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Inhibitory effects of polyphenols in leaves of Artemisia princeps PAMP on protein fragmentation by Cu(II)-H2O2 in vitro.

The leaves of Artemisia princeps PAMP have traditionally been used as teas and foods in Japan. Polyphenols in Artemisia plants have been shown to have inhibitory effects against biological damages. The inhibitory effects of polyphenols in the leaves of A. princeps PAMP were investigated on protein fragmentation induced by Cu(II)-H(2)O(2) in vitro. The total polyphenol content in the leaves of A. princeps PAMP was 4.58%. The condensed tannin content was 0.62% by vanillin assay and 0.14% by proanthrocyanidin assay. The polyphenols in the leaves of A. princeps PAMP inhibited bovine albumin fragmentation by Cu(II)-H(2)O(2). The effects of polyphenols in the leaves of A. princeps PAMP were similar to those of tannic acid, studied as a related polyphenol. These results demonstrated that the leaves of A. princeps PAMP have inhibitory effects on protein fragmentation damage.

Antioxidants↗

Polyphenols: antioxidants and beyond.

Research on the effects of dietary polyphenols on human health has developed considerably in the past 10 y. It strongly supports a role for polyphenols in the prevention of degenerative diseases, particularly cardiovascular diseases and cancers. The antioxidant properties of polyphenols have been widely studied, but it has become clear that the mechanisms of action of polyphenols go beyond the modulation of oxidative stress. This supplemental issue of The American Journal of Clinical Nutrition, published on the occasion of the 1st International Conference on Polyphenols and Health, offers an overview of the experimental, clinical, and epidemiologic evidence of the effects of polyphenols on health.

Animals↗

Suppression of extracellular signals and cell proliferation by the black tea polyphenol, theaflavin-3,3'-digallate.

Previous studies in our laboratory have shown that the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), suppressed autophosphorylation of epidermal growth factor (EGF) receptor induced by EGF in human A431 epidermoid carcinoma cells. In this study, we examined the inhibitory effects of black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate (TF-2a) and theaflavin-3'-gallate (TF-2b), theaflavin-3,3'-digallate (TF-3) and the thearubigin fraction on the autophosphorylation of the EGF and PDGF receptors in A431 cells and mouse NIH3T3 fibroblast cells, respectively. First, we examined the effects of these polyphenols on the proliferation of A431 and NIH3T3 cells. Both EGCG and TF-3 strongly inhibited the proliferation of A431 and NIH3T3 cells more than the other theaflavins did. In cultured cells with pre-treatment of tea polyphenol, TF-3 was stronger than EGCG on the reduction of EGF receptor and PDGF receptor autophosphorylation induced by EGF and PDGF, respectively. Other theaflavins slightly reduced the autophosphorylation of the EGF and PDGF receptors; furthermore, TF-3 could reduce autophosphorylation of the EGF receptor (or PDGF receptor) even with co-treatment with EGF (or PDGF) and TF-3, but EGCG was inactive under these conditions. In addition, TF-3 was stronger than EGCG in blocking EGF binding to its receptor. These results suggest that not only the green tea polyphenol, EGCG, but also the black tea polyphenol, TF-3, have an antiproliferative activity on tumor cells, and the molecular mechanisms of antiproliferation may block the growth factor binding to its receptor and thus suppress mitogenic signal transduction.

3T3 Cells↗

Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China.

Experimental studies have shown that tea and tea polyphenols have anticarcinogenic properties. There have been no prospective investigations examining the relationship between tea polyphenols and cancer risk using validated biomarkers. In the present study, a nested case-control study design was used to investigate the association between prediagnostic urinary tea polyphenol markers and subsequent risk of gastric and esophageal cancers. One hundred and ninety incident cases of gastric cancer and 42 cases of esophageal cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years at recruitment with up to 12 years of follow-up) were compared with 772 cohort control subjects. The control subjects were individually matched to the index cases by age, month and year of sample collection, and neighborhood of residence (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models. After exclusion of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a statistically significant inverse association with gastric cancer (OR = 0.52, 95% CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking, alcohol drinking, and level of serum carotenes. The protective effect was primarily seen among subjects with low (below population median) serum carotenes. The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects with low serum carotenes while the corresponding odds ratio among subjects with higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea polyphenol-cancer risk associations were observed when the gastric cancer and esophageal cancer sites were combined. The present study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development.

