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Resveratrol

Distribution by Scientific Domains

Medical Sciences	52%
Life Sciences	23%
Chemistry	23%

Distribution within Medical Sciences

Pharmacology & Pharmaceutical Medicine	32%
Dermatology	9%
Oncology & Radiotherapy	7%
11 Other Subdomains	52%

Selected Abstracts

Targeting the development of resveratrol as a chemopreventive agent,

DRUG DEVELOPMENT RESEARCH, Issue 6 2010
Nian-Guang Li
Abstract Tumor development consists of several separate, but closely linked, stages: tumor initiation, promotion, and progression. This long and complex process provides opportunities for intervention both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Resveratrol, a polyphenolic compound found in many plant species, including grapes, peanuts, and various herbs, has recently been investigated intensely for its cancer chemopreventive property. The present work is an overview of the chemopreventive mechanisms of resveratrol in anti-initiation, anti-promotion, and anti-progression. These, together with the low toxicity of resveratrol, suggest promise for novel chemopreventive agents. However, the low bioavailability and rapid clearance of resveratrol from the circulation require the design of new resveratrol-like chemopreventive agents, the structural modifications and the structure,activity relationship of which are also discussed in this review. Drug Dev Res 71:335,350, 2010. © 2010 Wiley-Liss, Inc. [source]

Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2003
G. A. Losa
Abstract Background, We examined the effect of resveratrol (RS), a nonflavonoid polyphenolic phytoalexin found in grapes and red wine, and RS coincubated with the oxidant 2-deoxy-D-ribose (dR), on apoptosis and on the oxidative metabolic status of normal human peripheral blood mononuclear cells (PBMNCs) isolated ex vivo from healthy donors. Material and methods, Apoptosis was measured by changes of membrane permeability to propidium iodide (PI), plasma membrane exposure of phosphatidylserine (PS) and intracellular caspase activity. Oxidative status was assessed by recording the intracellular glutathione concentration (GSH), the activities of the enzymes y -glutamyltransferase (y- GT) and glutathione-S-transferase (GST), and intracellular lipid peroxidation (MDA). Results, Neither apoptotic nor oxidative parameters were affected by culturing PBMNCs in medium containing RS up to 20 µM for 5 days, while the frequency of cells with intermediate permeability to PI (17% ± 5) increased at 50 µM of RS. Thus resveratrol was slightly toxic, but there was little apoptosis in these cells. Peripheral blood mononuclear cells were also grown first in medium plus RS for 24 h and then for 96 h in medium containing RS plus 10 mM of dR, an oxidant sugar that is apoptogenic for human lymphocytes. The apoptotic changes triggered by dR were counteracted by the phytoalexin in a dose-dependent manner, but RS activity was absent at the lowest concentration (5 µM) and significantly reduced at the highest concentration used (50 µM). In PBMNCs coincubated with 20 µM of RS and 10 mM of dR the antioxidant effect of RS manifested with a significant reduction of caspases-3, -8, y- GT, GST activities and MDA content. Conclusions, Peripheral blood mononuclear cells acquire antioxidant capacity when treated with RS. Grape resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases. [source]

Resveratrol inhibits proliferation of human epidermoid carcinoma A431 cells by modulating MEK1 and AP-1 signalling pathways

EXPERIMENTAL DERMATOLOGY, Issue 7 2006
Arianna L. Kim
Abstract:, Resveratrol (trans -3,4,,5-trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found in grapes, and has been shown to inhibit the growth of various types of cancer cells. We investigated the mechanism of the antiproliferative effect of resveratrol in A431-transformed keratinocytes harbouring mutant p53, and show that it is accompanied by G1 cell cycle arrest, which coincides with a marked inhibition of G1 cell cycle regulatory proteins, including cyclins A and D1 and cyclin-dependent kinase (CDK)6 and p53-independent induction of p21WAF1. Cell cycle arrest was also associated with the accumulation of hypophosphorylated Rb and p27KIP1. Resveratrol inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)1 > extracellular signal-regulated protein kinase (ERK)1/2 signalling, downregulated c-Jun, and suppressed activating protein (AP)-1 DNA-binding and promoter activity. In addition, the inhibition of MEK1 > ERK1/2 signalling appears to be independent of retinoblastoma protein (pRb) hypophosphorylation in A431 cells, as PD098059 did not suppress pRb phosphorylation. Our results demonstrate that resveratrol affects multiple cellular targets in A431 cells, and that the downregulation of both AP-1 and pRb contributes to its antiproliferative activity in these cells. [source]

Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol

FEMS YEAST RESEARCH, Issue 1 2003
John V.W. Becker
Abstract The stilbene resveratrol is a stress metabolite produced by Vitis vinifera grapevines during fungal infection, wounding or UV radiation. Resveratrol is synthesised particularly in the skins of grape berries and only trace amounts are present in the fruit flesh. Red wine contains a much higher resveratrol concentration than white wine, due to skin contact during fermentation. Apart from its antifungal characteristics, resveratrol has also been shown to have cancer chemopreventive activity and to reduce the risk of coronary heart disease. It acts as an antioxidant and anti-mutagen and has the ability to induce specific enzymes that metabolise carcinogenic substances. The objective of this pilot study was to investigate the feasibility of developing wine yeasts with the ability to produce resveratrol during fermentation in both red and white wines, thereby increasing the wholesomeness of the product. To achieve this goal, the phenylpropanoid pathway in Saccharomyces cerevisiae would have to be introduced to produce p -coumaroyl-CoA, one of the substrates required for resveratrol synthesis. The other substrate for resveratrol synthase, malonyl-CoA, is already found in yeast and is involved in de novo fatty-acid biosynthesis. We hypothesised that production of p -coumaroyl-CoA and resveratrol can be achieved by co-expressing the coenzyme-A ligase-encoding gene (4CL216) from a hybrid poplar and the grapevine resveratrol synthase gene (vst1) in laboratory strains of S. cerevisiae. This yeast has the ability to metabolise p -coumaric acid, a substance already present in grape must. This compound was therefore added to the synthetic media used for the growth of laboratory cultures. Transformants expressing both the 4CL216 and vst1 genes were obtained and tested for production of resveratrol. Following ,-glucosidase treatment of organic extracts for removal of glucose moieties that are typically bound to resveratrol, the results showed that the yeast transformants had produced the resveratrol ,-glucoside, piceid. This is the first report of the reconstruction of a biochemical pathway in a heterologous host to produce resveratrol. [source]

Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2007
Sameer Sharma
Abstract Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor- , (TNF- ,) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF- , levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain. [source]

Screening of phytochemicals in fresh lamb meat patties stored in modified atmosphere packs: influence on selected meat quality characteristics

INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2010
Ava Isabel Andrés Nieto
Abstract This study was carried out to determine the antioxidant activity of phytochemicals and plant extracts in fresh lamb patties. Quality indices such as colour (Hunter L* a* b*), lipid oxidation (TBARS) and pH were measured over an 8-day storage period. Resveratrol, citroflavan-3-ol, olive leaf extract and Echinacea purpurea were added to raw minced M. longissimus dorsi lamb patties, at concentrations ranging from 0,400 mg kg,1 lamb meat, stored in high oxygen modified atmospheres packs (75% O2:25% CO2) for up to 8 days at 4 °C. The pH of the lamb meat was not significantly affected by the addition of the phytochemicals and plant extracts examined (P > 0.05). Resveratrol and citroflavan-3-ol decreased (P < 0.05) lipid oxidation in raw lamb patties during storage and increased a* values (P < 0.05), relative to controls. By contrast, olive leaf extract and Echinacea purpurea did not exhibit antioxidant activity or promote higher a* values relative to controls. Results obtained demonstrate potential for the development of functional meats using plant extracts such as resveratrol and citroflavan-3-ol. [source]

Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat-mediated long terminal repeat transactivation

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2010
Hong-Sheng Zhang
Abstract Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV-1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide+ (NAD+)-dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the conversion of nicotinamide into NAD+, which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat-regulated SIRT activity was studied in Hela-CD4-,-gal (MAGI) cells. We demonstrated that Tat caused NAD+ depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat-induced NAD+ depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat-induced inhibition of SIRT1 activity was potentiated in Nampt-knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat-induced HIV-1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat-induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV-1 infection. J. Cell. Biochem. 110: 1464,1470, 2010. © 2010 Wiley-Liss, Inc. [source]

Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation

JOURNAL OF COSMETIC DERMATOLOGY, Issue 1 2008
Richard A Baxter MD
Summary Resveratrol, an antioxidant polyphenol from red wine, has been the subject of intense interest in recent years due to a range of unique anti-aging properties. These include cardiovascular benefits via increased nitric oxide production, down-regulation of vasoactive peptides, lowered levels of oxidized low-density lipoprotein, and cyclooxygenase inhibition; possible benefits on Alzheimer's disease by breakdown of beta-amyloid and direct effects on neural tissues; phytohormonal actions; anticancer properties via modulation of signal transduction, which translates into anti-initiation, antipromotion, and antiprogression effects; antimicrobial effects; and sirtuin activation, which is believed to be involved in the caloric restriction-longevity effect. Here we report a resveratrol-based skin care formulation, with 17 times greater antioxidant activity than idebenone. The role of resveratrol in prevention of photoaging is reviewed and compared with other antioxidants used in skin care products. [source]

