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PubMed2000

Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines.

The effect of different wine antioxidant polyphenols (catechin, epicatechin, quercetin, and resveratrol) on the growth of three prostate cancer cell lines (LNCaP, PC3, and DU145) was investigated. A dose- and time-dependent inhibition of cell growth by polyphenols was found at nanomolar concentrations. The proliferation of LNCaP and PC3 cells was preferentially inhibited by flavonoids (catechin, epicatechin, and quercetin), whereas resveratrol was the most potent inhibitor of DU145 cell growth. Possible mechanisms of action were investigated: 1) The competition of polyphenols for androgen binding in LNCaP cells revealed significant interaction only in the case of high concentrations of quercetin, at least at five orders of magnitude higher than the concentrations needed for cell growth inhibition. All other phenols showed low interactions. 2) Oxygen species production after mitogen stimulation and H2O2 sensitivity of these cell lines did not correlate with the observed antiproliferative effects, ruling out such a mode of action. 3) NO production revealed two different patterns: LNCaP and DU145 cells produced high concentrations of NO, whereas PC3 cells produced low concentrations. Phorbol ester stimulation of cells did not reveal any additional effect in LNCaP and DU145 cells, whereas it enhanced the secretion of NO in PC3 cells. Polyphenols decreased NO secretion. This effect correlates with their antiproliferative action and the inhibition of inducible NO synthase. It is therefore proposed that the antiproliferative effect of polyphenols is mediated through the modulation of NO production. In conclusion, our data show a direct inhibitory effect of low concentrations of antioxidant wine phenols on the proliferation of human prostate cancer cell lines mediated by the production of NO, further suggesting potential beneficial effects of wine and other phenol-containing foods or drinks for the control of prostate cancer cell growth.

Antioxidants↗
PubMed2000

Effect of tea polyphenols and tea pigments on the inhibition of precancerous liver lesions in rats.

The objective of this study was to investigate the inhibitory effect of tea components, tea polyphenols and tea pigments, on precancerous liver lesions in rats. A rat liver precancerous lesion model was established by multiple low-dosage N-nitrosodiethylamine (NDEA) injections, followed by intraperitoneal CCl4 injection and partial hepatectomy (PH). Tea pigments (0.1%) or tea polyphenols (0.1%) were given to Wistar rats in drinking water during the eight weeks of the experiment. The number and area of glutathione S-transferase Pi-positive foci in the rat liver were used as biomarkers of precancerous liver lesions. Western and Northern blot techniques were used to detect rat liver GST-Pi expression at the protein and mRNA levels. At the end of the experiment, tea polyphenols and tea pigments significantly decreased the number and area of GST-Pi-positive foci that were overexpressed in the NDEA-CCl4-PH-treated rats compared with the positive control group. The results also showed that GST-Pi mRNA and protein expression increased significantly in the NDEA-CCl4-PH-treated group, which is consistent with the changing of GST-Pi-positive foci. Tea pigments and tea polyphenols had an inhibitory effect on the overexpression of GST-Pi mRNA and protein in NDEA-CCl4-PH-treated rats. These results suggest that tea pigments and tea polyphenols are effective in preventing the occurrence and progression of precancerous liver lesions in rats.

Animals↗
PubMed2006

The inhibition of paw oedema formation caused by the oil of Copaifera multijuga Hayne and its fractions.

Two oils exuded from a Copaifera multijuga Hayne tree (Leguminosae-Caesalpinoideae), collected from the same plant, but in different periods of the year, and the hexanic, dichloromethanic and methanolic fractions of one of these oils were analysed by high-resolution gas chromatography (HRGC) and HRGC coupled with mass spectrometry (HRGC-MS). In addition, the in-vivo preliminary anti-oedematogenic actions of the oil and some fractions of it were assessed against carrageenan- and bradykinin-induced oedema formation in the rat paw. Twenty-seven sesquiterpenes and six diterpenes were identified, beta-caryophyllene, alpha-copaene and copalic acid being the main components. The dichloromethanic and methanolic fractions obtained from C. multijuga oil given by the intraperitoneal route caused a significant inhibition of paw oedema caused by carrageenan with inhibition of 49 +/- 13% and 64 +/- 9 %, respectively. Likewise, dexamethasone (the positive control drug) also greatly inhibited carrageenan-induced paw oedema formation (60 +/- 4% at 2 h). The hexanic fraction also significantly inhibited (50 +/- 6%) the paw oedema formation caused by bradykinin. These results suggest the presence of still non-identified active terpene compounds in the oil of C. multijuga that exhibit anti-oedematogenic properties. Of note, the yield of these compounds and the pharmacological actions of the oil, exhibited great seasonal variations, a relevant aspect that should be carefully observed for the correct medicinal use of this plant by the population.

