Standardized Green Tea Extract Research Articles

In Vivo Treatment with a Standardized Green Tea Extract Restores Cardiomyocyte Contractility in Diabetic Rats by Improving Mitochondrial Function through SIRT1 Activation.

Background. Green tea catechins are known to promote mitochondrial function, and to modulate gene expression and signalling pathways that are altered in the diabetic heart. We thus evaluated the effectiveness of the in vivo administration of a standardized green tea extract (GTE) in restoring cardiac performance, in a rat model of early streptozotocin-induced diabetes, with a focus on the underlying mechanisms. Methods. Twenty-five male adult Wistar rats were studied: the control (n = 9), untreated diabetic animals (n = 7) and diabetic rats subjected to daily GTE administration for 28 days (n = 9). Isolated ventricular cardiomyocytes were used for ex vivo measurements of cell mechanics and calcium transients, and molecular assays, including the analysis of functional protein and specific miRNA expression. Results. GTE treatment induced an almost complete recovery of cardiomyocyte contractility that was markedly impaired in the diabetic cells, by preserving mitochondrial function and energy availability, and modulating the expression of the sarcoplasmic reticulum calcium ATPase and phospholamban. Increased Sirtuin 1 (SIRT1) expression and activity substantially contributed to the observed cardioprotective effects. Conclusions. The data supported the hypothesis that green tea dietary polyphenols, by targeting SIRT1, can constitute an adjuvant strategy for counteracting the initial damage of the diabetic heart, before the occurrence of diabetic cardiomyopathy.

The Effect of Green Tea with EGCG Active Compound in Enhancing the Expression of M2 Microglia Marker (CD206).

Stroke is a neurological deficit due to vascular disorders. Microglia are the first line of defense against brain injury. Anti-inflammatory cytokines activate M2 microglia, which upregulate CD206. EGCG is abundant in green tea, which has an anti-inflammatory effect. To know the effect of green tea with its active compound EGCG on CD206 expression. True experimental trial design. Rattus Novergicus were divided into six groups: a negative control group (Sham), a positive control group (P0), MCAO mice given 10 mg/kg BW EGCG (P1), 20 mg/kg BW EGCG (P2), 30 mg/kg BW EGCG (P3), and 30 mg/kg BW standardized green tea extract (P4). CD206 expression was measured using immunohistochemistry and scored according to the Allred scoring guidelines. Descriptive test, Levine test, Kolmogorov-Smirnoff test, Independent sample t test, Pearson correlation test. We discovered that there is a significant difference in CD206 expression between the Sham and P0 groups (P < 0.05). In addition, there are significant differences in expression between the sham group and the other two groups (P1 and P2) (P < 0.05). Furthermore, when we compared the P0 group with each treatment group, we found that CD206 expression between P0-P2, P0-P3, P0-P4 are significantly different. There is a significant correlation between green tea with its active compound EGCG and CD206 expression enhancement. The correlation is positive. Green tea with EGCG active compound increases CD206 expression as an M2 marker in the Rattus norvegicus with MCAO model.

Efficacy of a Polyphenolic, Standardized Green Tea Extract for the Treatment of COVID-19 Syndrome: A Proof-of-Principle Study

The lack of therapies for moderate COVID-19 syndrome prompted us to use a standardized polyphenolic green tea extract rich in catechins during the lockdown due to the pandemic in Italy (Autumn 2020). Catechins are powerful antioxidant, anti-inflammatory and antiviral agents that are safe for human use. While awaiting hospitalization, 10 swab-positive patients, symptomatic for SARS-COV-2, were treated for 15 days at home with two sessions of inhalation plus three capsules per day (total catechins: 840 mg; total EGCG: 595 mg). All patients recovered fully and had no symptoms at a median of 9 days, with a range of 7–15 days. Seven switched to a negative SARS-COV-2 nasopharyngeal swab test at a median of 9 days, with a range of 6–13 days. Among the 3 patients still swab-positive, one had a strong decrease of infection down to a “very low” SARS-COV-2 nucleic acid load at 5 days. All patients exited quarantine at the end of therapy because they were free of symptoms. Inflammation markers α-1 anti-trypsin, C-reactive protein and eosinophils had significantly decreased. The IL-6 and erythrocyte sedimentation rate decreased in 7 out of 10 patients. To the best of our knowledge, this is the first report of the efficacy of green tea catechin against COVID-19 syndrome. These results may open new perspectives in the fight against the disease.