Cis ,-viniferin: A New Antifungal Resveratrol Dehydrodimer from Cyphostemma crotalarioides Roots

JOURNAL OF PHYTOPATHOLOGY, Issue 1 2000
A. E. A. Bala
Abstract Six antifungal constituents were isolated from the roots of Cyphostemma crotalarioides (Vitaceae): a new product, Cis - , -viniferin 3, along with five known compounds: trans -resveratrol I and its oligomers: trans , -viniferin 2, gnetin C 4, pallidol 5 and gnetin E 6. It is the first time such compounds have been reported in this plant species. The roots tissues were found to be rich in other resveratrol oligomers, however, the available amounts of the other purified products did not allow structure investigations. No fungicidal activity was detected in the leaves of this plant. Zusammenfassung Cis - , -Viniferin: Ein neues antifungal wirkendes Resveratrol-Dehydrodimer aus den Wurzeln von Cyphostemma crotalarioides Aus den Wurzeln von Cyphostemma crotalarioides (Vita-ceae) wurden sechs antifungal wirkende Bestandteile isoliert: ein neues Produkt, cis - , -Viniferin 3, neben fünf bekannten Verbindungen: trans -Resveratrol 1 und seine Oligomete: trans - , -Viniferin 2, Gnetin C 4, Pallidol 5 und Gnetin E 6. Dies ist der erste Bericht über das Aufreten solcher Verbindungen in dieser Pflanzenart. Die Wurzel-gewebe waren reich an weiteren Resveratrol-Oligomeren. doch die Ausbeuten der anderen gereinigten Substanzen erlaubten keine Strukturbestimmungen. In den Bláttern dieser Pflanze wurde keine fungizide Aktivität festgestellt. [source]

The Biological Responses to Resveratrol and Other Polyphenols From Alcoholic Beverages

ALCOHOLISM, Issue 9 2009
Lindsay Brown
Although excessive consumption of ethanol in alcoholic beverages causes multi-organ damage, moderate consumption, particularly of red wine, is protective against all-cause mortality. These protective effects could be due to one or many components of the complex mixture of bioactive compounds present in red wine including flavonols, monomeric and polymeric flavan-3-ols, highly colored anthocyanins as well as phenolic acids and the stilbene polyphenol, resveratrol. The therapeutic potential of resveratrol, firstly in cancer chemoprevention and then later for cardioprotection, has stimulated many studies on the possible mechanisms of action. Further indications for resveratrol have been developed, including the prevention of age-related disorders such as neurodegenerative diseases, inflammation, diabetes, and cardiovascular disease. These improvements are remarkably similar yet there is an important dichotomy: low doses improve cell survival as in cardio- and neuro-protection yet high doses increase cell death as in cancer treatment. Fewer studies have examined the responses to other components of red wine, but the results have, in general, been similar to resveratrol. If the nonalcoholic constitutents of red wine are to become therapeutic agents, their ability to get to the sites of action needs to be understood. This mini-review summarizes recent studies on the possible mechanisms of action, potential therapeutic uses, and bioavailability of the nonalcoholic constituents of alcoholic beverages, in particular resveratrol and other polyphenols. [source]

Cover Picture , Mol.

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2008
Nutr.
Regular issues provide a wide range of research and review articles covering all aspects of Molecular Nutrition & Food Research. Selected topics of issue 6 are: Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Lycopene inhibits growth of human colon cancer cells Resveratrol inhibits migration and invasion of human breast-cancer cells Quantification of the thaumatin-like kiwi allergen by a monoclonal antibody-based ELISA Short-term effects of a low glycemic load diet on hormonal markers of acne [source]

Resveratrol: Preventing properties against vascular alterations and ageing

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2005
Dominique Delmas
Abstract Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases. [source]

Potential of resveratrol in anticancer and anti-inflammatory therapy

NUTRITION REVIEWS, Issue 8 2008
Chibuike C Udenigwe
Phytochemicals present in food have shown significant prospects in the treatment and management of a vast array of human diseases. Resveratrol is a stilbene-type aromatic phytoalexin predominantly found in grapes, peanuts, berries, turmeric, and other food products. Resveratrol has been reported to exhibit several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans. Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases. [source]

