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PubMed1998

Polyphenols inhibit promotional phase of tumorigenesis: relevance of superoxide radicals.

Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA) offer considerable promise as anticarcinogens. The role of these dietary polyphenols was investigated in the promotional phase of carcinogenesis. Topical application of polyphenols simultaneously with phorbol-12-myristate-13-acetate (PMA) or mezerein resulted in significant protection against 7,12-dimethyl-benz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine peritoneal macrophages with the tumor promoters resulted in stimulation of superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid were stronger inhibitors of PMA- and mezerein-induced superoxide anion radical than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)-14C]glycerol- or [methyl-14C]choline chloride-labeled resident or thioglycollate-elicited macrophages with PMA and mezerein led to accumulation of radioactive diacylglycerol equivalents. The polyphenols were capable of inhibiting these releases.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Is the C-terminal region of bradykinin the binding site of polyphenols?

Bradykinin is a bioactive hormone involved in a variety of physiological processes. In various solvents, this peptide adopts beta-turn structures. The C-terminal turn is a structural feature for the receptor affinity of agonists and antagonists while the N-terminal turn might be important for antagonistic activities. Polyphenols like dimeric proanthocyanidin B3 interact with the peptide. Thus to investigate the effects of polyphenols on bradykinin activity and structure, we studied the interaction in the structuring solvent DMSO which can be a close mimic of aqueous physiological environments like receptor-binding sites. Bradykinin alone presented a folded structure with two turns. B3 interacted with the peptide C-terminus and involved the loss of the bend structure of this region, while the N-terminus turn was maintained. Numerous studies have shown that polyphenolic molecules can act upon various biological targets, and the formation of this type of complex might be one of the possible modes of action.

Anthocyanins↗
PubMed2006

The effect of exercise and training status on platelet activation: do cocoa polyphenols play a role?

Sedentary and trained men respond differently to the same intensity of exercise, this is probably related to their platelet reactivity and antioxidant capacity. There is growing interest in the utilization of antioxidant-rich plant extracts as dietary food supplements. The aim of this study was to investigate the effect of an acute bout of sub maximal exercise on platelet count and differential response of platelet activation in trained and sedentary subjects and to observe if cocoa polyphenols reverse the effect of exercise on platelet function. The practical significance of this study was that many sedentary people engage in occasional strenuous exercise that may predispose them to risk of heart disease. Fasting blood samples were collected from 16 male subjects, pre and post 1-h cycling exercise at 70% of maximal aerobic power (VO2max) before and after consumption of cocoa or placebo. Agonist stimulated citrated whole blood was utilized for measuring platelet aggregation, adenosine triphosphate (ATP) release and platelet activation. Baseline platelet count (221 +/- 33 x 10(9)/L) and ATP release (1.4 +/- 0.6 nmol) increased significantly (P < 0.05) after exercise in all subjects. Baseline platelet numbers in the trained were higher (P < 0.05) than in the sedentary (235 +/- 37 vs. 208 +/- 34 x 10(9)/L), where as platelet activation in trained was lower (P < 0.05) than sedentary (51 +/- 6 vs. 59 +/- 5%). Seven days of cocoa polyphenol supplementation had little effect on any of the parameters measured. We conclude that trained subjects show decreased activation of stimulated platelets when compared to the sedentary subjects and short-term cocoa polyphenol supplementation did not decrease platelet activity in response to exercise independent of prior training status.

Adolescent↗
PubMed2005

Consumer labels can convey polyphenolic content: implications for public health.

Polyphenolics are a large group of related substances. Many of these, in fact much of that found in food, is composed of processing-derived substances too complex for complete identification. Recent studies have suggested likely benefits for diets high in polyphenols, particular in reducing heart disease mortality, but other benefits have also been suggested. A consumer label based on the major polyphenolic classes is both manageable and fairly informative as most foods do not contain all possible classes. Differences between class member can be significant, but data on individual substances is impractical and no data is certainly less informative. Equivalency scales may be useful but may skew content of many foods towards the high-equivalency substances, even while the full beneficial effects of each individual substance is poorly described.

