Activity Of Green Tea Polyphenols Research Articles

Structural Characteristics for Superoxide Anion Radical Scavenging and Productive Activities of Green Tea Polyphenols Including Proanthocyanidin Dimers

The purpose of this paper is to report structural characteristics for superoxide anion radical (O(2(-))) scavenging and productive activities of green tea polyphenols. (-)-Epicatechin 3-O-gallate (5), (-)-epigallocatechin (6), (-)-epigallocatechin 3-O-gallate (7), (+)-gallocatechin-(4alpha-->8')-epigallocatechin (8), and (-)-epigallocatechin-(2beta-->O-->7', 4beta-->8')-epicatechin 3'-O-gallate (9) were isolated from the tea plant Camellia sinensis L. (+)-Epigallocatechin-(2beta-->O-->7, 4beta-->8')-epicatechin (10) was prepared by hydrolyzing 9. The polyphenols, as well as commercially available pyrogallol (1), methyl gallate (2), (+)-catechin (3), (-)-epicatechin (4), and the flavonol myricetin (11), produced O(2(-)) in descending order 1, 6 asymptotically equal to11 asymptotically equal to8, 7, 10, 2 asymptotically equal to9, 5 asymptotically equal to4. In the polyphenols with the pyrogallol-type B-ring and/or galloyl group, electron-withdrawing substituents (carbonyl and ketal carbons) and/or intramolecular hydrogen bonding constituted structural characteristics against the autoxidation reaction. The O(2(-))-productive activity partially counteracted O(2(-))-scavenging activity. However, such structural characteristics appeared to enhance the scavenging activity, accordingly the polyphenols in effect served as O(2(-))-scavengers in descending order 9 asymptotically equal to7, 2, 11, 8, 10, 3 asymptotically equal to4. On the other hand, 6, having no such structural characteristic, acted as a O(2(-))-generator, as well as 1. Further assessments covering tannins (e.g., A-type proanthocyanidin dimer 9) are needed to identify which green tea polyphenols are the most desirable chemopreventive agents.

Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation

There is increasing evidence that green tea polyphenols can protect against myocardial damage. Recently, we showed that they bind to cardiac troponin C and alter myofilament Ca(2+) sensitivity in cardiac muscle. In the present study, we examined whether green tea extract (GTE) could prevent the progressive remodeling seen in ischemic myocardium and improve cardiac function by modulation of the contractile apparatus utilizing a myocardial infarction (MI) model in the rat involving ligation of the left anterior descending branch. Using this model, severe myocardial injury was found, including altered cardiac performance and the appearance of extensive fibrosis and left ventricular (LV) enlargement. Supplementation with 400 mg/kg/day of GTE for 4, 18, or 46 days had beneficial effects in preventing the hemodynamic changes. Histopathological studies showed that GTE attenuated the progressive remodeling seen after myocardial injury. Echocardiography confirmed that GTE prevented LV enlargement and improved LV performance in post-MI rats. In addition, we showed that GTE supplementation for 18 or 46 days increased the myofilament Ca(2+) sensitivity of the ischemic myocardium in post-MI rats. These results validate the novel action of green tea polyphenols in protecting against myocardial damage and enhancing cardiac contractility by modulating myofilament Ca(2+) sensitivity in post-MI rats.

Simultaneous Manipulation of Multiple Brain Targets by Green Tea Catechins: A Potential Neuroprotective Strategy for Alzheimer and Parkinson Diseases

Current therapeutic approaches for Alzheimer and Parkinson disease (AD and PD, respectively) are merely symptomatic, intended for the treatment of symptoms, but offer only partial benefit, without any disease-modifying activity. Novel promising strategies suggest the use of antiinflammatory drugs, antioxidants, iron-complexing molecules, neurotrophic factor delivery, inhibitors of the amyloid precursor protein (APP)-processing secretases, gamma and beta (that generate the amyloid-beta peptides, Abeta), anti-Abeta aggregation molecules, the interference with lipid cholesterol metabolism and naturally occurring plant flavonoids to potentially reverse the course of the diseases. Human epidemiological and new animal data suggest that tea drinking may decrease the incidence of dementia, AD, and PD. In particular, its main catechin polyphenol constituent (-)-epigallocatechin-3-gallate (EGCG) has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders. In the current article, we review the literature on the impact of the multimodal activities of green tea polyphenols and their neuroprotective effect on AD and PD.