Resveratrol Imparts Photoprotection of Normal Cells and Enhances the Efficacy of Radiation Therapy in Cancer Cells,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008
Shannon Reagan-Shaw
Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions. [source]

Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult

PHYTOTHERAPY RESEARCH, Issue S1 2010
Kanti Bhooshan Pandey
Abstract Resveratrol is a natural polyphenolic compound found largely in the skin of red grapes. Growing evidence suggests that resveratrol may play an important role in the prevention of many human diseases. Many of the biological actions of this polyphenol have been attributed to its antioxidant properties. The present study was undertaken to evaluate the effect of resveratrol on intracellular reduced glutathione (GSH) and membrane sulphydryl groups in erythrocytes subjected to oxidative stress in vitro by incubating with t-BHP (10 µm). The study was aimed to test the efficacy of the antioxidant effect of resveratrol on human erythrocytes. Subjecting erythrocytes to oxidative stress (in vitro) by incubating them with t-BHP (10 µm) caused a significant decrease in the intracellular GSH level and membrane ,SH content compared with basal values. Incubation of erythrocytes/membranes with resveratrol (1,100 µm final conc) resulted in significant protection against the t-BHP-induced oxidative stress as evidenced by the increase in GSH level and membrane ,SH content. It was observed that the effect of resveratrol is dose/concentration and time-dependent. Since resveratrol is naturally present in many fruits and vegetables, a diet rich in resveratrol may provide protection against degenerative diseases. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Resveratrol attenuates 1,2-dimethylhydrazine (DMH) induced glycoconjugate abnormalities during various stages of colon carcinogenesis

PHYTOTHERAPY RESEARCH, Issue 8 2009
Murugan Sengottuvelan
Abstract Although a myriad of health promoting effects has been attributed to resveratrol (Res) (3,5,4,-trihydroxy- trans -stilbene), a phytoalexin, the most interesting is its anticancer property. The aim of this work was to elucidate the effectiveness of Res against cellular transformation (glycoconjugate alterations) initiated by 1,2-dimethylhydrazine (DMH), a colon specific carcinogen. Group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body weight orally every day), rats in groups 3,6 were treated weekly with DMH (20 mg/kg body weight, subcutaneously × 15 times). In addition, groups 4,6 received Res (as in group 2) in three dietary regimens: initiation (I), post-initiation (PI) and entire period (EP). At the end of the 30 week experimental period in DMH alone exposed rats, altered levels of glycoconjugates (total hexoses, fucose, hexosamine and sialic acid) were observed in liver, intestine and colon tissues. Of the three dietary regimens of Res, the entire period supplementation significantly (p < 0.01) modulated the levels of glycoconjugates and reduced the incidence of adenoma and adenocarcinoma. These findings suggest that Res may extend its chemopreventive effect by restoring the alteration in glycoconjugates that are thought to be involved in the colonic malignant transformation process in this experimental model. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes ,

PHYTOTHERAPY RESEARCH, Issue 10 2008
Srujana Rayalam
Abstract Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200 µM resveratrol decreased cell viability dose-dependently by 23 ± 2.7%, and 75.3 ± 2.8% (p < 0.0001), respectively, after 48 h treatment, and 100 µM resveratrol increased apoptosis by 76 ± 8.7% (p < 0.0001). Resveratrol at 25 and 50 µM decreased lipid accumulation in maturing preadipocytes significantly by 43 ± 1.27% and 94.3 ± 0.3% (p < 0.0001) and decreased cell viability by 25 ± 1.3% and 70.4 ± 1.6% (p < 0.0001), respectively. In order to understand the anti-adipogenic effects of resveratrol, maturing 3T3-L1 preadipocytes were treated with 25 µM resveratrol and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Resveratrol down-regulated the expression of PPAR,, C/EBP,, SREBP-1c, FAS, HSL, LPL and up-regulated the expression of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2). These results indicate that resveratrol may alter fat mass by directly affecting cell viability and adipogenesis in maturing preadipocytes and inducing apoptosis in adipocytes and thus may have applications for the treatment of obesity. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Activity of NADPH-Cytochrome P-450 Reductase of the Human Heart, Liver and Lungs in the Presence of (-)-Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro Study

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2005
Jaroslaw Dudka
The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine. [source]