Community Participation↗
PubMed2003

Simultaneous detection of the antioxidant and pro-oxidant activity of dietary polyphenolics in a peroxidase system.

The ability to reduce the peroxidase (myeloglobin/H2O2)-generated ABTS*+ [2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) radical cation] has been used to rank the antioxidant activity of various agents including dietary flavonoids and chalcones. Surprisingly, we found that in the presence of catalytic concentrations of the phenol B-ring containing flavonoids, apigenin, naringenin and the chalcone phloretin, the formation of the ABTS*+ was initially increased. The enhanced formation of the ABTS*+ was attributed to the peroxidase/H2O2 mediated generation of polyphenolic phenoxyl radicals that were able to co-oxidize ABTS. The relative ABTS*+ generating ability of these dietary polyphenolics correlated with their ability to co-oxidize NADH to the NAD* radical with the resultant generation of superoxide. This pro-oxidant activity was not observed for either luteolin or eriodyctiol, which are B-ring catecholic analogues of apigenin and naringenin, respectively, suggesting that these antioxidants are incapable of the transition metal-independent generation of reactive oxygen species. This pro-oxidant activity of the polyphenolics therefore needs to be taken into account when quantifying antioxidant activity.

Antioxidants↗
PubMed2006

Polyphenols from green tea and pomegranate for prevention of prostate cancer.

Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in North America with similar trends in many Western countries. Geographic, epidemiological and laboratory studies suggest a role for dietary constituents in the etiology as well as prevention of PCa. The rising incidence of PCa in several countries appears to be coincidental with adoption of western lifestyle. Increase in the incidence of PCa has also been found in Asian populations migrating to the west. These facts give numerous leads to explore testable PCa prevention strategies. There is growing evidence in support of use of dietary ingredients in prevention and treatment of PCa. While substantial data exists in favor of use of polyphenols from tea as PCa chemopreventive agent, interest in anti-cancer properties of polyphenols from pomegranate has recently emerged. This review summarizes current literature on the effects of polyphenols from green tea and pomegranate against PCa.

Anticarcinogenic Agents↗
PubMedDate not supplied

Prevention of carcinogenesis by tea polyphenols.

Tea, an extract of the leaves of the plant Camellia sinensis, has been considered a medicine and healthful beverage for ages. The beneficial effects of tea are thought to be due to its polyphenolic components. Herein, we discuss the present status of tea as a possible cancer chemopreventive agent, covering basic chemistry and biochemical activity of tea, pharmacokinetics of major tea components, studies in animal and cell lines, epidemiological investigations, and future challenges. Tea is one of the few chemopreventive agents known to have protective effects at different stages of the carcinogenic process. Tea constituents may inhibit this process by modulating signal transduction pathways leading to the inhibition of cell proliferation and transformation and enhancement of apoptosis. These activities may or may not be due to the antioxidative activity of tea polyphenols. The bioavailability and tissue levels of tea polyphenols is a key topic to be studied in order to understand the mechanisms of action of tea and its possible protection against cancer in humans.

Animals↗
PubMed2004

Polyphenolic antioxidants enhance IgE production.

Epidemiological data showed that total IgE and IL-4 levels in cigarette smokers were elevated, comparable to those in the asthmatics. The etiological agent(s) elevating IgE production are not clear. We evaluate whether tobacco polyphenols potentiate IgE production in a rodent model. Mice were fed with rutin or CGA in drinking water during antigen sensitization, followed by antigenic challenge i.p. in alum. CGA and rutin were also delivered in a bolus intraperitoneally or intranasally along with antigens during immunization. Antigen-specific IgE and IgG responses were measured. Enhancement of total IgE responses via i.p. and drinking routes can be achieved at concentrations as low as 0.1% CGA. Furthermore, IgG1 responses but not IgG2a and IgG2b were augmented, indicating a Th2 type of response by CGA. Moreover, both antigen-specific and serum IgE production can be achieved when CGA and antigenic challenges were delivered intranasally in the absence of alum. In contrast, nicotine does not enhance antigen-specific IgE production, and only marginally affects serum IgE levels. The more polarized Th2 development in CGA-treated mice may account for enhancement of both antigen-specific and total IgE responses. High levels of IL-4 but not IFN-gamma or IL-12, were observed in antigen-challenged mesenteric lymph nodes (MLN) cultures from CGA-treated mice. In contrast, significant levels of IL-4, IL-12, and IFN-gamma were observed in antigen-challenged cultures from nicotine-treated mice. This study shows that tobacco polyphenols, CGA and rutin potentiated IgE production in vivo. Polyphenolic antioxidants enhance Th2 development. We propose that IgE production and T cell dichotomy may be critically influenced by the redox microenvironment. Enhanced Th2 development and IgE production henceforth may counteract more severe Th1-mediated tissue damage triggered by environmental oxidative stress.