Prevention of Lipid Peroxidation-derived Cyclic DNA Adduct and Mutation in High-Fat Diet-induced Hepatocarcinogenesis by Theaphenon E.

Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role. We carried out a bioassay in the high-fat diet (HFD)-fed C57BL/6J mice to provide insight into the mechanisms of obesity-related HCC by studying γ-OHPdG, a mutagenic DNA adduct derived from lipid peroxidation. In an 80-week bioassay, mice received a low-fat diet (LFD), high-fat diet (HFD), and HFD with 2% Theaphenon E (TE) (HFD+TE). HFD mice developed a 42% incidence of HCC and LFD mice a 16%. Remarkably, TE, a standardized green tea extract formulation, completely blocked HCC in HFD mice with a 0% incidence. γ-OHPdG measured in the hepatic DNA of mice fed HFD and HFD+TE showed its levels increased during the early stages of NAFLD in HFD mice and the increases were significantly suppressed by TE, correlating with the tumor data. Whole-exome sequencing showed an increased mutation load in the liver tumors of HFD mice with G>A and G>T as the predominant mutations, consistent with the report that γ-OHPdG induces G>A and G>T. Furthermore, the mutation loads were significantly reduced in HFD+TE mice, particularly G>T, the most common mutation in human HCC. These results demonstrate in a relevant model of obesity-induced HCC that γ-OHPdG formation during fatty liver disease may be an initiating event for accumulated mutations that leads to HCC and this process can be effectively inhibited by TE. Cancer Prev Res; 11(10); 665-76. ©2018 AACR.

Standardized Morinda citrifolia L. and Morinda elliptica L. leaf extracts alleviated fatigue by improving glycogen storage and lipid/carbohydrate metabolism.

The antifatigue properties of Morinda elliptica (ME) leaf were compared with Morinda citrifolia (MC) leaf extracts. Sixty Balb/C mice were administered (N=10): control water, standardized green tea extract (positive control 200mg/kg body weight [BW]), either 200 or 400mgMC/kg BW, or either 200 or 400mgME/kg BW). The mice performances, biochemical, and mRNA expressions were evaluated. After 6weeks, the weight-loaded swimming time to exhaustion in the mice consuming 400mgMC/kg, were almost five times longer than the control mice. The gene expressions analysis suggested the extracts enhanced performance by improving lipid catabolism, carbohydrate metabolism, electron transport, antioxidant responses, energy production, and tissue glycogen stores. The MC and ME extracts enhanced stamina by reducing blood lactate and blood urea nitrogen levels, increasing liver and muscle glycogen reserve through augmenting the glucose metabolism (glucose transporter type 4 and pyruvate dehydrogenase kinase 4), lipid catabolism (acyl-Coenzyme A dehydrogenases and fatty acid translocase), antioxidant (superoxide dismutase 2) defence responses, electron transport (COX4I2), and energy production (PGC1α, NRF1, NRF2, cytochrome C electron transport, mitochondrial transcription factor A, UCP1, and UCP3) biomarkers. The MC (containing scopoletin and epicatechin) was better than ME (containing only scopoletin) or green tea (containing epicatechin and GT catechins) for alleviating fatigue.