Adult↗

Lipoprotein oxidation mediated by J774 murine macrophages is inhibited by individual red wine polyphenols but not by ethanol.

The in vitro capacities of individual polyphenols in red wine to inhibit the cell-mediated oxidation of lipoproteins and their effects on cell viability were determined. LDL and HDL were incubated with J774.A1 macrophages and 2 and 4 micro mol/L copper, respectively, in the absence and presence of polyphenols in ethanol at concentrations found in red wine. A mixture of polyphenols in amounts found in red wine equivalent to 0.2 g/L ethanol and 0.05 g/L ethanol inhibited thiobarbituric acid-reactive substance production from LDL by 91.7 and 45.9%, respectively, compared with ethanol controls (P < 0.01). HDL oxidation was inhibited 85 and 82.4% by the polyphenols at 0.2 and 0.05 g/L ethanol (P < 0.01). The effects of the polyphenol mixture on LDL oxidation were confirmed by measuring production of conjugated dienes and lipid peroxides, and trinitrobenzene sulfonic acid reactivity. Catechin at the concentration found in red wine (1.32 micro mol/L) at an ethanol concentration equivalent to 0.2 g/L inhibited LDL oxidation by 83.2%, while epicatechin (0.56 micro mol/L) and gallic acid (1.02 micro mol/L) inhibited by 60.6 and 26.9%, respectively (P < 0.05). At 1 micro mol/L, LDL oxidation was inhibited by epicatechin, catechin and quercetin by 86.2, 79.9 and 69.4%, respectively (P < 0.05). Incubation of macrophages with ethanol alone and with polyphenols in ethanol did not affect cell viability. Our results indicate that catechin and epicatechin are the major contributors to the antioxidant activity of red wine.

Adult↗

Polyphenols and gastrointestinal diseases.

PURPOSE OF REVIEW: This article will review the role of polyphenols in gastrointestinal diseases. Ingested polyphenols are concentrated in the gastrointestinal tract and are not well absorbed into the rest of the body. Thus, the high luminal concentrations achieved support a potential for therapeutic uses in the gastrointestinal tract. Additionally, there is great interest from the general public in complementary and alternative medicine. RECENT FINDINGS: Dietary polyphenols are a major source of antioxidants consumed by humans. Polyphenols possess not only antioxidant properties but also antiviral, antibacterial, antiinflammatory and anticarcinogenic effects, as well as the ability to modulate certain signaling pathways such as nuclear factor-kappaB activation. Green tea polyphenols have been shown to have efficacy in various models of inflammatory bowel disease. Silymarin, or milk thistle, is hepatoprotective against many forms of experimental liver injury and is widely used in human liver diseases, such as hepatitis C and alcoholic cirrhosis, with an excellent safety profile (but with unclear efficacy). SUMMARY: Substantial in-vitro and animal studies support the beneficial effects of polyphenols in many gastrointestinal diseases. Well designed multicenter trials in humans, such as those called for in the 2005 National Institutes of Health Requests for Applications for Silymarin Centers, will be critical for defining the safety, appropriate dosing and therapeutic efficacy of such agents.

Animals↗

Tea polyphenol intake and changes in serum pepsinogen levels.

Following a phase I study, a phase II study was conducted to evaluate the effects of two different doses of tea polyphenols on serum pepsinogen levels. Subjects were patients aged 40 to 69 years who had undergone gastroscopy between 1995 and 1997 at Aichi Cancer Center Hospital, and had been found to have no disease requiring medication. Those with pepsinogen I < 70 ng/ml and pepsinogen I/II ratio < 6 were included in this study. Capsules containing 100 mg of tea polyphenols were administered for 1 year: 1 capsule per day for 101 patients (42 males and 59 females), and 6 capsules (equivalent to 10 cups) per day for 83 patients (30 males and 53 females). The enrollment of the 1 capsule group preceded that of the 6 capsule group, in which re-participation was allowed. Blood samples were obtained 1 year after participation from 86 participants of the 1 capsule group and 77 participants (43 new participants and 34 re-participants) of the 6 capsule group. The compliance in polyphenol capsule intake ranged from 11.4 to 105.7% (87.6% on average) of the scheduled amount for the 1 capsule group and 3.2 to 112.3% (77.8% on average) for the 6 capsule group. No serious polyphenol-related adverse effects were reported. The difference in pepsinogen I between before and after 1 year intake of the polyphenol was 3.1 ng/ml for the 43 participants of the 6 capsule group, but 3.5 ng/ml for the 1 capsule group. The mean pepsinogen I/II ratio for the 43 participants increased from 2.37 by 0.08. This increase was not larger than that for the 1 capsule group (from 2.61 by 0.11). Among 34 participants in both interventions, no significant increase in pepsinogen I and I/II ratio for the 6 capsule intervention was observed. This result suggests that additional polyphenol intake for 1 year in Japanese does not improve pepsinogen levels, which are considered to reflect stomach atrophy, a high-risk condition for stomach cancer.