Animals↗
PubMed2005

Antioxidative effects of polyphenols in leaves of Houttuynia cordata on protein fragmentation by copper-hydrogen peroxide in vitro.

The leaves of Houttuynia cordata have been traditionally used as medicinal foods in East Asia. However, there have been few data about the biological effects. The antioxidative effects of polyphenols in the leaves of H. cordata were investigated on protein fragmentation by copper-hydrogen peroxide in vitro. The total polyphenol content in the leaves of H. cordata was 1.14%. The condensed tannin content was 2.46% by vanillin assay and 0.54% by proanthrocyanidin assay. The polyphenols in the leaves of H. cordata inhibited bovine serum albumin fragmentation by copper-hydrogen peroxide. These results demonstrated that the leaves of H. cordata have antioxidative effects on biological damage such as protein fragmentation.

Antioxidants↗
PubMed2005

An investigation of the analgesic and anti-inflammatory effects of Nigella sativa seed polyphenols.

Extracts obtained from the seeds of Nigella sativa are used as a spice or remedy for the treatment of various inflammatory diseases. The purpose of this study was to examine the analgesic and anti-inflammatory effects of its polyphenols. N. sativa seed polyphenols were prepared, and analgesic and anti-inflammatory effects were studied in mice and rats using the acetic acid-induced writhing, formalin, light tail flick, carrageenan-induced paw edema, and croton oil-induced ear edema tests. In the acetic acid-induced writhing test, oral administration of N. sativa polyphenols (NSP) decreased the number of abdominal constrictions. Both oral and intraperitoneal administration of NSP significantly suppressed in a dose-dependent manner the nociceptive response in the early and late phases of the formalin test, and the effect on the late phase was more pronounced. Pretreatment with naloxone failed to reverse the analgesic activity of NSP in this test. NSP did not produce a significant analgesia in the light tail flick test in mice. Oral administration of NSP did not produce a significant reduction in carrageenan-induced paw edema. However, when injected intraperitoneally, NSP inhibited paw edema in a dosedependent manner. NSP when applied topically failed to reduce croton oil-induced ear edema. These results suggest that NSP have analgesic and anti-inflammatory effects. The lack of analgesic effect of NSP in the light tail flick test and also the failure of naloxone to reverse the analgesia in the formalin test reveal that mechanisms other than stimulation of opioid receptors are involved.

Acetic Acid↗
PubMed1990

Influence of folate status and polyphenol intake on thiamin status of Irish women.

The relationship of folate status and polyphenol intake to thiamin status was studied in 80 randomly selected elderly and young Irish women, with key variables affecting thiamin nutrition controlled for. Folate, thiamin, and polyphenol intakes were measured during a 4-wk baseline (elderly and young) and 6-wk double-blind (elderly) supplementation period. Only elderly subjects were randomly assigned to placebo, folic acid (400 micrograms), thiamin (10 mg), or folic-acid-plus-thiamin groups. Thiamin status (TPP effect) was not affected by folate status (plasma and erythrocyte folate) during the baseline period or with folic acid supplementation alone. Polyphenol intake was not correlated with thiamin status. Only thiamin intake and thiamin supplementation significantly affected thiamin status. Because the majority of subjects (102 of 160) were initially thiamin deficient, enrichment of Irish grain products with thiamin is recommended.

