Green Tea Catechin Extract Research Articles

Effects of Standardized Green Tea Extract and Its Main Component, EGCG, on Mitochondrial Function and Contractile Performance of Healthy Rat Cardiomyocytes.

We recently showed that the long-term in vivo administration of green tea catechin extract (GTE) resulted in hyperdynamic cardiomyocyte contractility. The present study investigates the mechanisms underlying GTE action in comparison to its major component, epigallocatechin-3-gallate (EGCG), given at the equivalent amount that would be in the entirety of GTE. Twenty-six male Wistar rats were given 40 mL/day of a tap water solution with either standardized GTE or pure EGCG for 4 weeks. Cardiomyocytes were then isolated for the study. Cellular bioenergetics was found to be significantly improved in both GTE- and EGCG-fed rats compared to that in controls as shown by measuring the maximal mitochondrial respiration rate and the cellular ATP level. Notably, the improvement of mitochondrial function was associated with increased levels of oxidative phosphorylation complexes, whereas the cellular mitochondrial mass was unchanged. However, only the GTE supplement improved cardiomyocyte mechanics and intracellular calcium dynamics, by lowering the expression of total phospholamban (PLB), which led to an increase of both the phosphorylated-PLB/PLB and the sarco-endoplasmic reticulum calcium ATPase/PLB ratios. Our findings suggest that GTE might be a valuable adjuvant tool for counteracting the occurrence and/or the progression of cardiomyopathies in which mitochondrial dysfunction and alteration of intracellular calcium dynamics constitute early pathogenic factors.

Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota

Catechin-rich green tea extract (GTE) protects against nonalcoholic steatohepatitis (NASH) by alleviating gut-derived endotoxin translocation and hepatic Toll-like receptor-4 (TLR4)–nuclear factor κB (NFκB) inflammation. We hypothesized that intact GTE would attenuate NASH-associated responses along the gut–liver axis to a greater extent than purified (−)-epigallocatechin gallate (EGCG) or (+)-catechin (CAT). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF) diet, or the HF diet with 2% GTE, 0.3% EGCG or 0.3% CAT for 8 weeks prior to assessing NASH relative to endotoxemia, hepatic and intestinal inflammation, intestinal tight junction proteins (TJPs) and gut microbial ecology. GTE prevented HF-induced obesity to a greater extent than EGCG and CAT, whereas GTE and EGCG more favorably attenuated insulin resistance. GTE, EGCG and CAT similarly attenuated serum alanine aminotransferase and serum endotoxin, but only GTE and EGCG fully alleviated HF-induced NASH. However, hepatic TLR4/NFκB inflammatory responses that were otherwise increased in HF mice were similarly attenuated by GTE, EGCG and CAT. Each treatment also similarly prevented the HF-induced loss in expression of intestinal TJPs and hypoxia inducible factor-1α and the otherwise increased levels of ileal and colonic TNFα mRNA and fecal calprotectin protein concentrations. Gut microbial diversity that was otherwise lowered in HF mice was maintained by GTE and CAT only. Further, microbial metabolic functions were more similar between GTE and CAT. Collectively, GTE catechins similarly protect against endotoxin–TLR4–NFκB inflammation in NASH, but EGCG and CAT exert differential prebiotic and antimicrobial activities suggesting that catechin-mediated shifts in microbiota composition are not entirely responsible for their benefits along the gut–liver axis.

Efficacy of Pluronic F-127 gel containing green tea catechin extract on chronic periodontitis – A clinical study

Purpose: To evaluate the efficacy of pluronic F-127 gel containing green tea catechin extract as a local drug delivery system in the treatment of chronic periodontitis.
 Methods: A total of 20 chronic periodontitis patients participated as per the set inclusion and exclusion criteria. Complete scaling and root planing (SRP) was done for all subjects and pluronic F-127 gel containing green tea catechin was applied on one site. The contralateral site received SRP alone. The plaque index (PI), gingival index (GI), and probing pocket depth (PPD) were recorded at baseline and on the 28th day.
 Results: At the 28th-day follow-up, green tea catechin tooth sites showed significantly lower mean scores (GI = 0.55, p = 0.30 and PPD = 3.35 mm) than the corresponding SRP tooth sites (GI = 1.25, PI = 1.15, and PPD = 4.40 mm) (p < 0.05).
 Conclusion: When compared to scaling and root planing alone, the local drug delivery gel containing green tea catechin as an adjuvant was more effective in reducing the clinical parameters of periodontitis.
 Keywords: Adjuvant therapy, Camellia sinensis, Local drug delivery, Periodontal pocket

Evidence of noncovalent complexes in some natural extracts: Ceylon tea and mate extracts.