Animals↗
PubMed2003

Tea polyphenols regulate nicotinamide adenine dinucleotide phosphate oxidase subunit expression and ameliorate angiotensin II-induced hyperpermeability in endothelial cells.

Out-of-control reactive oxygen species (ROS) signaling is one of the key events in the pathogenesis of endothelial dysfunction and essential hypertension. We observed that tea polyphenols decreased the production of ROS via regulation of the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in bovine carotid artery endothelial cells (BCAECs). Both green tea polyphenols (GTP) and black tea polyphenols (BTP) down-regulated the expression of NADPH oxidase subunits p22phox and p67phox while up-regulating catalase expression (p < 0.05, respectively). Pre-treatment with GTP or BTP for 24 h significantly decreased the superoxide anion level (p < 0.05) and permeable fluorescence intensities in Ang II-stimulated BCAECs. A decrease in cell permeability was also observed by pre-treatment with diphenylene iodonium chloride (DPI) or vitamin E (p < 0.05, respectively). The result demonstrates that tea polyphenols alleviate angiotensin (Ang) II-induced hyperpermeability mainly by decreasing ROS production. Our results suggest that tea polyphenols regulate ROS-related protein expression and may be beneficial in preventing endothelial cell dysfunction and development of cardiovascular diseases, including hypertension.

Angiotensin II↗
PubMed2000

Effects of acute and chronic coingestion of AlCl3 with citrate or polyphenolic acids on tissue retention and distribution of aluminum in rats.

Aluminum (Al) is toxic to certain biological systems and has been implicated as a neurotoxic agent in the pathogenesis of Alzheimer's disease. Intestinal absorption of Al is very low (0.1%), but many organic dietary components are potential chelators of Al and may enhance its absorption and tissue distribution. We examined the effects of acute and chronic coingestion of AlCl3 with different polyphenolic acids on Al retention and compared to citrate in rats. In experiment 1, animals fasted for 14 h were dosed orally with demineralized water, Al chloride, Al chloride plus sodium citrate, or Al chloride plus a polyphenol acid. Blood samples were taken before and 2 h after the gavage and animals were killed 6 h later. In experiment 2, the rats were adapted on a purified diet for 1 wk and received the following for 4 wk in their experimental diets: AlCl3, except group 1, plus citrate or a polyphenol acid, except groups 1 and 2. Animals were killed and blood and tissues were sampled. In experiment 1, citrate highly enhanced Al absorption and its tissue retention. Gallic and chlorogenic acids significantly increased tibia and kidney Al levels compared to the Al group. In experiment 2, Al levels in the urine were significantly increased in all the Al groups compared to the control group. Significantly higher Al levels in the tibia, kidney, and brain were observed in the citrate group and a significant increase in brain Al level was also noted in the chlorogenic acid group compared to AlCl3 group. This may suggest a possible relation structure-activity of polyphenol acids. However, further studies are necessary to better understand the influence of polyphenol acids on Al metabolism, in particular that of chlorogenic acid.

Aluminum↗
PubMed2005

Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis.

BACKGROUND: Enamel matrix derivative (EMD) is a tissue regenerative agent used clinically as an adjunct to periodontal surgery. It was previously demonstrated that Porphyromonas gingivalis, a periodontal pathogen, significantly diminished the efficacy of EMD with periodontal ligament (PDL) cells through the proteolytic actions of Arg- and Lys-gingipains (Rgp and Kgp). Thus, antiproteolytic supplements are considered clinically desirable for effective periodontal regenerative therapies. In the present study, we examined apple- (AP) and hop-polyphenols to determine their ability to protect EMD-stimulated PDL cells from P. gingivalis. METHODS: AP, apple condensed tannin (ACT), hop bract polyphenol (HBP), high and low molecular weight fractions of HBP (HMW-HBP and LMW-HBP), and epigallocatechin gallate (EGCg) were used. PDL cells were grown on EMD-coated dishes and infected with P. gingivalis, and cellular migration and proliferation were evaluated with an in vitro assay of wound healing assay in the presence or absence of the polyphenols. RESULTS: Each polyphenol significantly enhanced the viability of PDL cells infected with P. gingivalis, whereas only EGCg demonstrated cytotoxicity. Further, all polyphenols significantly inhibited Rgp activity, with AP, ACT, and HBP more effective toward Kgp. P. gingivalis markedly diminished the migration and proliferation of EMD-stimulated PDL cells, whereas the addition of AP, ACT, HBP, and HMW-HBP significantly protected the cells from bacterial cytotoxicity. In contrast, EGCg and LMW-HBP did not show protective effects. CONCLUSION: These results suggest that AP, ACT, AP, HBP, and HMW-HBP protect EMD-stimulated PDL cells from P. gingivalis and may be therapeutically useful supplements for EMD therapy.

