Activity Of Green Tea Catechins Research Articles

Microbial-Transferred Metabolites and Improvement of Biological Activities of Green Tea Catechins by Human Gut Microbiota.

Green tea catechins (GTCs) are dietary polyphenols with broad bioactivities that undergo extensive microbial metabolism in the human gut. However, microbial-transferred metabolites and their health benefits are not fully understood. Herein, the microbial metabolism of GTCs by human fecal microbiota and dynamic alteration of the microbiota were integrally investigated via in vitro anaerobic fermentation. The results showed that the human gut microbiota exhibited a strong metabolic effect on GTCs via UHPLC-MS/MS analysis. A total of 35 microbial-transferred metabolites were identified, far more than were identified in previous studies. Among them, five metabolites, namely EGCG quinone, EGC quinone, ECG quinone, EC quinone, and mono-oxygenated EGCG, were identified for the first time in fermented GTCs with the human gut microbiota. Consequently, corresponding metabolic pathways were proposed. Notably, the antioxidant, α-amylase, and α-glucosidase inhibitory activities of the GTCs sample increased after fermentation compared to those of the initial unfermented sample. The results of the 16S rRNA gene sequence analysis showed that the GTCs significantly altered gut microbial diversity and enriched the abundancy of Eubacterium, Flavonifractor, etc., which may be further involved in the metabolisms of GTCs. Thus, these findings contribute to a better understanding of the interactions between GTCs and gut microbiota, as well as the health benefits of green tea consumption.

Extraction Efficiency and Alpha-Glucosidase Inhibitory Activities of Green Tea Catechins by Different Infusion Methods.

Alpha-glucosidase is an important target for glycemic control with the aim of reducing the risk of type 2 diabetes (T2D). Green tea catechins have been reported to inhibit alpha-glucosidase activity as a potential beverage to control blood glucose levels. However, the effects of the daily infusion style of green tea on tea catechins and their activity remain unclear. In this study, the extraction efficiency of catechins was investigated for 12 green tea extracts (GTEs) infused with 70% ethanol (70% EtOH for 24 h, a favored solvent for catechin extraction), room temperature water infusion (RT H2O for 24 h, an easy way to drink tea), and hot water infusion (Hot H2O for 90 s, a standard way to drink tea). Eight catechins were quantified by HPLC, and the inhibitory effect of GTEs and their catechins on alpha-glucosidase was measured with both rat intestinal enzymes and human Caco-2 cells. The inhibitory mechanism was further analyzed in silico by docking catechins to human alpha-glucosidase using Molecular Operating Environment software. The results showed that total catechins and gallate catechins were efficiently extracted in the order of 70% EtOH, RT H2O, and Hot H2O, and the inhibitory activity against alpha-glucosidase also followed a similar order. Pearson correlation analysis indicated that the alpha-glucosidase inhibitory activity of GTEs was significantly positively correlated with the contents of total catechins, especially gallate catechins. Gallate catechins, such as EGCg and ECg, showed lower IC50 values than free catechins for the enzyme in both rats and humans. In silico simulation revealed that gallate catechins were bound to the different sites with free catechins, and the docking energy of gallate catechins was lower than that of free catechins. Taken together, our data indicated that the daily infusion style of green tea significantly impacted the extraction efficiency and alpha-glucosidase inhibitory activities of catechins, which will give us insight into the use of green tea catechins for glycemic control through efficient infusion.

A review on anti-cancer effect of green tea catechins

Abstract This article reviewed inhibitory activities of green tea catechins (GTCs) against various tumorigenesis and their suppressive effects on cancer cell progression, metastasis, and angiogenesis according to a great number of kinds of literature, and then summarized the mechanisms of tea catechins-mediated cancer prevention in various cancer types. Special emphasis was placed on summarizing recent research highlighting the related techniques in improving GTCs’ effectiveness in the prevention of tumor progression and/or treatment of cancers. Synergistic effects of catechins when combined with other phytochemicals and drugs, nanostructure- based delivery system, and molecular modifications of EGCG and catechins as means were discussed, and thus provide the basis to better utilize GTCs as the main ingredient of functional foods to reduce the risk of human cancer.