Adult↗

Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans.

The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects.

Aging↗

The effect of cocoa polyphenols on the growth, metabolism, and biofilm formation by Streptococcus mutans and Streptococcus sanguinis.

The aim of this study was to determine if cocoa polyphenols could interfere with biofilm formation by Streptococcus mutans or Streptococcus sanguinis, and reduce acid production from sucrose by S. mutans. The antimicrobial activity of cocoa polyphenols was assessed against cariogenic (S. mutans) and health-associated (S. sanguinis) species by minimum inhibitory concentration assays. Cocoa polyphenol dimer, tetramer, and pentamer inhibited the growth of S. sanguinis, whereas the growth of S. mutans was unaffected. However, pretreatment of surfaces with cocoa polyphenol pentamer (35 microM) reduced biofilm formation by S. mutans at 4 and 24 h, whereas the effects on S. sanguinis were less consistent. In contrast, brief exposure of preformed biofilms to pentamer either had no significant effect or resulted in increased counts of S. mutans under certain conditions. Cocoa polyphenol pentamer (500 microM) significantly reduced the terminal pH, and inhibited the rate of acid production by S. mutans at pH 7.0. In conclusion, cocoa polyphenols can reduce biofilm formation by S. mutans and S. sanguinis, and inhibit acid production by S. mutans.

Acids↗

p38 mitogen-activated protein kinase activates eNOS in endothelial cells by an estrogen receptor alpha-dependent pathway in response to black tea polyphenols.

Black tea has been shown to improve endothelial function in patients with coronary artery disease and recent data indicate the polyphenol fraction of black tea enhances endothelial nitric oxide synthase (eNOS) activity through p38 MAP kinase (p38 MAPK) activation. Because the mechanisms for this phenomenon are not yet clear, we sought to elucidate the signaling events in response to black tea polyphenols. Bovine aortic endothelial cells (BAECs) exposed to black tea polyphenols demonstrated eNOS activation that was inhibited by the estrogen receptor (ER) antagonist ICI 182,780, and siRNA-mediated silencing of ER expression. Consistent with this observation, black tea polyphenols induced time-dependent phosphorylation of ERalpha on Ser-118 that was inhibited by ICI 182,780. Phosphorylation of ERalpha on Ser-118 was due to p38 MAP kinase (p38 MAPK) as, it was inhibited by SB203580 and overexpression of dominant-negative p38alpha MAPK. Conversely, constitutively active MKK6 induced p38 MAPK activation that recapitulated the effects of polyphenols by inducing ERalpha phosphorylation and downstream activation of Akt, and eNOS. The key role of ERalpha Ser-118 phosphorylation was confirmed in eNOS-transfected COS-7 cells, as polyphenol-induced eNOS activation required cotransfection with ERalpha subject to phosphorylation at Ser-118. This residue appeared critical for functional association of ERalpha with p38 MAPK as ERalpha with Ser-118 mutated to alanine could not form a complex with p38 MAPK. These findings suggest p38 MAP kinase-mediated eNOS activation requires ERalpha and these data uncover a new mechanism of ERalpha activation that has broad implications for NO bioactivity and endothelial cell phenotype.

Animals↗

A new method of measuring the antioxidant activity of polyphenols using cumene hydroperoxide.