Antioxidative and Prooxidative Action of Stilbene Derivatives

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2000
Toshiaki Miura
The effects of stilbene derivatives, including resveratrol, diethylstilboestrol and stilbene, as antioxidants or prooxidants were examined. Resveratrol and diethylstilboestrol, but not stilbene, strongly inhibited NADPH- and adenosine 5,-diphosphate (ADP)-Fe3+ -dependent lipid peroxidation at the initial and propagation stages. In addition, phenolic stilbenes also inhibited ultraviolet light-induced lipid peroxidation. Resveratrol and diethylstilboestrol efficiently scavenged 2,2,-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals. However, 2,2,-diphenyl-p-picrylhydrazyl radicals were trapped only by resveratrol, but not by diethylstilboestrol. These results suggest that the inhibitory effect of phenolic stilbenes on lipid peroxidation was due to their scavenging ability of lipid peroxyl and/or carbon-cantered radicals. Resveratrol efficiently reduced ADP-Fe3+, but not EDTA-Fe3+. Stilbenes and diethylstilboestrol did not reduce either ADP-Fe3+ or EDTA-Fe3+. The strand breaks of DNA were stimulated during the interaction of resveratrol with ADP-Fe3+ in the presence of H2O2. These results suggest that phenolic stilbenes act as antioxidants of membrane lipids and that resveratrol has a prooxidative effect DNA damage during interaction with ADP-Fe3+ in the presence of H2O2. [source]

Resveratrol is efficiently glucuronidated by UDP-glucuronosyltransferases in the human gastrointestinal tract and in Caco-2 cells

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2006
Nicole Sabolovic
Abstract Resveratrol (3, 5, 4,-trihydroxy- trans -stilbene), a natural polyphenol present in grapes and peanuts, has been reported to exert a variety of potentially therapeutic effects. The aim of this study was to determine the contribution of the gastrointestinal (GI) tract to the glucuronidation of this compound and its cis -isomer, which also occurs naturally. For this purpose, glucuronidation of the two resveratrol isomers was investigated in human microsomes prepared from: stomach, duodenum, four segments of the remaining small intestine (S-1 to S-4) and colon, and from the human intestinal cell lines Caco-2 and PD-7. cis - and trans -Resveratrol were efficiently glucuronidated in the GI tract with the formation of both 3- O - and 4,- O -glucuronides, however, the two stereoisomers were glucuronidated at different rates depending on the donor and the segment considered. Microsomes prepared from Caco-2 and PD-7 cells also efficiently glucuronidated cis -resveratrol and, to a lesser extent, the trans -isomer, however, only the 3- O -glucuronide was formed. Among the UDP-glucuronosyltransferases (UGT) that are known to be expressed in the GI tract, the isoforms UGT1A1, 1A6, 1A8, 1A9 and 1A10 were active in glucuronidating trans - and/or cis -resveratrol. The results demonstrate that the GI tract may contribute significantly to the first pass metabolism of these naturally occurring polyphenols. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo

CANCER SCIENCE, Issue 2 2010
Yu Bai
Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP-ribose) polymerase degradation. Treatment with resveratrol led to G1 phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin-dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor-2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer. (Cancer Sci 2009) [source]

Cardiovascular Protective Effects of Resveratrol

CARDIOVASCULAR THERAPEUTICS, Issue 3 2004
Silvia Bradamante
ABSTRACT Resveratrol (3,4,,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans. [source]

Protective Effects of Resveratrol and its Analogues against Free Radical-Induced Oxidative Hemolysis of Red Blood Cells,

CHINESE JOURNAL OF CHEMISTRY, Issue 11 2002
Jian-Guo Fang
Abstract The in vitro oxidative hemolysis of human red blood cells (RBCs) was used as a model to study the free radical-induced damage of biological membranes and the protective effect of resveratrol (3,5,4,-trihydroxy-trans-stilbene, 1) and its analogues, i. e., 4-hydroxy- trans -stilbene (2), 3, 5- dihydroxytrans -stilbene (3), 3,4-dihydroxy- trans -stilbene (4), 4,4,-dihydroxy- trans -stilbene (5) and 2, 4, 4,-trihydroxy- trans -stilbene (6). The hemolysis of RBCs was induced by a water-soluble free radical initiator 2, 2,-azobis (2-amidinopropane hydrochloride) (AAPH). It was found that addition of AAPH at 37 °C to the suspension of RBCs caused fast hemolysis after a short period of inhibition period, and addition of 1,6 significantly suppressed the hemolysis. Compound 4 which bears an ortho -dihydroxyl functionality showed much more effective anti-hemolysis activity than that of resveratrol and the other analogues. [source]