Considering the high complexity of natural extracts, because of the presence of organic molecules of different chemical nature, the possibility of formation of noncovalent complexes should be taken into account. In a previous investigation, the formation of bimolecular complexes between caffeine and catechins in green tea extracts (GTE) has been experimentally proven by means of mass spectrometric and 1 H nuclear magnetic resonance experiments. The same approaches have been employed in the present study to evaluate the presence of bimolecular complexes in Ceylon tea and mate extracts. The obtained results show that in the case of Ceylon tea extracts, protonated theaflavin is detectable, together with theaflavin/caffein complexes, while caffeine/catechin complexes, already detected in green tea, are still present but at lower concentration. This aspect is evidenced by the comparison of precursor ion scans performed on protonated caffeine for the two extracts. The spectra obtained in these conditions for GTE and Ceylon tea show that the complexes of caffeine with epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG), highy abundant in the case of GTE (signal-to-chemical noise ratio in the range 50-100), are negligible (signal-to-chemical noise ratio in the range 2-3) in the case of Ceylon tea. Mate extracts show the formation of bimolecular complexes involving caffeine but not catechins, and chlorogenic acid becomes responsible for other complex formation. Under positive ion and negative ion conditions, accurate mass measurements allow the identification of malealdehyde, chlorogenic acid, caffeine, two isomers of dicaffeoylquinic acid, rutin, and kaempferol-3-O-rutinoside. These data indicate that the formation of complexes in natural extracts is a common behavior, and their presence must be considered in the description of natural extracts and, consequently, in their biological activity.

Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia-TLR4-NFκB-Mediated Inflammation.

Catechin-rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin-TLR4 (Toll-like receptor-4)-NFκB (nuclear factor kappa-B) inflammation. This study aimed to define altered MS-metabolomic responses during high-fat (HF)-induced NASH that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin-TLR4-NFκB liver injury. Mice are fed a low-fat (LF) or HF diet for 12 weeks and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8 weeks. Global MS-based metabolomics and targeted metabolite profiling of catechins/catechin metabolites are evaluated. GTE in HF mice restores hepatic metabolites implicated in dyslipidemia insulin resistance, and inflammation. These include 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B-vitamins, and bile acids are inversely correlated with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites are positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites are identified in livers of GTE-treated mice, mostly as phase II conjugates of parental catechins or microbial-derived valerolactones. The defined anti-inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB-mediated liver injury in NASH.

Green Tea Catechin Extract Supplementation Does Not Influence Circulating Sex Hormones and Insulin-Like Growth Factor Axis Proteins in a Randomized Controlled Trial of Postmenopausal Women at High Risk of Breast Cancer

Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins. We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age=60.0 y) and 537 to the placebo group (474 completed; mean age=59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. Women in the GTE group had significantly higher blood total estradiol (16%; P=0.02) and bioavailable estradiol (21%; P=0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction=0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735.

The in Vivo Antioxidant Effects of (-)-Epigallocatechin-3-Gallate Consumption in Healthy Postmenopausal Women Measured by Urinary Excretion of Secondary Lipid Peroxidation Products.

The present study was carried out to determine whether the consumption of epigallocatechin (EGCG), the major bioactive green tea catechin, exerts a positive effect on lowering in vivo lipid peroxidation, a measure of oxidative stress, in healthy postmenopausal women. Urinary excretion of secondary lipid peroxidation products, a measure of in vivo lipid peroxidation, was determined in 40 participants randomly assigned to consume a green tea catechin extract (843.0 ± 44.0 mg EGCG/d) or placebo capsules for 12 months. Urine samples were analyzed for individual polar and nonpolar lipophilic aldehydes and related carbonyl compounds by high-performance liquid chromatography (HPLC) at the beginning and at the end of the 12-month intervention period. Results show that two nonpolar aldehydes, nonanal and decatrienal, were both 48% lower (p < 0.005) following consumption of EGCG. These results indicate that a modest degree of in vivo antioxidant activity exists with long-term EGCG consumption, which could slightly limit oxidative damage associated with lipid peroxidation and the onset and progression of chronic diseases.