Polyphenon E Treatment Alters Gene Expression in Prostate Cancer Cells

Prostate cancer (PCa) is the most common cancer among men in the United States. Polyphenon E (Poly E) is a standardized caffeine‐free green tea extract. Poly E has been reported to have chemopreventative activity against prostate cancer. The molecular mechanisms of this chemopreventative activity are not fully understood, however, the major constituent of Poly E, epigallocatechin‐3‐gallate (EGCG), has been reported to alter expression of some genes. It was hypothesized that Poly E treatment induces gene expression changes, which could provide insights to its molecular mechanism. The purpose of this experimental work was to identify genes that experienced substantially altered gene expression levels (changes 3‐fold or more) after Poly E treatment. Three human prostate cancer cell lines (DU 145, PC‐3, and LNCaP) were treated at three concentrations of Poly E (low, mid, high). Total cellular RNA was isolated from Poly E‐treated (and untreated) cells using RNA Easy Plus Miniprep Kit (Qiagen). RNA samples were subjected to qualitative and quantitative analysis using a BioAnalyzer RNA Chip (Agilent) at the Molecular Genomics Core facility at Moffitt Cancer Center. Analyzed RNAs at the mid‐concentration treatment were used for DNA microarray analyses with an Affymetrix Human U133 Plus 2.0 arrays. From the analysis of the microarray data acquired, numerous genes were identified with altered gene expression levels (increased or decreased &gt;3‐fold) after Poly E treatment. From this list, selected genes were analyzed by TaqMan qRT‐PCR using the ΔΔCt method in a StepOne™ RT‐PCR System. Reported RQ values were reported as fold changes. Analyzed RNAs were converted into cDNA with DyNAmo cDNA Synthesis Kit (Fischer Scientific) and were used as templates for qRT‐PCR. Untreated samples served as the reference control and ACTB served as the endogenous control. At the highest Poly E concentrations tested, TaqMan qRT‐PCR results for SEC62 were consistent with less than three‐fold gene expression changes for all cell lines studied (2.0‐fold increase in DU 145, 1.8‐fold increase in PC‐3, 2.1‐fold decrease in LNCaP). WNT9a gene expression levels experienced minor changes at the highest treatment level in PC‐3 and LNCaP cell lines (decreased 1.4‐fold, increased 1.4‐fold, respectively), however, increased 7.8‐fold in DU 145 cells. RB1 expression levels decreased by 3.1‐fold in PC‐3 cells, but remained essentially unchanged in DU 145 and LNCaP (both increased 1.2‐fold). MXD1 gene expression levels increased by 5.6‐fold in PC‐3 cells and 13.0‐fold in DU 145, but remained essentially unchanged (increased 1.1‐fold) in LNCaP. RGS4 gene expression levels experienced a 102‐fold increase in DU 145 and a 5.1‐fold increase in PC‐3 cells, while LNCaP cells exhibited a 5.6‐fold decrease. DU 145 cells experienced increased gene expression levels for all genes analyzed, while LNCaP cells had either a marginal increase of less than 2‐fold (WNT9a, RB1, MXD1) or a substantial decrease in the gene expression level (SEC62 decreased 2.1‐fold; RGS4 decreased 5.6‐fold). Collectively, these data could provide insights into new avenues for the development of biomarker or therapeutic interventions for prostate cancer.Support or Funding InformationThis work was financially supported by a University of Tampa David Delo Research Professor Grant (PI: L. M. Carastro), a University of Tampa Dana Research Professor Grant (PI: L. M. Carastro). This work was also supported by funding from the Department of Chemistry, Biochemistry &amp; Physics at the University of Tampa to support student research. We acknowledge the Moffitt Cancer Center Genomic Core Facility for excellent technical support in performing DNA microarray analyses.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Oxidative stress-induced Akt downregulation mediates green tea toxicity towards prostate cancer cells

Green tea consumption has been shown to possess cancer chemopreventive activity. Polyphenol E (PE) is a widely used standardized green tea extract formulation. This study was designed to investigate the impact of PE on prostate cancer cells (PC3), analyze the potential signals involved and elucidate whether anti- or pro-oxidant effects may be implicated. Treatment of PC3 cells with 30 and 100μg/ml PE significantly decreased cell viability and proliferation. At the tested concentrations, PE did not exert any antioxidant activity, eliciting instead a pro-oxidant effect at concentrations 30 and 100μg/ml, which was consistent with the observed PE cytotoxicity. PE-induced cell death was associated with mitochondrial dysfunction and downregulation of Akt activation, thus suggesting their implication in the PE-elicited cell dysfunction. Cell exposure to the ROS scavenger N-Acetyl Cysteine prevented PE-induced ROS increase, pAkt impairment, and cell death, clearly indicating the causative role of ROS in the observed phenomena. Failure of PE to induce PC3 damage in cells overexpressing Akt further confirms its implication in the PE-elicited cell death. Our findings showed an association between the antiproliferative and the pro-oxidant effect elicited by PE on PC3 cells and delineates a molecular signaling pattern potentially implicated in the toxicity of PE towards prostate cancer cells.

Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses

Morinda citrifolia fruit, (noni), enhanced performances in athletes and post-menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti-inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery.

Polyphenon E®, a standardized green tea extract, induces endoplasmic reticulum stress, leading to death of immortalized PNT1a cells by anoikis and tumorigenic PC3 by necroptosis

Increasing doses of Polyphenon E®, a standardized green tea extract, were given to PNT1a and PC3 prostate epithelial cells mimicking initial and advanced stages of prostate cancer (PCa), respectively. Cell death occurred in both cell lines, with PNT1a being more sensitive [half-maximal inhibitory concentration (IC50) = 35 μg/ml] than PC3 (IC50 = 145 μg/ml) to Polyphenon E®. Cell cycle arrest occurred at G0/G1 checkpoint for PNT1a, and G2/M for PC3 cells. Endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) occurred in both cell lines, with each exhibiting different timing in response to Polyphenon E®. Autophagy was transiently activated in PNT1a cells within 12 h after treatment as a survival response to overcome ERS; then activation of caspases and cleavage of poly (ADP ribose) polymerase 1 occurred, committing cells to anoikis death. Polyphenon E® induced severe ERS in PC3 cells, causing a dramatic enlargement of the ER; persistent activation of UPR produced strong upregulation of GADD153/CHOP, a key protein of ERS-mediated cell death. Thereafter, GADD153/CHOP activated Puma, a BH3-only protein, committing cells to necroptosis, a programmed caspase-independent mechanism of cell death. Our results provide a foundation for the identification of novel targets and strategies aimed at sensitizing apoptosis-resistant cells to alternative death pathways.

Effect of camellia sinensis extract on the expression level of transcription factors and cytochrome p450 genes coding phase i drug-metabolizing enzymes

Abstract Green tea (Camellia sinensis) is widely used as a popular beverage and dietary supplement that can significantly reduce the risk of many diseases. Despite the widespread use of green tea, the data regarding the safety as well as herb-drug interactions are limited. Therefore, the aim of our study was to assess the influence of standardized green tea extract (GTE) containing 61% catechins and 0.1% caffeine on the expression level of rat CYP genes and the corresponding transcription factors expression by realtime PCR. The findings showed that GTE resulted in a significant decrease of CYP2C6 expression level by 68% (p&lt;0.001). In case of CYP3A1 and CYP3A2, the mRNA levels were also reduced by extract but in a lesser degree compared to CYP2C6. Simultaneously the significant increase in the mRNA level of CAR, RXR and GR factors was observed by 54% (p&lt;0.05), 79% (p&lt;0.001) and 23% (p&lt;0.05), respectively after 10 days of green tea extract administration. In addition, there was noted a small increase of CYP1A1 expression level by 21% (p&gt;0.05) was noted. No statistically significant differences were observed for CYP1A2 and CYP2D1/2. In the same study we observed an increase in amount of ARNT gene transcript by 27% (p&lt;0.05) in the long-term use. However, green tea extract showed the ability to stimulate HNF-1α both after 3 and 10 days of treatment by 30% (p&lt;0.05) and 80% (p&lt;0.001), respectively. In contrast, no change was observed in the concentration of HNF-4α cDNA. These results suggest that GTE may change the expression of CYP enzymes, especially CYP2C6 (homologue to human CYP2C9) and may participate in clinically significant interactions with drugs metabolized by these enzymes.