Cell Signaling Pathways and Iron Chelation in the Neurorestorative Activity of Green Tea Polyphenols: Special Reference to Epigallocatechin Gallate (EGCG)

Although much progress has been made in understanding the pathogenesis of Alzheimer's disease (AD), the current therapeutic approaches are merely symptomatic, intended for the treatment of cognitive symptoms, such as disturbances in memory and perception. Novel promising strategies suggest the use of anti-inflammatory drugs, antioxidants including natural occurring plant flavonoids, iron-complexing molecules, neurotrophic factor delivery, inhibitors of the amyloid-beta protein precursor processing secretases, gamma and beta, that generate amyloid-beta peptides and the interference with lipid and cholesterol metabolism. Human epidemiological and new animal data suggest that tea drinking may decrease the incidence of dementia, AD and Parkinson's disease. In particular, its main catechin polyphenol constituent (-)-epigallocatechin-3-gallate (EGCG) has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders. This review provides a detailed overview on the multimodal activities of green tea polyphenols with emphasis on their iron chelating, neurorescue/neuroregenerative and mitochondrial stabilization action.

Targeting Multiple Neurodegenerative Diseases Etiologies with Multimodal-Acting Green Tea Catechins

Green tea is currently considered a source of dietary constituents endowed with biological and pharmacological activities relevant to human health. Human epidemiological and new animal data suggest that the pharmacological benefits of tea drinking may help to protect the brain as we age. Indeed, tea consumption is inversely correlated with the incidence of dementia and Alzheimer’s and Parkinson’s diseases. In particular, its main catechin polyphenol constituent (−)-epigallocatechin-3-gallate has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders. The intense efforts dedicated in recent years to shed light on the molecular mechanisms participating in the brain protective action of green tea indicate that in addition to the known antioxidant activity of catechins, the modulation of signal transduction pathways, cell survival/death genes, and mitochondrial function all contribute significantly to the induction of neuron viability. Because of the multietiological character of neurodegenerative disease pathology, these natural compounds are receiving significant attention as therapeutic cytoprotective agents that simultaneously manipulate multiple desired targets in the central nervous system. This article elaborates on the multimodal activities of green tea polyphenols with emphasis on their recently described neurorescue/neuroregenerative and mitochondrial stabilization actions.

Quenching of α,β-unsaturated aldehydes by green tea polyphenols: HPLC–ESI–MS/MS studies

The aim of this work was to investigate in vitro the quenching activity of green tea polyphenols against α,β-unsaturated aldehyde, using 4-hydroxy-nonenal (HNE) as prototype and HPLC–ESI–MS/MS techniques. HNE is the most abundant and genotoxic product of oxidation of dietary polyunsaturated fatty acids, and is believed to be involved in the early stage of colorectal carcinogenesis on account of its genotoxic potential. Both epigallocatechin gallate (EGCG, 1.0–3.5 mM), the main constituent of green tea polyphenols, and a green tea aqueous extract are able to quench HNE (50 μM) in colorectal physiomimetic conditions (10 mM phosphate buffer, pH 8.0, 37 °C), giving rise to the formation of six diastereomeric covalent adducts at the ring A of EGCG, as indicated by their ESI–MS/MS fragmentation pathways. The specificity of the adduction positions was explained by 1H NMR experiments. HNE quenching is pH-dependent and maximum at pH 8.0. ESI–MS analysis showed no formation of 4-hydroxy-2,3-epoxy-nonanal, or adduction of the epoxide to EGCG. This implies that too little hydrogen peroxide (1 mM, 24 h incubation, FOX-2 method) develops from auto-oxidation of EGCG in our aerobic experimental conditions to oxidize HNE to its corresponding epoxide, so this mechanism is not responsible for the compound's disappearance. EGCG and green tea extract also quenched acrolein, another genotoxic α,β-unsaturated aldehyde, giving one predominant adduct and minor isobaric species, probably due the adduction of acrolein at different positions of the EGCG ring A. These results suggest that EGCG and green tea extract, beside the proposed mechanisms of chemoprevention that target multiple cell-signaling pathways that control cell proliferation and apoptosis in cancer cells, can also prevent protein carbonylation in the tumor tissue environment, depending on the pH of the medium surrounding the tissue, the type of tumor, the stage of dysregulation of lipid peroxidation and, finally, the stage of carcinoma development.