Adhesins, Bacterial↗
PubMed2003

Potential therapeutic properties of green tea polyphenols in Parkinson's disease.

Tea is one of the most frequently consumed beverages in the world. It is rich in polyphenols, a group of compounds that exhibit numerous biochemical activities. Green tea is not fermented and contains more catechins than black tea or oolong tea. Although clinical evidence is still limited, the circumstantial data from several recent studies suggest that green tea polyphenols may promote health and reduce disease occurrence, and possibly protect against Parkinson's disease and other neurodegenerative diseases. Green tea polyphenols have demonstrated neuroprotectant activity in cell cultures and animal models, such as the prevention of neurotoxin-induced cell injury. The biological properties of green tea polyphenols reported in the literature include antioxidant actions, free radical scavenging, iron-chelating properties, (3)H-dopamine and (3)H-methyl-4-phenylpyridine uptake inhibition, catechol-O-methyltransferase activity reduction, protein kinase C or extracellular signal-regulated kinases signal pathway activation, and cell survival/cell cycle gene modulation. All of these biological effects may benefit patients with Parkinson's disease. Despite numerous studies in recent years, the understanding of the biological activities and health benefits of green tea polyphenols is still very limited. Further in-depth studies are needed to investigate the safety and efficacy of green tea in humans and to determine the different mechanisms of green tea in neuroprotection.

Animals↗
PubMed2006

Mechanisms of cancer prevention by green and black tea polyphenols.

Drinking green tea is associated with decreased frequency of cancer development. This review outlines the wide range of mechanisms by which epigallocatechin gallate (ECGC) and other green and black tea polyphenols inhibit cancer cell survival. EGCG suppressed androgen receptor expression and signalling via several growth factor receptors. Cell cycle arrest or apoptosis involved caspase activation and altered Bcl-2 family member expression. EGCG inhibited telomerase activity and led to telomere fragmentation. While at high concentrations polyphenols had pro-oxidative activities, at much lower levels, anti-oxidative effects occurred. Nitric oxide production was reduced by EGCG and black tea theaflavins by suppressing inducible nitric oxide synthase via blocking nuclear translocation of the transcription factor nuclear factor-kappaB as a result of decreased IkappaB kinase activity. Polyphenols up- or down-regulated activity of a number of key enzymes, including mitogen-activated protein kinases and protein kinase C, and increased or decreased protein/mRNA levels, including that of cyclins, oncogenes, and tumor suppressor genes. Metastasis was inhibited via effects on urokinase and matrix metalloproteinases. Polyphenols reduced angiogenesis, in part by decreasing vascular endothelial growth factor production and receptor phosphorylation. Recent work demonstrated that EGCG reduced dihydrofolate reductase activity, which would affect nucleic acid and protein synthesis. It also acted as an aryl hydrocarbon receptor an-tagonist by directly binding the receptor's molecular chaperone, heat shock protein 90. In conclusion, green and black tea polyphenols act at numerous points regulating cancer cell growth, survival, and metastasis, including effects at the DNA, RNA, and protein levels.

Animals↗
PubMed2006

Cellular mechanisms of the protective effect of polyphenols on the neurovascular unit in strokes.