BACKGROUND: It is well known that polyphenols lower the risk of chronic diseases such as heart disease and cancer. We describe a new method using cumene hydroperoxide (CHP) to determine the antioxidant activity of polyphenols. CHP is considered to be a model reactive lipid peroxidation product. METHODS: The method was based on two reactions: the reduction of a known concentration of CHP by polyphenols and the reaction of the remaining CHP with a methylene blue derivative (10-N-methylcarbamoyl-3,7 dimethylamino-10H-phenothiazine) in the presence of haemoglobin. Methylene blue was formed as a result of the two reactions and then measured by absorbance at 675 nm. We named this assay the 'cumene hydroperoxide/haemoglobin.methylene blue (CHP/Hb.MB) method'. We examined 13 polyphenols and nine compounds known to be antioxidants. RESULTS: Among the 13 polyphenols, milicetin, with the largest number of hydroxyl groups, had the highest antioxidant activity, followed by cyanidin, pelargonidin and quercetin. It is suggested that the increase in the number of hydroxyl groups induced a higher antioxidant activity. Within-run coefficients of variation were 3.6% and 3.5% at the mean antioxidant activity of 50 micromol/L and 151 micromol/L, respectively. CONCLUSION: We conclude that this CHP/Hb.MB assay is capable of measuring the antioxidant activity of polyphenols.

Antioxidants↗

[Induction of apoptosis by tea polyphenols in MGC cells].

In order to search for tumor cells apoptosis inducer, the apoptosis effects and mechanism of tea polyphenols were studied. Tea polyphenols is an active compounds purified from tea. The apoptosis effects of tea polyphenols were observed on the human gastric carcinoma cells (MGC) by MTT reduction test, DNA agarose gel electrophoresis and transmission electron microscopy (TEM) technique. Having been treated by tea polyphenols in 125 micrograms.ml-1 for 24 h, DNA extracted from MGC cells showed a typical internuclesosomal DNA degradation, i.e., DNA ladder and apoptotic vehicles were observed under TEM. The effects of tea polyphenols were shown to parallel with its cytotoxic activity in MGC cells. These results suggest that the mechanism of antitumor action of tea polyphenols is related to its apoptosis inducing activity.

Adenocarcinoma↗

[Variability of polyphenol content in different types of wine and its potential application in the understanding of its biologic effects].

BACKGROUND: Wine polyphenols have antioxidant properties. Different polyphenols have various biological activities on atherogenesis and carcinogenesis. MATERIAL AND METHODS: The composition on 5 polyphenols of 16 wines of Castilla (Spain) is determined by HPLC. RESULTS: Polyphenols concentrations varied largely among the different wines. Most red wines had higher amounts of polyphenols than white wines. CONCLUSIONS: The diverse composition on polyphenols of each wine allows to suggest different biological effects.

Flavonoids↗

Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies.

Epidemiological studies suggest that tea drinking may reduce the risk of cardiovascular diseases and cancers. Although tea is an important source of antioxidant phytochemicals, variation in preparation techniques may translate to variation in antioxidant capacity. However, most large-scale epidemiological studies use regular food frequency questionnaires to estimate tea intake, and nationally available nutrient analysis databases do not include levels of black tea polyphenols. The Arizona Tea Questionnaire (ATQ) was designed as a tool for collecting more complete dietary tea consumption information, and a database was developed after analyzing 40 black tea samples (brewed, instant, and sun tea) for polyphenols. This study assesses the reliability and relative validity of the ATQ and polyphenol database. Relative validity of estimates of black tea consumption was tested by comparing the ATQ with the traditional Arizona Food Frequency Questionnaire and four days of food records. The ATQ was tested for reproducibility of estimates of black (hot and iced) tea consumption and levels of black tea polyphenol intake. Correlations between two measures of intake taken 2 months apart ranged from 0.72 for black hot tea to 0.86 for black sun tea. Mean intakes (range) of total flavonoids for black tea consumers were 80.8 (3.0-588.0) mg/day at the first ATQ and 102.4 (4.5-802.3) mg/day at the second ATQ (r = 0.83, P < 0.001). The ATQ provided highly reproducible estimates of both total tea consumption and individual tea polyphenol intake. This instrument may be a useful tool in studies of the associations between tea consumption, tea polyphenols intake, and risk for chronic disease.

Adult↗

[Experimental study on polyphenol anti-plaque effect in human].