Effects of green tea catechin extract on serum lipids in postmenopausal women: a randomized, placebo-controlled clinical trial

Background: Green tea has been suggested to improve cardiovascular disease risk factors, including circulating lipid variables. However, current evidence is predominantly based on small, short-term randomized controlled trials conducted in diverse populations.Objective: The aim of this study was to examine the efficacy and impact of green tea extract (GTE) supplementation high in epigallocatechin gallate (EGCG) on blood lipids in healthy postmenopausal women.Design: This was an ancillary study of a double-blind, randomized, placebo-controlled, parallel-arm trial investigating the effects of a GTE supplement containing 1315 mg catechins (843 mg EGCG) on biomarkers of breast cancer risk. Participants were randomly assigned to receive GTE (n = 538) or placebo (n = 537) and were stratified by catechol-O-methyltransferase (COMT) genotype activity (high COMT compared with low or intermediate COMT genotype activity). They consumed either 4 GTE or identical placebo capsules daily for 12 mo. A total of 936 women completed this substudy. Circulating lipid panels including total cholesterol (TC), HDL cholesterol, and triglycerides were measured at baseline and at months 6 and 12.Results: Compared with placebo, 1-y supplementation with GTE capsules resulted in a significant reduction in circulating TC (−2.1% compared with 0.7%; P = 0.0004), LDL cholesterol (−4.1% compared with 0.9%; P < 0.0001) and non-HDL cholesterol (−3.1% compared with 0.4%; P = 0.0032). There was no change in HDL-cholesterol concentration, but triglyceride concentrations increased by 3.6% in the GTE group, whereas they decreased by 2.5% in the placebo group (P = 0.046). A significant reduction in TC was observed only among women with high (i.e., ≥200 mg/dL) baseline TC concentrations (P-interaction = 0.01) who consumed GTE capsules. The effect of GTE on the increase in triglycerides was mainly observed among obese women and statin users (P-interaction = 0.06).Conclusion: Supplementation with GTE significantly reduced circulating TC and LDL-cholesterol concentrations, especially in those with elevated baseline TC concentrations. This trial was registered at clinicaltrials.gov as NCT00917735.

Systemic Absorption of Catechins after Intraruminal or Intraduodenal Application of a Green Tea Extract in Cows.

Green tea catechins have various potential health benefits in humans including anti-inflammatory, anti-oxidative and hepato-protective effects. If present in the circulation, they might have similar effects in ruminants, which are exposed to oxidative stress and fatty liver disease such as dairy cows during the periparturient phase. However, the bioavailability of a substance is a prerequisite for any post absorptive effect in vivo. This study aimed to investigate the appearance of catechins from a green tea extract (GTE) in cattle plasma after intraruminal and intraduodenal administration because absorption is of major importance regarding the bioavailability of catechins. The studies were performed in 5 rumen-fistulated non-lactating heifers and 6 duodenally fistulated lactating dairy cows, respectively, equipped with indwelling catheters placed in a jugular vein. The GTE was applied intraruminally (10 and 50 mg/kg BW, heifers) or duodenally (10, 20 and 30 mg/kg BW, dairy cows) in a cross‐over design with a 2 d washout period between different dosages. Blood samples were drawn following the GTE administration at various pre-defined time intervals. The concentration of the major GTE catechins (gallocatechin, epigallocatechin, catechin, epicatechin, epigallocatechin-gallate, epicatechin-gallate) in plasma samples were analysed by HPLC with electrochemical detection. Irrespective of the dose, almost none of the catechins originally contained in the GTE were detected in plasma samples after intraruminal application. In contrast, intraduodenal administration of GTE resulted in increased plasma concentrations of epicatechin, epigallocatechin, epigallocatechin gallate in a dose‐dependent manner. Thus, we can conclude that intraruminally or orally administered catechins are intensively metabolized by ruminal microorganisms.