Abstract A58: Green tea and silybin for breast cancer: A pilot presurgical study

Abstract The importance of new effective agents for breast cancer chemoprevention is highlighted by the fact that to date tamoxifen and raloxifene administration has not been completely accepted to reduce breast cancer risk, mostly because they are both associated with rare but serious toxic effects. Moreover, while SERMs and aromatase inhibitors do prevent the development of many ER-positive breast cancers, these drugs do not reduce the risk of ER-negative breast cancer. These results show that new approaches are needed also for the prevention of the latter. Phytochemicals present in fruits, vegetables, wine, and some medical herbs, especially botanical polyphenolic antioxidants, have received increasing attention in the last decade as potential chemopreventive agents for different human cancers. However, so far there is a limited knowledge of the processes regulating the absorption of phytochemicals (and/or their metabolites) into the body, and how they reach their biological target. In spite of epidemiological studies and scientific evidences supporting the beneficial role of phytochemicals in blocking cancer initiation and progression, the trials have though failed to yield predicted results in randomized intervention studies. Treatment in a window of opportunity (WOP) before surgery may improve clinical benefits and represents a very useful tool in selecting new chemopreventive agents against breast cancer. With this approach we will be able to study the kinetics of phytochemicals on the target organ as well as the effect on cell proliferation and other biomarkers by comparing the difference between pre- and post-treatment specimens. In the present pilot pre-surgical trial, we will study the bioavailability of two natural products formulated in a phosphatydilcholine complex, Greenselect® Phytosome® (a standardized caffeine-free green tea extract) and Siliphos® (the polyphenolic flavonoid silybin isolated from milk thistle) in breast cancer tissue. Ten histologically confirmed primary breast cancer patients will receive Greenselect® Phytosome® 300 mg / day and ten patients will receive Siliphos® 2.8 g / day for four weeks before surgery. The primary endpoint is to assess the concentration of the active ingredients and their metabolites by high performance liquid chromatography (HPLC) in plasma, tumor and surrounding non-neoplastic tissues. The study may provide important information for the development of future phase II clinical trials, specifically designed to explore the possible role of these two natural products in breast carcinogenesis. Moreover, the study will help to understand the biology and mechanisms of action of these potential chemopreventive agents. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A58.

Sustained Systemic Delivery of Green Tea Polyphenols by Polymeric Implants Significantly Diminishes Benzo[a]pyrene-Induced DNA Adducts

The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or via drinking water (0.8% w/v) to female S/D rats. Animals were treated with continuous low dose of benzo[a]pyrene (BP) via subcutaneous polymeric implants (2 cm; 10% load) and euthanized after 1 and 4 weeks. Analysis of lung DNA by (32)P-postlabeling resulted in a statistically significant reduction (50%; p = 0.023) of BP-induced DNA adducts in the implant group; however, only a modest (34%) but statistically insignificant reduction occurred in the drinking water group at 1 week. The implant delivery system also showed significant reduction (35%; p = 0.044) of the known BP diolepoxide-derived DNA adduct after 4 weeks. Notably, the total dose of poly E administered was >100-fold lower in the implant group than the drinking water group (15.7 versus 1,632 mg, respectively). Analysis of selected phase I, phase II, and nucleotide excision repair enzymes at both mRNA and protein levels showed no significant modulation by poly E, suggesting that the reduction in the BP-induced DNA adducts occurred presumably due to known scavenging of the antidiolepoxide of BP by the poly E catechins. In conclusion, our study demonstrated that sustained systemic delivery of poly E significantly reduced BP-induced DNA adducts in spite of its poor bioavailability following oral administration.

Abstract 5715: Green tea polyphenols implants are more effective than oral dosing in inhibiting benzo[a]pyrene-induced DNA adducts