OBJECTIVE: To evaluate anti-caries effect of Chinese green tea's polyphenol. METHODS: 150 volunteers are randomly divided into 3 groups: A, B test group and contrast group, 50 persons in each. People in test groups were given polyphenol's tablet, placebo was given in contrast group, a tablet three times a day. After 3 weeks, group A was given placebo and group B continued polyphenol for 6 weeks. RESULTS: After using polyphenol's tablet for 2 weeks, the plaque index of test groups were evidently lower than the contrast group (P < 0.01). After stopping use of polyphenol tablet, the effect was still kept for 3 weeks. CONCLUSION: It can be concluded that polyphenol tablet from Chinese green tea has evident anti-plaque effect.

Child↗

[Polyphenols and anthocyanins in fruits, grapes juices and wines, and evaluation of their antioxidant activity].

The objective of this study was to produce grape (Vitis vinifera L.) extracts using efficient solvents and to compare antioxidant activity, polyphenol and anthocyanin content and composition in the produced extracts to the same characteristics of grape juices and wines. Methanolic and aqueous extracts of red and blue grapes were produced. Total amounts of polyphenols and anthocyanins in grape extracts, juices and wines were determined. Total polyphenols were spectrophotometrically determined measuring absorption after using Folin-Ciocalteau reagent. Total anthocyanins were determined by pH-differential method. Antioxidant activity of all those grape products was analyzed in 2,2-diphenyl-1-picrylhydrazil (DPPH) and 2,2'-azine-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radical binding model systems. The results obtained by both antioxidant activity determination methods were comparable and permitted to evaluate the ability to inactivate free radicals. Individual polyphenols and anthocyanins were separated by high performance liquid chromatography. Compounds of malvidine, delphinidine and petunidine were identified as main anthocyanins present in grape products demonstrating antioxidant activity. The determined amounts of polyphenols and anthocyanins in red wines were relatively higher than in other investigated objects. The wines possessed the highest antioxidant activity, which correlated with the determined amounts of total polyphenols. Correlation between total anthocyanins contents and antioxidant activity of appropriate objects was not established.

Anthocyanins↗

[Application of plant polyphenols in environmental protection and agricultural production].

Plant polyphenols, the secondary metabolites in plant, contain many phenol-hydroxyl groups. They can bind with protein, alkaloids and polysaccharides, and consequently, exhibit an astringent property. Plant polyphenols can also bind with metal ions to form polyphenol-metal complexes, which are probably soluble or precipitated, depending on the type of plant polyphenols. Up to now, about 600 plant polyphenols have been found. Plant polyphenols can be applied widely in environmental pollution control and agriculture production.

Crops, Agricultural↗

[Effects of tea polyphenols on cell proliferation and hTERT of human Tca8113 cell lines].

OBJECTIVE: To investigate the effects of tea polyphenols (TP) on cell proliferation and human telomerase reverse transcriptase (hTERT). METHODS: The experiment was divided into tea polyphenols 0.100 g/L, tea polyphenols 0.050 g/L and blank control groups. The inhibitory ratio of cell proliferation was assayed with MTT, and hTERT mRNA was detected by RT-PCR, and hTERT protein analyzed by Western-blotting. The data were analyzed by one-way ANOVA and Student-Newman-Keuls of SPSS 11.0 for windows. RESULTS: Cell proliferations were significantly inhibited after exposure to TP. The proliferation inhibiting rate of TP 0.025, 0.050, 0.100, 0.200 g/L on Tca8113 cell at 72 h was 69.75% +/- 3.24%, 63.17% +/- 3.19%, 50.35% +/- 4.21% and 34.75% +/- 3.71%, respectively (F = 270.19, P < 0.05). At the end of 72 h, the hTERT mRNA expression in TP 0.100 g/L, 0.050 g/L and control group were 0.32 +/- 0.05, 0.41 +/- 0.04, 0.72 +/- 0.05, respectively (P < 0.05). The Western-blotting assay showed that hTERT protein was also decreased by tea polyphenols compared to control group. CONCLUSIONS: Tea polyphenols could inhibit the proliferation of Tca8113 cells and expression of the hTERT mRNA and protein in Tca8113 cell lines. This effect might be one of the mechanisms for anticancer function of tea polyphenols.

Carcinoma, Squamous Cell↗