Increasing evidence has suggested that our view of stroke should be integrative, and thus a concept of dynamic interaction between cells belonging to the neurovascular unit, such as endothelial cells, astrocytes and neurons, is emerging. The functionality of this unit is altered by the complex series of interconnected pathophysiological processes that damage the brain tissue during this kind of attack. The new strategies target both the preservation of endothelium integrity and the deleterious effects induced by ionic imbalance, excitotoxicity, and the generation of reactive oxygen species within the neurovascular unit. Polyphenols exert numerous biological effects that might participate in the protection of the neurovascular unit, including anti-aggregatory platelet activity, antioxidant and free radical scavenging properties. Moreover, polyphenols are powerful vasodilators through the generation of NO, and can act on the expression of genes protective of the cardiovascular system. Also, polyphenols contribute to the preservation of the integrity of cells belonging to the neurovascular unit, mainly the endothelium, by acting on the signaling cascades implicated in endothelial apoptosis. All these effects of polyphenols might interfere with atherosclerotic plaque development and stability, vascular thrombosis and occlusion and therefore might explain their vascular- and neuroprotective properties. In this review, we focus on the beneficial effects of polyphenols on the complex pathophysiological events of stroke and helpful indications for the design of an effective and well-tolerated therapy will be discussed.

Animals↗
PubMed1998

Effect of black tea polyphenols on plasma lipids in cholesterol-fed rats.

The influence of black tea polyphenols on plasma lipid levels was investigated in rats fed a 15% lard and 1% cholesterol diet. The diet was supplemented with 1% black tea polyphenols extracted and condensed from black tea. Rats fed the lard-cholesterol diet showed an increase in plasma cholesterol and liver lipids compared to rats fed a basal diet. The supplementation of black tea polyphenols in this lard-cholesterol diet decreased the lipid levels in the plasma and increased the fecal excretion of total lipids and cholesterol. On the other hands, 1% supplementation of either instant black tea with a 20% polyphenol content of 0.2% supplementation of EGCg in the lard-cholesterol diet had no effect on plasma cholesterol and phospholipid levels. These results suggest that a high dose of black tea polyphenols exerts a hypocholesterolemic effect in cholesterol-fed rats.

Animals↗
PubMed2005

Molecular targets of dietary polyphenols with anti-inflammatory properties.

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.

Animals↗
PubMed2005

Red wine polyphenols prevent endothelial damage induced by CCl4 administration.

It became evident in the present study that carbon tetrachloride (CCl(4)), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CC(4)/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 microl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl(4) treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5+/-0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl(4) did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl(4) may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl(4). This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.

Animals↗
PubMed2000

Plant polyphenol antioxidants and oxidative stress.

In recent years there has been a remarkable increment in scientific articles dealing with oxidative stress. Several reasons justify this trend: knowledge about reactive oxygen and nitrogen species metabolism; definition of markers for oxidative damage; evidence linking chronic diseases and oxidative stress; identification of flavonoids and other dietary polyphenol antioxidants present in plant foods as bioactive molecules; and data supporting the idea that health benefits associated with fruits, vegetables and red wine in the diet are probably linked to the polyphenol antioxidants they contain. In this review we examine some of the evidence linking chronic diseases and oxidative stress, the distribution and basic structure of plant polyphenol antioxidants, some biological effects of polyphenols, and data related to their bioavailability and the metabolic changes they undergo in the intestinal lumen and after absorption into the organism. Finally, we consider some of the challenges that research in this area currently faces, with particular emphasis on the contributions made at the International Symposium "Biology and Pathology of Free Radicals: Plant and Wine Polyphenol Antioxidants" held July 29-30, 1999, at the Catholic University, Santiago, Chile and collected in this special issue of Biological Research.

Antioxidants↗
PubMed1998

[Effects of tea polyphenol on blood lipid and antioxidation in vivo in aged rats].

OBJECTIVE: To study the ability of tea polyphenol to lowering blood lipid and antioxidation in the aged rats. METHODS: The SD rats were divided into three groups, i.e., control group and two trial groups fed with 1% and 2% tea polyphenol for six weeks, respectively. RESULTS: Tea polyphenol could reduce serum level of lipid peroxide and increase the ratio of high-density lipoprotein cholesterol (HDL-C) to total cholesterol (TC), and significantly lower serum level of lipid peroxide in rats. Activities of superoxide dismutase in red blood cells of rats fed with 2% tea polyphenol were significantly higher than those in control ones. CONCLUSION: Tea polyphenol can enhance antioxidation in vivo in the aged rats.

Aging↗
PubMed2000

Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics.