Targeting the development of resveratrol as a chemopreventive agent,

Nonaqueous capillary electrophoretic separation of polyphenolic compounds in wine using coated capillaries at high pH in methanol

ELECTROPHORESIS, Issue 24 2003
Zuzana Demianová
Abstract Nonaqueous capillary electrophoretic separation of a group of flavonoids (quercetin, myricetin, catechin, epicatechin) and resveratrol in wine was investigated in methanol at high pH. Malonate background electrolyte (pH* 13.5, ionic strength I = 14.2 mmol/L) provided highly repeatable separations of the analytes. Tests of untreated and coated (poly(glycidylmethacrylate- co - N -vinylpyrrolidone)) capillaries showed the analysis to be faster (6.5 min vs. 25 min) and the repeatability better in the coated capillaries. The coating procedure was simple and highly repeatable and the coating was stable during 40,45 runs. Determination of the last migrating peaks (epicatechin, resveratrol and catechin) was achieved merely by evaporating the wine samples and reconstituting the residue in methanol. For determination of the first migrating peaks (quercetin and myricetin) the samples were submitted to solid-phase extraction in C8 cartridges. [source]

Interaction of stilbene compounds with human and rainbow trout estrogen receptors

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008
Denina Bobbie Dawn Simmons
Abstract Compounds with stilbene structures are widely used as pharmaceuticals and personal care products (PPCPs) and are present in plants. A suite of stilbene-related compounds, including PPCPs and plant-derived compounds were tested in vitro for interactions with the human and rainbow trout estrogen receptors and in vivo with rainbow trout using vitellogenin levels as a biomarker. Among the compounds with antagonistic activity, the common structural similarity was (in addition to the stilbene backbone) the presence of 4-hydroxy substitution. Stilbene-related compounds found to act as inhibitors at the estrogen receptor included the plant-derived compound resveratrol and two formulations of fluorescent whitening agents used in detergents, 4,4,-bis(2-sulfostyryl)biphenyl and diaminostilbene-1. In the yeast estrogenicity screening assay, the concentrations which caused a 50% inhibition in estrogenic response (IC50s) with the human estrogen receptor ranged from 2.56 × 10,6 to 2.56 × 10,6 M. In the rainbow trout estrogen receptor assay, the IC50s ranged from 7.75 × 10,8 to 1.11 × 10,5 M. However, in the in vivo rainbow trout vitellogenin assay, tamoxifen was the only stilbene of the compounds tested to have a significant effect as an inhibitor of estrogenicity. [source]

Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells

Physical-chemical characteristics and oxidative stability of oil obtained from lyophilized raspberry seed

EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 11 2009
Aleksandra, urovi
Abstract Fresh raspberry (Rubus idaeus), cultivar Willamette, was freeze-dried (lyophilization). A byproduct of lyophilization is "fine dust" of raspberry consisting of finely ground raspberry fruit body and seed. The seeds were separated. The seed oil was isolated and its physical and chemical characteristics were determined. Parameters that characterize the seed and quality of the oil were examined, including fatty acid composition, oxidative stability under different storage conditions, and radical-scavenging activity. The fatty acid composition was determined by GC/FID and the contents of the dominant fatty acids were found as: oleic 16.92%, linoleic 54.95%, and ,-linolenic acid 23.97%. The oxidative stability of the oil was poor. The induction period by Rancimat test at 100,°C was 5.2,h. The radical-scavenging activity is similar to that of resveratrol [1,3-benzenediol 5-(1E -2-4-hydroxy-phenyl-ethyl)]. Although this product is used in the candy industry, it would be far more useful if raspberry oil of satisfactory quality could be extracted. This paper demonstrates that sifted lyophilized seeds can be used for the extraction of oils. This process allows for maximal usage of the byproducts, reduces losses and it increases the development of new products. [source]

Solid-Phase Reactive Chromatography (SPRC): A New Methodology for Wittig and Horner,Emmons Reactions on a Column under Microwave Irradiation

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2010
Saada C. Dakdouki
Abstract A new methodology named solid-phase reactive chromatography (SPRC), which combines reaction, separation, and purification into a single unit for the preparation of small samples, is described. This method was illustrated in the synthesis of some natural bioactive compounds, namely, methoxylated analogues of resveratrol, alkylresorcinols, and 5-aryl-2,4-pentadienoates, over a column of alumina-KF under microwave irradiation by using the Wittig and Horner,Emmons reactions. This approach permitted the preparation of the target olefins with high purity and good to excellent yields in short reaction times. [source]