Adult↗
PubMed2003

Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects.

BACKGROUND: Proanthocyanidins, the most abundant polyphenols in chocolate, are not depolymerized in the stomach and reach the small intestine intact, where they are hardly absorbed because of their high molecular weight. In vitro and in vivo studies using pure compounds as substrates suggest that proanthocyanidins and the related catechin monomers may be degraded into more bioavailable low-molecular-weight phenolic acids by the microflora in the colon. OBJECTIVE: The aim of the study was to estimate the amounts of phenolic acids formed by the microflora and excreted in the urine of human subjects after consumption of polyphenol-rich chocolate. DESIGN: After consumption of a polyphenol-free diet for 2 d and a subsequent overnight fast, 11 healthy subjects (7 men and 4 women) consumed 80 g chocolate containing 439 mg proanthocyanidins and 147 mg catechin monomers. All urine was collected during the 24 h before chocolate consumption and at 3, 6, 9, 24, and 48 h after chocolate consumption. Aromatic acids were identified in urine by gas chromatography-mass spectrometry and were quantified by HPLC-electrospray ionization tandem mass spectrometry. RESULTS: Chocolate intake increased the urinary excretion of the 6 following phenolic acids: m-hydroxyphenylpropionic acid, ferulic acid, 3,4-dihydroxyphenylacetic acid, m-hydroxyphenylacetic acid, vanillic acid, and m-hydroxybenzoic acid. CONCLUSION: The antioxidant and biological effects of chocolate may be explained not solely by the established absorption of catechin monomers but also by the absorption of microbial phenolic acid metabolites.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2005

Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies.

For some classes of dietary polyphenols, there are now sufficient intervention studies to indicate the type and magnitude of effects among humans in vivo, on the basis of short-term changes in biomarkers. Isoflavones (genistein and daidzein, found in soy) have significant effects on bone health among postmenopausal women, together with some weak hormonal effects. Monomeric catechins (found at especially high concentrations in tea) have effects on plasma antioxidant biomarkers and energy metabolism. Procyanidins (oligomeric catechins found at high concentrations in red wine, grapes, cocoa, cranberries, apples, and some supplements such as Pycnogenol) have pronounced effects on the vascular system, including but not limited to plasma antioxidant activity. Quercetin (the main representative of the flavonol class, found at high concentrations in onions, apples, red wine, broccoli, tea, and Ginkgo biloba) influences some carcinogenesis markers and has small effects on plasma antioxidant biomarkers in vivo, although some studies failed to find this effect. Compared with the effects of polyphenols in vitro, the effects in vivo, although significant, are more limited. The reasons for this are 1) lack of validated in vivo biomarkers, especially in the area of carcinogenesis; 2) lack of long-term studies; and 3) lack of understanding or consideration of bioavailability in the in vitro studies, which are subsequently used for the design of in vivo experiments. It is time to rethink the design of in vitro and in vivo studies, so that these issues are carefully considered. The length of human intervention studies should be increased, to more closely reflect the long-term dietary consumption of polyphenols.

Adult↗
PubMed2005

Proposed criteria for assessing the efficacy of cancer reduction by plant foods enriched in carotenoids, glucosinolates, polyphenols and selenocompounds.