Naturally occurring dimeric polyphenolics and their gallate esters were isolated from grape seeds, almond fruits, and apple skin, and their ability to modulate the mutagenicity of food carcinogens was studied in the Ames test, and compared to that of the monomeric green tea flavonols, (+)-catechin and (-)-epicatechin. Neither the monomeric nor the dimeric polyphenols and their galloylated derivatives influenced the mutagenic activity elicited by the indirectly acting food carcinogens benzo[a]pyrene and 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), in the presence of a hepatic activation system derived from Aroclor 1254-treated rats; the only exception was the B7 dimer, which, at concentrations above 1 microM, suppressed the mutagenicity of IQ. None of the polyphenolics modulated the mutagenic activity elicited by the directly acting carcinogen N'-methyl-N'-nitro-nitrosoguanidine (MNNG). In contrast, all the dimeric polyphenols and the galloylated metabolites, at concentrations over 1 microM, potentiated the mutagenic activity induced by the indirectly acting carcinogen N-nitrosopyrrolidine, in the presence of an activation system derived from isoniazid-treated rats. In conclusion, dimeric polyphenols and galloylated derivatives of plant origin are unlikely to influence the initiation stage of the carcinogenicity of chemicals through mechanisms that involve inhibition of their cytochrome P450-mediated bioactivation or scavenging of the reactive, genotoxic intermediates.

Animals↗
PubMed2000

Histopathology and polyphenol content in plants infected by phytoplasmas.

The alterations of cell walls and the localization of several compounds such as polyphenols, suberin, lignin, in plum and apple plants infected with plum leptonecrosis (PLN) and apple proliferation (AP) phytoplasmas respectively, were investigated. Catharanthus roseus plants, infected with AP or PLN were also studied. The 4,6-diamidino-2-phenylindole (DAPI) test and transmission electron microscopy showed the presence of phytoplasmas in all infected plants. Specific histological stainings for cutinized/suberinized cell walls, tannin deposits and vacuolar polyphenol inclusions, performed on leaf and stem tissues, revealed an increase of these substances in infected plum and apple plants. No differences occurred in C. roseus. Total polyphenol analysis confirmed a strong increase (3-fold) in the polyphenol content in infected tissues, particularly in plum leaves. From the data obtained it appears that polyphenols can be considered as defence-related metabolites in plum and apple plants infected by phytoplasmas. Further investigations are necessary to determine whether these compounds play a specific role in the development of all phytoplasma/host interactions and in the defence-related processes.

Cell Wall↗
PubMed2002

[Effects of tea polyphenols and tea pigments on cell cycle of HepG2 cells].

The effects of tea polyphenols and tea pigments on cell cycle of hepatic cancer cells were studied. HepG2 cells were incubated with 50 and 100 mg/L tea polyphenols and tea pigments for 48 h respectively. Flow cytometry, Western blot and RT-PCR analysis were used. Flow cytometry analysis showed that tea polyphenols and tea pigments induced G1 arrest. Western blot analysis showed tea polyphenols and tea pigments significantly inhibited the expression of cyclin D1 protein and induced higher expression of P21WAFI/CIPI protein. The result of RT-PCR analysis demonstrated that Cdk4 was significantly inhibited by tea polyphenols and tea pigments. It is concluded that the induction of cell cycle arrest may be an important mechanism of tea on cancer prevention.

Carcinoma, Hepatocellular↗
PubMed1999

[Inhibitory effects of tea polyphenols and tea pigments on liver precancerous lesions in rats].

A liver precancerous model in rats was established with diethylnitorsamine(DEN) injected intraperitoneally as initiator and promoted by partial hepatectomy and injection of CCl4. The model was used to study the chemopreventive effect of tea polyphenols and tea pigments. A water solution of 0.1% tea polyphenols or tea pigments was given to Wistar rats as drinking water during the 56-day experiment period. A stable and sensitive early marker of liver cancer--GST-Pi positive foci or nodule was measured by a immunohistochemical method. Both tea polyphenols and tea pigments decreased the density and area of the GST-Pi foci. The expression of GST-Pi mRNA in chemical induced precancerous liver tissue was measured by Northern Blotting technique, and the expression of GST-Pi isoenzyme in liver tissue was detected by Western Blotting method. The results showed that both tea polyphenols and tea pigments effectively reduced the GST-Pi expression at both transcription and translation level. It is concluded that the inhibition of tea polyphenols and tea pigments on GST-Pi overexpression induced by chemical carinogen may be one of the mechanisms of their inhibition on the occurrence and progression of liver precancerous lesions in rats.

Animals↗