Abstract CT122: A presurgical study of lecithin formulation of green tea extract in women with early breast cancer

Abstract Background: Epidemiologic data support an inverse association between green tea intake and breast cancer (BC) risk. Greenselect® Phytosome® (GSP) is a lecithin formulation of a caffeine-free green tea catechin extract. The purpose of the study was to determine the tissue distribution of Epigallocatechin 3-O-gallate (EGCG) and its effect on cell proliferation and other biomarkers in BC patients undergoing surgery. Methods: Twelve early BC patients received GSP, 300 mg daily for 4 weeks prior to surgery. The EGCG levels were measured before (free-) and after (total-) enzymatic hydrolysis by HPLC-MS/MS in plasma, urine, BC tissue and surrounding normal tissue. Fasting blood samples were taken at baseline, before the last administration and 2 hours later. Women were asked to avoid any tea for at least 14 days prior the beginning of the study and for the entire duration of the study. Results: All patients were fully compliant and completed the treatment program. No toxicity was observed. Free-EGCG and Total-EGCG were undetectable in baseline samples except for 1 patient with total-EGCG of 1 ng/mL in plasma. Despite a high between-subject variability, total EGCG was detectable in all tumor tissue samples collected (n = 8). Repeated administration of GSP achieved levels of total-EGCG ranging from 17 to 121 ng/mL in plasma, and up to 8 ng/g in BC tissue. Median total-EGCG concentration was higher in the tumor as compared to the adjacent normal tissue (P = 0.01).Urine EGCG levels correlated inversely with concentration in normal tissue (P = 0.01). Free-EGCG concentrations ranged from 8 to 65 ng/mL in plasma, but were under the limit of quantitation in tumor tissue and present in traces in adjacent normal breast tissue. Conclusions: Compared to other green tea extracts, GSP taken orally, appears to increase bioavailability of EGCG which selectively accumulates in breast tumor tissue. Biomarkers of activity will be presented at the conference. Median (Q1-Q3) concentrations after supplementation:Urine-final ng/mLPlasma-end ng/mLPlasma-end-2h ng/mLBreast-K ng/gBreast-N ng/gTotal-EGCG4.7 (3.3, 5.4)20.3 (14.7, 30.7)89.0 (50.9, 111.4)3.2 (2.7, 4.6)0.50 (0.5,2.3)end: before the last administration; end-2h: 2 hours after the last administration; value below the detectable level were imputed as 0.5. K: cancer tissue; N: normal tissue; P-value from Wilcoxon-rank test. Citation Format: Matteo Lazzeroni, Aliana Guerrieri-Gonzaga, Sara Gandini, Harriet Johansson, Davide Serrano, Pietro Caldarella, Gianmatteo Pagani, Paolo Arnone, Giancarlo Pruneri, Valentina Aristarco, Antonella Puccio, Serena Mora, Antonella Riva, Giovanna Petrangolini, Paolo Morazzoni, Bernardo Bonanni. A presurgical study of lecithin formulation of green tea extract in women with early breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT122.

Antioxidant activity and recovery of green tea catechins in full-fat cheese following gastrointestinal simulated digestion

Green tea extract (GTE) was incorporated into full-fat cheeses at 250, 500, and 1000ppm to investigate the effect of green tea catechins on antioxidant properties and microstructure of cheese, and recovery of catechins. Cheeses were ripened for 90 days at 8°C followed by simulated gastrointestinal digestion. The composition on Day 0, and pH, total phenolic content (TPC), and antioxidant activity (AA) of the cheeses on Days 0, 30, and 90, were determined. The concentrations of the major GTE catechins in the curd and from the digesta of mature cheeses were determined using HPLC. Addition of GTE significantly (p≤0.05) decreased the pH of whey and curd during cheese manufacture and ripening, however there was no significant (p>0.05) effect on moisture, protein, or fat contents. Addition of GTE increased TPC and AA at all concentrations, but in a non-linear manner. Individual catechins were selectively retained in the curd, whereas different portions were recovered from the cheese digesta. Transmission electron microscopy showed that the ripened control cheese had a regular distribution of milk fat globules entrapped in a homogeneous structure of casein proteins, which was disrupted by GTE. Interactions between green-tea catechins and cheese fat were confirmed by Fourier transform infrared spectroscopy.

Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells

To begin development of a mechanistically relevant humane alternative platform for safety assessment of dog food ingredients, comparative in vitro cytotoxicity of 20 ingredients was assessed in four canine cell types relevant for toxicity assessments. Previously, we described the toxicity of 13 compounds (clove leaf oil, eugenol, guanosine monophosphate [GMP], GMP plus inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol, lemon grass oil, xylitol, and citric acid) using in vitro primary canine cell culture models for liver, kidney, bone marrow-derived mesenchymal stem cells (BMSC), and enterocyte-like cells (ELC). In this report, dose–response cytotoxicity studies and LC50 using alamar blue assays are reported for seven additional compounds: denatonium benzoate, eucalyptol, hexahydroisohumulone, tetrahydroisohumulone, green tea catechin extract, epigallocatechin gallate, and sodium copper chlorophyllin. Data across 20 compounds were compared between different cell types and responses were not parallel, precluding the use of a single cell line for in vitro ingredient hazard assessment. Hepatocytes were most resistant to all compounds, consistent with their xenobiotic detoxification functions. BMSC and ELC showed an increase in sensitivity to the essential oils eucalyptol, eugenol, and thymol compared to renal cells and hepatocytes. These studies provide a baseline of acute cytotoxicity of 4 canine cell types to 20 different food components that begin to illustrate how such an in vitro panel could be used for hazard assessment.

Oxidative stress response in canine in vitro liver, kidney and intestinal models with seven potential dietary ingredients.

In vitro cell culture systems are a useful tool to rapidly assess the potential safety or toxicity of chemical constituents of food. Here, we investigated oxidative stress and organ-specific antioxidant responses by 7 potential dietary ingredients using canine in vitro culture of hepatocytes, proximal tubule cells (CPTC), bone marrow-derived mesenchymal stem cells (BMSC) and enterocyte-like cells (ELC). Cellular production of free radical species by denatonium benzoate (DB), epigallocatechin gallate (EPI), eucalyptol (EUC), green tea catechin extract (GTE) and sodium copper chlorophyllin (SCC), tetrahydroisohumulone (TRA) as well as xylitol (XYL) were continuously measured for reactive oxygen/nitrogen species (ROS/RNS) and superoxide (SO) for up to 24h. DB and TRA showed strong prooxidant activities in hepatocytes and to a lesser degree in ELC. DB was a weak prooxidant in BMSC. In contrast DB and TRA were antioxidants in CPTC. EPI was prooxidant in hepatocytes and BMSC but showed prooxidant and antioxidant activity in CPTC. SCC in hepatocytes (12.5mg/mL) and CPTC (0.78mg/mL) showed strong prooxidant and antioxidant activity in a concentration-dependent manner. GTE was effective antioxidant only in ELC. EUC and XYL did not induce ROS/RNS in all 4 cell types. SO production by EPI and TRA increased in hepatocytes but decreased by SCC in hepatocytes and ELC. These results suggest that organ-specific responses to oxidative stress by these potential prooxidant compounds may implicate a mechanism of their toxicities.

The Minnesota Green Tea Trial (MGTT), a randomized controlled trial of the efficacy of green tea extract on biomarkers of breast cancer risk: study rationale, design, methods, and participant characteristics.

The Minnesota Green Tea Trial (MGTT) was a randomized, placebo-controlled, double-blinded trial investigating the effect of daily green tea extract consumption for 12 months on biomarkers of breast cancer risk. Participants were healthy postmenopausal women at high risk of breast cancer due to dense breast tissue with differing catechol-O-methyltransferase (COMT) genotypes. The intervention was a green tea catechin extract containing 843.0 ± 44.0 mg/day epigallocatechin gallate or placebo capsules for 1 year. Annual digital screening mammograms were obtained at baseline and month 12, and fasting blood and 24-h urine samples were provided at baseline and at months 6 and 12. Primary endpoints included changes in percent mammographic density, circulating endogenous sex hormones, and insulin-like growth factor axis proteins; secondary endpoints were changes in urinary estrogens and estrogen metabolites and circulating F2-isoprostanes, a biomarker of oxidative stress. The MGTT screened more than 100,000 mammograms and randomized 1,075 participants based on treatment (green tea extract vs. placebo), stratified by COMT genotype activity (high COMT vs. low/intermediate COMT genotype activity). A total of 937 women successfully completed the study and 138 dropped out (overall dropout rate = 12.8 %). In this paper we report the rationale, design, recruitment, participant characteristics, and methods for biomarker and statistical analyses.