BACKGROUND AND AIMS: The cancer-protective properties of vegetable consumption are most likely mediated through 'bioactive compounds' that induce a variety of physiologic functions including acting as direct or indirect antioxidants, regulating enzymes and controlling apoptosis and the cell cycle. The 'functional food' industry has produced and marketed foods enriched with bioactive compounds, but there are no universally accepted criteria for judging efficacy of the compounds or enriched foods. SCOPE: Carotenoids, glucosinolates, polyphenols and selenocompounds are families of bioactive compounds common to vegetables. Although numerous studies have investigated the agricultural and human health implications of enriching foods with one or more of these compounds, inadequate chemical identification of compounds, lack of relevant endpoints and inconsistencies in mechanistic hypotheses and experimental methodologies leave many critical gaps in our understanding of the benefits of such compounds. This review proposes a decision-making process for determining whether there is reasonable evidence of efficacy for the both the compound and the enriched food. These criteria have been used to judge the evidence of efficacy for cancer prevention by carotenoids, polyphenols, glucosinolates and selenocompounds. CONCLUSIONS: The evidence of efficacy is weak for carotenoids and polyphenols; the evidence is stronger for glucosinolates and lycopene, but production of enriched foods still is premature. Additionally there is unacceptable variability in the amount and chemical form of these compounds in plants. The evidence of efficacy for selenocompounds is strong, but the clinical study that is potentially the most convincing is still in progress; also the variability in amount and chemical form of Se in plants is a problem. These gaps in understanding bioactive compounds and their health benefits should not serve to reduce research interest but should, instead, encourage plant and nutritional scientists to work together to develop strategies for improvement of health through food.

Animals↗
PubMed1997

Inhibition of phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate-caused inflammatory responses in SENCAR mouse skin by black tea polyphenols.

Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical tumor promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin-1 alpha (IL-1alpha) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theaflavine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1alpha mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against tumorigenesis. The results of this study suggest that black tea, specifically polyphenols present therein, may be useful against cutaneous inflammatory responses in human population.

Animals↗
PubMed2002

Black tea polyphenols inhibit IGF-I-induced signaling through Akt in normal prostate epithelial cells and Du145 prostate carcinoma cells.

Tea polyphenols have been proposed as potential chemopreventive agents against prostate cancer, primarily because of their high intake by populations with reduced cancer incidence and their reported ability to inhibit proliferation and increase apoptosis in prostate cancer cells in culture. Insulin-like growth factor-I (IGF-I) has been implicated as a risk factor for the development of prostate cancer by epidemiological studies and has been shown to be causative in animal models. One of the primary signal transduction pathways activated by IGF-I binding to its receptor is the Akt pathway. We determined that phosphorylated Akt levels are very low in serum-starved human normal prostate epithelial cells (PrEC) and Du145 prostate carcinoma cells, and that treatment of these cells with IGF-I results in a rapid and sustained phosphorylation of Akt. Pre-treatment of PrEC and Du145 cells with doses as low as 20 microg/ml of a mixture of black tea polyphenols (BTP) substantially reduced IGF-I-mediated Akt phosphorylation. This effect of BTP appears to be due partially to the reduced autophosphorylation of IGF-I receptor-1 in BTP-treated cells. BTP pre-treatment also decreased downstream effects of Akt activation including phosphorylation of glycerol synthase kinase-3, increased cyclin D1 protein levels and increased DNA synthesis. Our results indicate that polyphenols from black tea inhibit the IGF-I signal transduction pathway, which has been linked to increased prostate cancer incidence in human populations and, therefore, provide further support for the potential of BTP to prevent prostate cancer.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1990

Effects of foods rich in polyphenols on nitrogen excretion in rats.

The extent to which tea, cocoa and carob (foods rich in polyphenols) influence fecal nitrogen (N) excretion was investigated in rats. The studies took into account the methylxanthine contents of tea and cocoa as well as the poor digestibility of cocoa nitrogen. Balance measurements indicated that all three food sources significantly increased fecal nitrogen excretion relative to methylxanthine-matched control diets (p less than 0.01). In the case of cocoa, virtually all the increase could be attributed to the poor digestibility of cocoa protein itself (estimated to be only 28-30% of total N in cocoa powder). There appeared to be no other effects. With extracts of tea and carob, however, the increased excretion of N in feces resulted either from a decreased digestibility of other dietary protein, through interaction with their polyphenols, or from a stimulation of the excretion of endogenous (body) nitrogen. With respect to the latter possibility, a preliminary investigation with the stable isotope of nitrogen (15N) showed that tea produced a marked increase in the excretion of endogenous nitrogen. These studies, therefore, indicate that foods rich in polyphenols have varying effects on N excretion in feces and that, in the case of tea at least, the loss of endogenous nitrogen may be a major contributing factor.

Animals↗