Abstract 2102: Nanochemoprevention: Introducing a novel concept in cancer chemoprevention with a proof of principle for superior activity of green tea polyphenol epigallocatechin-3-gallate encapsulated in PLGA/PVA nanoparticles

Abstract Despite extensive efforts that have been put to prevent cancer through chemoprevention, lack of delivery of desired levels of bioactive agents thus limiting their bioavailability, remains a challenging issue for effective clinical outcome. Thus, there is a strong unmet need in the biomedical technology community to find novel tools for making chemoprevention a success. Because most biological processes including those that are cancer-related occur at nanoscale, nanoparticulate technology has emerged as a potential tool to diagnose and treat cancer. We considered that nanoparticulate technology can prove to be very useful in cancer chemoprevention by allowing for effective and targeted delivery of chemopreventive agents. This delivery system could overcome many biological, biophysical and biomedical barriers that the body stages. Here, for the first time we introduce a concept of ‘nanochemoprevention’. To demonstrate the proof of principle we selected green tea polyphenol epigallocatechin-3-gallate (EGCG) with which we have considerable experience. We encapsulated EGCG in Poly (DL-lactide-co-glycolide acid) (PLGA)/Polyvinyl alcohol (PVA) nanoparticles, hereafter referred to as nano-EGCG, and evaluated it for cytotoxic response against human prostate cancer (PCa) PC3, DU145, 22Rν1 and LNCaP cells. MTT assay showed that treatment of cells with PLGA/PVC nanoparticles alone had negligible effect on cell growth. Interestingly, nano-EGCG, compared to EGCG in PBS, produced remarkably superior effects. For PC3 cells, the IC50 value at 24 hours of nano-EGCG was 3.75 μM compared to 40 μM of EGCG in PBS; 3.75 μM of EGCG in PBS had no effect. These differential effects were persistent at 48 and 72 hours. Similar effects of nano-EGCG were observed in 22Rν1, LNCaP and DU145, other human PCa cells. EGCG in PBS treatment to cells is known to result in induction of apoptosis and inhibition of colony formation which is considered essential for its chemopreventive effects. Next series of experiments were conducted to determine the effect of nano-EGCG on apoptosis and colony formation potential of PC3 cells. Treatment of the cells for 48 hours with nano-EGCG led to significant induction of PARP cleavage in a dose dependent manner and modulation of bax and bcl2 ratio that favored apoptosis. Further, nano-EGCG treatment also led to a dramatic increase in the levels of annexin V, an early marker of apoptosis. We then performed a 2-dimensional colony formation assay to evaluate the effect of nano-EGCG on the cellular growth pattern of PC3 cells and observed a marked decrease in colony number. Validation of these cell culture data to animal model systems could pave way for developing new avenues for cancer chemoprevention.

(–)-Epigallocatechin Gallate, A Major Constituent of Green Tea, Poisons Human Type II Topoisomerases

