a number of analogues of resveratrol with the aim to further improve the beneficial effects of resveratrol. Our studies were based on the analysis of structural properties, which were responsible for the most important effects of this compound. Striking in vivo effects can be observed with hexahydroxystilbene (M8), the most effective synthetic analogue of resveratrol. We could show that M8 inhibits tumor as well as metastasis growth of human melanoma in two different animal models, alone and in combination with dacarbacine.
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PMID:Resveratrol and resveratrol analogues--structure-activity relationship. 2023 18


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