Abstract Green tea is drawing increasing attention due to its potential chemopreventive effect. The polyphenols, including epigallocatechin gallate, epicatechin gallate, epigallocatechin and epicatechin in green tea, are believed to be the active components. However, epidemiological and clinical studies have shown mixed results presumably due to lack of bioavailability when given orally. In this study, polyphenon E, a standardized green tea extract, was administered by novel polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or by drinking water (0.8% w/v) to female S/D rats. Animals were then challenged with subcutaneous benzo[a]pyrene (BP) implants (2 cm; 10% load), and euthanized after 1 week. Analysis of the lung DNA by 32P-postlabeling showed a significant reduction (50%; p=0.023) in BP-induced DNA adducts in the implant group. A modest (34%) but statistically insignificant adduct reduction was also observed in the drinking water group. The dose of polyphenon E administered by implants was found to be &amp;gt;100 times lower than that by oral route (15.7 mg vs. 1,632 mg). No evidence of toxicity associated with either the polymeric materials or the compounds was found in all these groups based on the body weight and tissue weights. To determine possible mechanisms of action of polyphenon E, we analyzed CYP1A1, CYP1B1 and GST at mRNA and protein expression levels and for the enzyme activities. However, no evidence was found for favorable modulation of these phase I and phase II enzymes by polyphenon E. In in vitro studies, reaction of benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) with DNA was found to be strongly inhibited by individual catechins, particularly epigallocatechin gallate, present in polyphenon E, suggesting quenching of the electrophilic metabolite by the catechins. This notion was confirmed by reaction of anti-BPDE with individual catechins by LC/MS/MS. In conclusion, our study demonstrated that i) the effective dose of polyphenon E administered by polymeric implants was over 100-fold lower than the traditional oral route; and ii) polyphenon E exert their chemopreventive effect, at least, in part, due to direct quenching of anti-BPDE (Supported from CA-118114, KLCRP grant and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5715.

Green tea catechins inhibit angiogenesis through suppression of STAT3 activation

Previous studies indicate that green tea extract may inhibit breast cancer progression by blocking angiogenesis, although the molecular mechanisms are not well defined. We demonstrate that administration of Polyphenon E (Poly E), a standardized green tea extract, inhibited MDA-MB231 breast cancer and human dermal microvascular endothelial (HMVEC) cell migration and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9). In addition, Poly E inhibited VEGF-induced neovascularization in vivo. We also demonstrate that Poly E blocked signal transducers and activators of transcription (STAT) signaling by suppressing interferon-gamma (IFN-gamma)-induced gene transcription via IFN-gamma-activating sequence (GAS) elements and downstream STAT3 activation by inhibiting STAT1 and STAT3 dimerization in MDA-MB231 cells. Transient expression of constitutively active STAT3 significantly reduced the inhibitory effect of Poly E on cell migration and VEGF and MMP9 expression. Taken together, these observations indicate that green tea extract inhibits angiogenesis partly through the disruption of STAT3-mediated transcription of genes, including VEGF.

Novel approaches to chemoprevention of skin cancer.

Protection against sun-induced damage leading to photocarcinogenesis in skin is a highly desirable goal. Among various strategies, chemopreventive approaches utilizing non-toxic agents to prevent the occurrence of precancerous lesions or their surrogate markers are potentially attractive. Epidemiological and experimental studies provide evidence that some naturally occurring chemical agents in the human diet can diminish cancer risk. Aside from water, tea is the most common beverage consumed worldwide. Black tea accounts for nearly 80% of total tea production. Black tea and green tea are derived from the same plant, Camelia sinensis. Green tea contains monomeric polyphenols known as flavanols and black tea contains dimeric flavanols and polymeric polyphenols known as theaflavins (TFs) and thearubigins (TRs). Over the past fifteen years our laboratory has been exploring the feasibility of using tea and its constitutents as an approach to skin cancer prevention. We demonstrated that green tea, black tea and constituent polyphenols protect against chemical- and ultraviolet B (UVB)-induced carcinogenesis and reduce the growth of established tumors in skin. We have also shown the efficacy of green and black tea extracts against UVB and psoralen + ultraviolet A (PUVA)-induced early damage in skin. Although PUVA is highly effective in treating certain skin diseases, careful follow-up studies of cohorts of patients have shown that similar to UVB, PUVA treatment increases the risk for cutaneous squamous cell carcinoma and melanoma. We have found that oral administration of a standardized green tea extract (SGTE) prior to and during treatment of SKH-1 mice diminished PUVA-induced skin hyperplasia and hyperkeratosis. SGTE-treatment also inhibited PUVA-induced accumulation of c-fos and p53 proteins and epithelial hyperproliferation. Both topical application and oral administration of SGTE after PUVA-treatment reduced skin inflammation and cell hyperproliferation. Topical application of SGTE to human skin prior to PUVA-treatment inhibited the delayed skin inflammatory response. Similarly, oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic sub-fractions protect against UVB-induced erythema in SKH-1 mice. Furthermore, topical application of tea extracts to human volunteers protects against UVB-induced erythema. In summary, these studies indicate that tea extracts are effective in reducing UVB- and PUVA-mediated DNA damage, expression of early response genes and early inflammatory changes in skin. These studies verify a conceptual rationale for employing naturally occurring dietary constitutents as an approach to cancer chemoprevention.