(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea, and many of the therapeutic benefits of the beverage have been attributed to this compound. High concentrations of EGCG are cytotoxic and trigger genotoxic events in mammalian cells. Although this catechin affects a number of cellular systems, the genotoxic effects of several bioflavonoid-based dietary polyphenols are believed to be mediated, at least in part, by their actions on topoisomerase II. Therefore, the effects of green tea extract and EGCG on DNA cleavage mediated by human topoisomerase IIalpha and beta were characterized. The extract and EGCG increased levels of DNA strand breaks generated by both enzyme isoforms. However, EGCG acted by a mechanism that was distinctly different from those of genistein, a dietary polyphenol, and etoposide, a widely prescribed anticancer drug. In contrast to these agents, EGCG exhibited all of the characteristics of a redox-dependent topoisomerase II poison that acts by covalently adducting to the enzyme. First, EGCG stimulated DNA scission mediated by both isoforms primarily at sites that were cleaved in the absence of compounds. Second, exposure of EGCG to the reducing agent dithiothreitol (DTT) prior to its addition to DNA cleavage assays abrogated the effects of the catechin on DNA scission. Third, once EGCG stimulated topoisomerase II-mediated DNA cleavage, exposure to DTT did not effect levels of DNA strand breaks. Finally, EGCG inhibited the DNA cleavage activities of topoisomerase IIalpha and beta when incubated with either enzyme prior to the addition of DNA. Taken together, these results provide strong evidence that EGCG is a redox-dependent topoisomerase II poison and utilizes a mechanism similar to that of 1,4-benzoquinone.

Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells

Currently, there is no effective therapy for estrogen independent breast cancer. MDA-MB-231 is an estrogen receptor negative highly invasive human breast cancer cell line and has been used as a relevant model system to evaluate drugs with chemopreventive potential against highly invasive breast cancer phenotypes. Epidemiological studies though inconclusive have shown that consumption of Green Tea Polyphenols (GTP) reduces the incidence and progression of breast cancer. Green tea is an important source of antioxidants that may be useful for chemoprevention of cancer. Recently published preclinical study from our lab suggested that GTP and EGCG treatment inhibit proliferation and induce apoptosis of MDA-MB-231. In this study, we have evaluated apoptotic and anti-invasive activity of green tea polyphenols(GTP) and its principal constituent Epigallocatechin gallate(EGCG) in MDA-MB-231 human breast cancer cell line. In in-vitro human breast cancer model, EGCG and GTP induced apoptosis and significantly decreased invasion of breast cancer cells. Western blotting of MDA-MB-231 cell lysates from EGCG and GTP treated and untreated control revealed an increase in bax, reduction in bcl2 and PARP cleavage. Quantitative fluorescence labeling resulted in a 24-28% reduction in invasion through matrigel by EGCG and 15-23% reduction by GTP in a dose dependent manner. Focussed microarray analysis and reverse transcriptase polymerase chain reaction and zymogram analysis revealed inhibition of MMP-9 expression by polyphenol treatment. Furthermore, AKT was found to be inhibited both at the RNA and protein level by polyphenol treatment. Moreover EGCG and GTP decreased AKT phosphorylation as found out by western blotting for Phospho-AKT(Ser-473). Beta-catenin level was found to be decreased both in cytoplasm and nucleus. For the first time we report the connection of betacatenin and AKT modulation by GTP and EGCG as a possible mechanism for the induction of apoptosis in human breast cancer cells and also inhibition in their invasive capacity.

Modulatory efficacy of Green tea polyphenols on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide-induced oral carcinogenesis—A therapeutic approach

Green tea polyphenols (GTP) has been used as a chemopreventive agent world wide against chemically induced cancer. The present study is aimed to understand the therapeutic action of GTP on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide (4-NQO)-induced oral cancer over a period of 30 days at 200 mg/kg, p.o., Oral cancer was induced by painting 4-NQO for 8 weeks followed by administration of GTP after 22 weeks, for 30 days. Glycoconjugates such as hexose, hexosamine, sialicacid, fucose and mucoprotein were analysed. Expression of glycoconjugates was examined through histology and SDS-PAGE. Immunological markers such as circulating immune complex and mast cell density were studied. Oral cancer-induced animals showed a significant increase in levels of glycoconjugates and its expression, similar to that observed for immunological markers. Treatment with GTP altered the expression of glycoconjugates as well as immunological markers. The results suggest that GTP modulates both the expression of glycoconjugates and immunological markers resulting in regression of oral cancer.