Calcium desensitizer catechin reverses diastolic dysfunction in mice with restrictive cardiomyopathy

Diastolic dysfunction refers to an impaired relaxation and an abnormality in ventricular blood filling during diastole while systolic function is preserved. Cardiac myofibril hypersensitivity to Ca2+ is a major factor that causes impaired relaxation of myocardial cells. The present study investigates the effect of the green tea extract catechins on myofibril calcium desensitization and restoration of diastolic function in a restrictive cardiomyopathy (RCM) mouse model with cardiac troponin mutations. Wild type (WT) and RCM mice were treated daily with catechin (epigallocatechin-3-gallate, EGCg, 50mg/kg body weight) for 3months. Echocardiography and cell based assays were performed to measure cardiac structure and flow-related variables including chamber dimensions, fraction shortening, trans-mitral flow patterns in the experimental mice. In addition, myocyte contractility and calcium dynamics were measured in WT and RCM cardiomyocytes treated in vitro with 5μM EGCg. Our data indicated that RCM mice treated with EGCg showed an improved diastolic function while systolic function remained unchanged. At the cellular level, sarcomere relaxation and calcium decay were accelerated in RCM myocardial cells treated with EGCg. These results suggest that catechin is effective in reversing the impaired relaxation in RCM myocardial cells and rescuing the RCM mice with diastolic dysfunction.

Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia

ObjectiveIn vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention. MethodsNinety-eight eligible women were randomized to receive either Polyphenon E (containing 800mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. ResultsPolyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)]. ConclusionBased on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.

Abstract C50: Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia

Abstract In vitro data and pilot clinical trial data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and its precursor lesions. We conducted a randomized, double-blind, placebo controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low grade cervical intraepithelial neoplasia (CIN1) to evaluate the potentials of Polyphenon E for cervical cancer prevention. Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Partial response, defined as clearance of oncogenic HPV with evidence of CIN1, occurred more frequently in the placebo group 6 (14.6%) vs. 1 (2.4%) in the Polyphenon E arm. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group [3 (7.7%) vs. 6 (14.6%) in the placebo arm, although neither of these observations were statistically significant. Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that four months of Polyphenon E intervention did not promote the clearance of persistent high risk HPV and related CIN 1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies. Citation Format: Tomas Nuno, Francisco A.R. Garcia, Terri Cornelison, Amy L. Mitchell, David L. Greenspan, John W. Byron, Chiu-Hsieh Hsu, David S. Alberts, Sherry Chow. Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C50.

Greenselect Phytosome for Borderline Metabolic Syndrome

The beneficial effects of Greenselect Phytosome, a proprietary lecithin formulation of a caffeine-free green tea catechin extract, were evaluated in a controlled registry study on 50 asymptomatic subjects borderline for metabolic syndrome factors and with increased plasma oxidative stress. After 24 weeks of intervention, improvement in weight, blood lipid profile, and blood pressure positioned 68% of subjects in the treatment arm out of the metabolic syndrome profile, while 80% of the subjects in the control group still remained in their initial borderline disease signature. Compared to the control (lifestyle and dietary changes alone), Greenselect Phytosome was especially effective for weight/waist changes. These results highlight the relevance of addressing multiple factors involved in the development of metabolic syndrome with a pleiotropic agent capable of improving the beneficial effects of lifestyle and dietary changes and foster the attainment of a globally improved health profile.

Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.

A Green Tea Catechin Extract Upregulates the Hepatic Low‐Density Lipoprotein Receptor in Rats

Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo in the rat. A green tea extract (GTE) enriched in its anti-oxidant constituents, the catechins, was fed to rats (n = 6) at concentrations of either 0, 0.5, 1.0 or 2.0% (w/w) mixed in with their normal chow along with 0.25% (w/w) cholesterol for 12 days. Administration of the GTE had no effect on plasma total or LDL cholesterol concentrations but high-density lipoprotein significantly increased (41%; p < 0.05). Interestingly, there was a significant increase in LDL receptor binding activity (2.7-fold) and LDL receptor protein (3.4-fold) in the 2% (w/w) treatment group compared to controls. There were also significant reductions in liver total and unesterified cholesterol (40%). Administration of the GTE significantly reduced cholesterol absorption (24%) but did not affect cholesterol synthesis. These results show that, despite no effect on plasma cholesterol, the GTE upregulated the LDL receptor in vivo. This appears to be via a reduction in liver cholesterol concentration and suggests that the green tea extract was able to increase the efflux of cholesterol from liver cells.