Green Tea Protects Against Psoralen Plus Ultraviolet A-Induced Photochemical Damage to Skin1

The use of psoralens combined with exposure to ultraviolet A radiation is a major form of treatment for psoriasis and a number of other common skin diseases. Although psoralen plus ultraviolet A treatment is highly effective, careful follow-up cohort studies have shown that it greatly increases risk for the development of cutaneous squamous cell carcinoma and melanoma. Strategies to reduce the risk of cancer development in psoralen plus ultraviolet A-treated populations are highly desirable. In prior studies, we demonstrated that green tea and constituent polyphenols protect against ultraviolet B-induced carcinogenesis and reduce the growth rate of established tumors in skin. In this study, we show that pre- and post-treatment with standardized green tea extract in psoralen plus ultraviolet A treatment populations abrogates the psoralen plus ultraviolet A-induced photochemical damage to skin. Intact mouse and human skin and reconstituted human skin were employed to assess the effect of both topical and oral administration of standardized green tea extract against psoralen plus ultraviolet A-induced photodamage. Oral administration of standardized green tea extract prior to and during multiple psoralen plus ultraviolet A treatments reduced hyperplasia and hyperkeratosis in murine skin. Standardized green tea extract treatment also inhibited accumulation of c-fos and p53 protein induction following a single exposure to psoralen plus ultraviolet A. c-fos and p53 positive cells in psoralen plus ultraviolet A-treated skin were found to be increased by 55.4 +/- 13. 6% and 62.3 +/- 10.5%, respectively, compared with saline-treated unexposed control skin. Oral administration of 0.4 or 0.8% standardized green tea extract inhibited c-fos protein accumulation by 18.5% and 46.2% (p < 0.05), respectively, and p53 protein accumulation by 26.1% and 54.3% (p < 0.05), respectively. Similarly proliferating cell nuclear antigen staining, a marker of cell proliferation was induced (73.7%) in psoralen plus ultraviolet A-treated skin. Oral administration of 0.4% or 0.8% standardized green tea extract 1 d after psoralen plus ultraviolet A treatment was effective in reducing psoralen plus ultraviolet A-induced inflammatory responses including erythema and edema formation. When standardized green tea extract was applied to EpiDerm, a reconstituted human skin equivalent, psoralen plus ultraviolet A-induced 8-methoxypsoralen-DNA adduct formation and p53 protein accumulation were inhibited. Topical application of 0.2 mg 8-methoxypsoralen per cm2 followed by exposure to ultraviolet A (2.5 J per cm2) resulted in delayed erythema formation in human subjects. Pretreatment of human skin with topical application of 0.2 mg standardized green tea extract per cm2 30 min prior to psoralen plus ultraviolet A treatment resulted in an almost complete abrogation of psoralen plus ultraviolet A-induced erythema. In summary, these data demonstrate that standardized green tea extract protects against psoralen plus ultraviolet A-induced phototoxicity by inhibiting DNA damage and diminishing the inflammatory effects of this modality.

GRAPE SEED EXTRACT COMPONENTS INDUCE STRESS SIGNALS IN A2780 HUMAN OVARIAN CELLS

This study attempted to identify possible regulatory sites and mechanisms of antiapoptotic flavan-3-ols, focusing on reactive oxygen species mediated signaling in A2780 ovarian cancer cells. The cells were treated different concentrations of some rich flava-3-ols extracts. The results obtained for grape seed extract were compared to those of a standardized green tea extract. A concentration of 5 mg/ml grape seed extract induced apoptosis, producing intracellular high levels of reactive oxygen species through mitochondrial pathway. We noticed that 2.5 mg/ml grape seed extract reduce the expression of TNFa and the cellular proliferation. The overall data indicate that grape seed extract posses a potent protective effect against ovarian cancer cells, with dose-dependent characteristics.