Effect of liposome encapsulation of tea catechins on their accumulation in basal cell carcinomas

(-)-Epigallocatechin gallate (EGCG), the main active polyphenol in green tea, is associated with antioxidant and anticancer activities. The aim of this study was to evaluate the feasibility of using liposomes for intratumor distribution of EGCG and its derivative, (+)-catechin. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic surfactant in the presence of 15% ethanol were prepared. The physicochemical characteristics including vesicle size, zeta potential, drug entrapment, and drug release of liposomal formulations were determined. The liposomes containing EGCG were injected into basal cell carcinomas (BCCs), melanomas, and colon tumors to examine the tumor uptake of the drug. Liposomes were also incubated with a given number of BCC cells, and the cell viability was estimated. Almost no drug molecules were observed when free EGCG was administered to BCCs. EGCG encapsulated in liposomes with deoxycholic acid (DA) and ethanol increased drug deposition by 20-fold as compared to the free form. The larger vesicle size of this formulation was suggested to be the predominant factor governing this enhancement. The liposomes without ethanol showed low or negligible enhancement on EGCG uptake in BCCs. Liposomes protected EGCG from degradation, resulting in the induction of greater BCC death compared to that by free EGCG at lower concentrations. These results suggest that the intratumor injection of liposomes containing EGCG with moderate modification is an effective approach for increasing EGCG deposition in BCCs.

Effect of polymeric black tea polyphenols on benzo(a)pyrene [B(a)P]-induced cytochrome P4501A1 and 1A2 in mice

The chemopreventive activity of green tea polyphenols (GTPs) is, in part, due to modulation of cytochrome P450s (CYPs). To investigate the enzyme modulatory properties of major black tea polyphenols, the effect of decaffeinated black tea extract (DBTE) or polymeric black tea polyphenol (PBP) mix was studied on CYP1A1 and CYP1A2 in mouse tissues. Animals receiving 2.5% DBTE or 1% PBP mix or drinking water (15 days) were challenged with single oral benzo(a)pyrene (B(a)P) (1 mg/mouse) treatment on the 14th day. Liver and lung microsomes isolated after 24 h were analysed for CYP1A1 and CYP1A2, using biochemical substrate(s) and Western blot analysis. Treatment with 2.5% DBTE or 1% PBP mix did not significantly alter the basal activity and level of CYP1A1 and CYP1A2, whereas pretreatment with 2.5% DBTE or 1% PBP mix resulted in a significant decrease in both the activity and the level of B(a)P-induced CYP1A1 and CYP1A2 in liver and lungs. The PBP mix possesses enzyme modulatory properties exhibited by monomeric GTPs.

The Intermediate Filament Protein Vimentin Is a New Target for Epigallocatechin Gallate

Epigallocatechin gallate (EGCG) is the major active polyphenol in green tea. Protein interaction with EGCG is a critical step in the effects of EGCG on the regulation of various key proteins involved in signal transduction. We have identified a novel molecular target of EGCG using affinity chromatography, two-dimensional electrophoresis, and mass spectrometry for protein identification. Spots of interest were identified as the intermediate filament, vimentin. The identification was confirmed by Western blot analysis using an anti-vimentin antibody. Experiments using a pull-down assay with [3H]EGCG demonstrate binding of EGCG to vimentin with a Kd of 3.3 nm. EGCG inhibited phosphorylation of vimentin at serines 50 and 55 and phosphorylation of vimentin by cyclin-dependent kinase 2 and cAMP-dependent protein kinase. EGCG specifically inhibits cell proliferation by binding to vimentin. Because vimentin is important for maintaining cellular functions and is essential in maintaining the structure and mechanical integration of the cellular space, the inhibitory effect of EGCG on vimentin may further explain its anti-tumor-promoting effect.

Dietary Prevention of Cancer: Anticancer and Antiangiogenic Properties of Green Tea Polyphenols

Both epidemiological and laboratory studies have suggested an inverse association between consumption of green tea and the prevalence of some cancers. The anti-tumorigenicity of green tea has been related to its content of specific polyphenols. The molecular mechanisms underlying the anticancer and antiangiogenic effects of green tea polyphenols (GTPs) are currently under intensive investigation. The purpose of this article is to update a previous review on the effects and biological activities of GTPs in relation to their therapeutic usefulness in preventing cancer in humans [1]. GTPs mainly consist of catechins (3-flavanols), of which epigallocatechin gallate (EGCG) is the most abundant in green tea and the most extensively studied. Moreover, the biological effects reported for GTPs have been mainly associated to EGCG. New perspectives on the applications of dietary GTPs as potential therapeutic and preventive agents against cancer are presented. Keywords: camellia sinensis, catechins, green tea polyphenols, high performance liquid chromatography

Redifferentiation of human hepatoma cells induced by green tea polyphenols

A novel approach for the treatment of cancer is the differentiation therapy in which cancer cells are induced to attain a mature phenotype when exposed to differentiation inducers. To examine the effects of polyphenols extracted from green tea, i.e. ( – )-epicatechin (EC), ( – )-epigallocatechin (EGC), ( – )-epicatechin gallate (ECG) and ( – )-epigallocatechin gallate (EGCG), on the proliferation and redifferentiation of human hepatoma cell line SMMC-7721, we measured the changes of cell growth, cell surface charge and cell morphography after treament with green tea polyphenols. It was found that the growth curve of treated cells was decreased remarkably, cell surface charge of treated cells was decreased and the microvilli on the surface of treated cells were reduced obviously. It confirmed that green tea polyphenols could reverse malignant phenotypic characteristics and induced redifferentiation of SMMC-7721 cells. The ability of green tea polyphenols to inhibit reactive oxygen species (ROS)-mediated oxidative damage of DNA was also assessedin vitro by measuring the conversion of supercoiled pBR322 plasmid DNA to the open circular and linear forms. It was found that green tea polyphenols could significantly inhibit the oxidative damage of DNA induced by a water-soluble azo initiator 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). However, they could promote the oxidative damage of DNA induced by H2O2 and Fe2+ at high concentrations. The relationship between the anti-cancer activity and antioxidation-prooxidation activity of green tea polyphenols is discussed.

Inhibition of Phorbol Ester–Induced COX-2 Expression by Epigallocatechin Gallate in Mouse Skin and Cultured Human Mammary Epithelial Cells

Green tea polyphenols are reported to possess substantial antiinflammatory and chemopreventive properties. However, the molecular mechanism of chemopreventive activity of green tea polyphenols is not fully understood. An abnormally elevated level of cyclooxygenase-2 (COX-2) is implicated in the pathogenesis of carcinogenesis. In the present study, we found that pretreatment of the green tea extract enriched with catechin and epigallocatechin gallate (EGCG) by gavage inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. Similarly, EGCG downregulated COX-2 in TPA-stimulated human mammary epithelial cells (MCF-10A) in culture. To further elucidate the underlying mechanism of COX-2 inhibition by green tea extract and EGCG, we examined their effects on the activation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), which are upstream enzymes known to regulate COX-2 expression in many cell types. Pretreatment with EGCG as well as green tea extract caused a decrease in the activation of ERK. In addition, EGCG inhibited the catalytic activity of ERK and p38 MAPK, suggesting that these signal-transducing enzymes could be potential targets for previously reported antitumor promoting activity of EGCG.

Antioxidant effects of green tea polyphenols

The unprecedented interest in the antioxidant activity of green tea polyphenols (GTP) is due to the apparent health benefits of tea drinking and the experimental results with the polyphenols. The results suggest that the galloylated catechins show stronger antioxidant effect than that of nongalloylated catechins and the double bond in C ring also plays an important role in this effect. There are synergic effects between different catechins and the antioxidant effect of (+)-epimers is stronger than that of (−)-epimers. The active site to scavenge free radicals mainly locates in p-hydroxyl of phenol in gallic acid and hydroxyl of phenol in the pyrane also shows activity. The large π bond in chromane and benzene ring of catechin is the structure base for their antioxidant effects. The prevent effect of GTP against diseases and their redox regulation in cell signal pathway are very important to be studied in the future.

Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes

An aqueous solution of green tea polyphenols (GTP) was found to inhibit lipid peroxidation (LP), scavenge hydroxyl and superoxide radicals in vitro. Concentration needed for 50% inhibition of superoxide, hydroxyl and LP radicals were 10, 52.5 and 136 μg/ml, respectively. Administration of GTP (500 mg/kg b.wt.) to normal rats increased glucose tolerance significantly ( P<0.005) at 60 min. GTP was also found to reduce serum glucose level in alloxan diabetic rats significantly at a dose level of 100 mg/kg b.wt. Continued daily administration (15 days) of the extract 50, 100 mg/kg b.wt. produced 29 and 44% reduction in the elevated serum glucose level produced by alloxan administration. Elevated hepatic and renal enzymes produced by alloxan were found to be reduced ( P<0.001) by GTP. The serum LP levels which was increased by alloxan and was reduced by significantly ( P<0.001) by the administration of 100 mg/kg b.wt. of GTP. Decreased liver glycogen, after alloxan administration showed a significant ( P<0.001) increase after GTP treatment. GTP treated group showed increased antioxidant potential as seen from improvements in superoxide dismutase and glutathione levels. However catalase, LP and glutathione peroxidase levels were unchanged. These results indicate that alterations in the glucose utilizing system and oxidation status in rats increased by alloxan were partially reversed by the administration of the glutamate pyruvate transaminase.

Antioxidant activity of green tea polyphenols against lipid peroxidation initiated by lipid-soluble radicals in micelles

Antioxidant effects of the principal polyphenolic components extracted from green tea leaves, i.e., (−)-epicatechin (EC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin gallate (EGCG), against peroxidation of linoleic acid have been studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a lipid-soluble azo initiator di-tert-butyl hyponitrite (DBHN) and the reaction kinetics were followed by formation of linoleic acid hydroperoxides and consumption of the antioxidant. Kinetic analysis of the antioxidation process demonstrates that these green tea polyphenols are effective antioxidants in micelles used either alone or in combination with α-tocopherol (vitamin E), but their antioxidative behaviour and relative effectiveness are substantially different from those in the water-soluble initiator AMPAD-initiated peroxidations reported previously. The antioxidative action of the green tea polyphenols (GOHs) in DBHN-initiated peroxidation involves trapping the initiating tert-butoxyl radical and the propagating linoleic acid peroxyl radicals. However, the GOHs could not participate in the α-tocopherol recycling reaction as in the case of AMPAD-initiated reactions due to their very fast reaction with the initiating tert-butoxyl radical.

Effects of food factors on signal transduction pathways.

Consumption of plant-derived foods, especially fruits and vegetables, has been linked to decreased risk of cancer. Laboratory studies with animals and cells in culture have shown cancer preventive activity of chemicals isolated from soy, tea, rice and many green, yellow and orange fruits and vegetables. Using cell culture, transgenic mice and knockout mice models to examine the anti-cancer effects of these dietary factors at the molecular level, we found that (11) (-)-epigallocatechin gallate (EGCG), the major active polyphenol in green tea, and theaflavins, the major active components in black tea, inhibit epidermal growth factor (EGF)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation. At the same dose range that inhibited cell transformation, EGCG and theaflavins inhibited activator protein-1 (AP-1) activation. These compounds also inhibited ultraviolet B (UVB)-induced AP-1 and nuclear factor kappa B (NFkappaB)-dependent transcriptional activation; (2) resveratrol, found at high levels in grapes, inhibited cell transformation through the induction of apoptosis, mediated through JNK and p53-dependent pathways; (3) inositol hexaphosphate (InsP6), an active compound from rice and other grains, inhibited TPA- or EGF-induced transformation and signal transduction through its effects on phosphatidylinositol-3 kinase (PI-3) kinase; (4) phenethyl isothiocyanate (PEITC), which occurs as a conjugate in certain cruciferous vegetables, inhibited cell transformation corresponding with the induction of apoptosis. An elevation of p53 is required for PEITC-induced apoptosis. Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter-induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP-1 action but not through the activation of retinoic acid response element (RARE).