Evaluation inhibitory activity of catechins on trypsin by capillary electrophoresis–based immobilized enzyme microreactor with chromogenic substrate

In this study, a capillary electrophoresis-based online immobilized enzyme microreactor was developed for evaluating the inhibitory activity of green tea catechins and tea polyphenol extracts on trypsin. The immobilized trypsin activity and other kinetic parameters were evaluated by measuring the peak area of the hydrolyzate of chromogenic substrate S-2765. The results indicated that the activity of the immobilized trypsin remained approximately 90.0% of the initial immobilized enzyme activity after 30 runs. The value of Michaelis-Menten constant (Km ) was (0.47 ± 0.08) mM, and the half-maximal inhibitory concentration (IC50 ) and inhibition constant (Ki ) of benzamidine were measured as 3.34 and 3.00mM, respectively. Then, the inhibitory activity of four main catechins (epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate) and three tea polyphenol extracts (green tea, white tea, and black tea) on trypsin were investigated. The results showed that four catechins and three tea polyphenol extracts had potential trypsin inhibitory activity. In addition, molecular docking results illustrated that epigallocatechin gallate, epicatechin gallate, epicatechin, and epigallocatechin were all located not only in the catalytic cavity, but also in the substrate-binding pocket of trypsin. These results indicated that the developed method is an effective tool for evaluating inhibitory activity of catechins on trypsin.

Efficacy of Topical Treatment with (-)-Epigallocatechin Gallate, A Green Tea Catechin, in Mice with Cutaneous Leishmaniasis.

The treatment of leishmaniasis includes pentavalent antimony drugs but, because of the side effects, toxicity and cases of treatment failure or resistance, the search of new antileishmanial compounds are necessary. The aims of this study were to evaluate and compare the in vitro antileishmanial activity of four green tea catechins, and to assess the efficacy of topical (−)-epigallocatechin gallate in a cutaneous leishmaniasis model. The antileishmanial activity of green tea catechins was evaluated against intracellular amastigotes, and cytotoxicity was performed with human monocytic cell line. BALB/c mice were infected in the ear dermis with Leishmania (Leishmania) amazonensis and treated with topical 15% (−)-epigallocatechin gallate, intraperitoneal Glucantime, and control group. The efficacy of treatments was evaluated by quantifying the parasite burden and by measuring the lesions size. (−)-Epigallocatechin gallate and (−)-epigallocatechin were the most active compounds with IC50 values <59.6 µg/mL and with a selectivity index >1. Topical treatment with (−)-epigallocatechin gallate decreased significantly both lesion size and parasite burden (80.4% inhibition) compared to control group (p < 0.05), and moreover (−)-epigallocatechin gallate showed a similar efficacy to Glucantime (85.1% inhibition), the reference drug for leishmaniasis treatment.

Antibacterial green tea catechins from a molecular perspective: mechanisms of action and structure-activity relationships.

This review summarizes the mechanisms of antibacterial action of green tea catechins, discussing the structure-activity relationship (SAR) studies for each mechanism. The antibacterial activity of green tea catechins results from a variety of mechanisms that can be broadly classified into the following groups: (1) inhibition of virulence factors (toxins and extracellular matrix); (2) cell wall and cell membrane disruption; (3) inhibition of intracellular enzymes; (4) oxidative stress; (5) DNA damage; and (6) iron chelation. These mechanisms operate simultaneously with relative importance differing among bacterial strains. In all SAR studies, the highest antibacterial activity is observed for galloylated compounds (EGCG, ECG, and theaflavin digallate). This observation, combined with numerous experimental and theoretical evidence, suggests that catechins share a common binding mode, characterized by the formation of hydrogen bonds and hydrophobic interactions with their target.

Changes in the Biotransformation of Green Tea Catechins Induced by Different Carbon and Nitrogen Sources in Aspergillus niger RAF106.

Biotransformation of green tea catechins mediated by microbes and/or enzymes could increase their bioavailability and improve their health benefits, but the regulatory mechanism remains unclear. Here, Aspergillus niger RAF106 isolated from Pu-erh tea was proved to be capable of degrading gradually ester-catechins into non-ester-catechins with higher bioavailability and gallic acid (GA) in aqueous solution only containing green tea catechins, and the products displayed similar radical-scavenging activity in vitro with the control. Meanwhile, the degradation was mediated by inducible enzymes as the extracellular form, and tannase might be an important enzyme among the extracellular enzymes. Moreover, it was found for the first time that the biotransformation was accelerated significantly by the addition of different nitrogen sources (i.e., yeast extract, peptone, NaNO3, and NH4Cl) and lactose through stimulating the hyphal growth and the tannase activities but was inhibited by glucose effect. Furthermore, nitrogen sources continued to promote the degradation of GA and/or non-ester-catechins by up-regulating the transcriptional expression of two dioxygenases and 10 monooxygenases. Besides, the addition of different nutrient sources except yeast extract did not alter the radical-scavenging activity of green tea catechins during the whole fermentation. These results provide a global insight into the roles of A. niger RAF106 and different nutrient sources in mediating the biotransformation of green tea catechins and modifying the radical-scavenging activity of biotransformed catechins.

Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea.

Anticandidal synergistic activity of green tea catechins, antimycotics and copper sulphate as a mean of combinational drug therapy against candidiasis

The present investigation aims at evaluating synergistic herbal based composition of purified catechins with fluconazole, amphotericin B and copper sulphate against Candida albicans (MTCC 3017) and Candida glabrata (MTCC 3019). The catechins were isolated from green tea leaves of Assam, Himachal Pradesh and Uttarakhand regions of India. The synergistic activity of combinations against Candida species was assessed following microdilution checkerboard technique and time kill assay. The inhibitory action of most significant combination on treated Candida cells was assessed by scanning electron microscopy. Cytotoxicity of synergistic compositions was further analyzed by performing MTT assay on Vero cell lines. Purified catechins of Assam and Himachal Pradesh green tea showed synergistic activity with fluconazole and amphotericin B against Candida species. Time kill assay depicted synergistic activity at minimum inhibitory concentration and twice of minimum inhibitory concentration of purified catechins and antimycotics. Further, Copper sulphate increased anticandidal efficacy of synergistic combinations by 0.4% to 6.63%. SEM analysis revealed morphological distortions of treated Candida cells. Cytotoxicity analysis of synergistic composition depicted high percentage viability (≥91.4% to≥100%) of Vero cell line, which suggests non-cytotoxic activity of proposed composition on healthy cells. It can be inferred that present evaluated synergistic composition can confer promising anticandidal efficacy and requires further investigation of safety and translational guidelines for effective and safer green tea based potent therapeutic drug.

Nanoemulsion based delivery system for improved bioaccessibility and Caco-2 cell monolayer permeability of green tea catechins

The strong antioxidant activities of green tea catechins are shown to exert protective effects against chronic diseases. However, poor chemical stability and low oral bioavailability limits its usage as a potent nutraceutical. Hence, the objective of this study was to investigate the effect of nanoencapsulation on the physicochemical stability, in-vitro bioaccessibility and epithelial permeability of green tea catechins. Soy protein stabilized nanoemulsions containing 0.3 or 0.5 wt% green tea catechins were prepared and stability under different storage conditions (4 ± 1 °C, 28 ± 2 °C, 40 ± 1 °C) was assessed for a period of 15–20 days. At refrigeration temperature, the nanoemulsion containing 10% oil and 0.5% catechins was stable against creaming, phase separation, sedimentation and changes in droplet size, pH and catechin content. There was an observed 2.78 fold increase in the bioaccessibility of major catechins in the nanoemulsified form compared to unencapsulated catechins. Further, there was a significant increase in intestinal permeability of catechins as assessed by Caco-2 cell model. The results indicate the ability of soy protein based nanoemulsions to improve the stability, bioaccessibility and permeability of green tea catechins.

Protective action of green tea catechins in neuronal mitochondria during aging.

Mitochondria are central players in the regulation of cell homeostasis. They are essential for energy production but at the same time, reactive oxygen species accumulate as byproducts of the electron transport chain causing mitochondrial damage. In the central nervous system, senescence and neurodegeneration occur as a consequence of mitochondrial oxidative insults and impaired electron transfer. The accumulation of several oxidation products in neurons during aging prompts the idea that consumption of antioxidant compounds may delay neurodegenerative processes. Tea, one of the most consumed beverages in the world, presents benefits to human health that have been associated to its abundance in polyphenols, mainly catechins, that possess powerful antioxidant properties in vivo and in vitro. In this review, the focus will be placed on the effects of green tea catechins in neuronal mitochondria. Although these compounds reach the brain in small quantities, there are several possible targets, signaling pathways and molecular machinery impinging in the mitochondria that will be highlighted. Accumulated evidence thus far seems to indicate that catechins help prevent neurodegeneration and delay brain function decline.

Identification of green tea catechins as potent inhibitors of the polo-box domain of polo-like kinase 1.

Polo-like kinase 1 (PLK1) plays crucial functions in multiple stages of mitosis and is considered to be a potential drug target for cancer therapy. The functions of PLK1 are mediated by its N-terminal kinase domain and C-terminal polo-box domain (PBD). Most inhibitors targeting the kinase domain of PLK1 have a selectivity issue because of a high degree of structural conservation within kinase domains of all protein kinases. Here, we combined virtual and experimental screenings to identify green tea catechins as potent inhibitors of the PLK1 PBD. Initially, (-)-epigallocatechin, one of the main components of green tea polyphenols, was found to significantly block the binding of fluorescein-labeled phosphopeptide to the PBD at a concentration of 10 μm. Next, additional catechins were evaluated for their dose-dependent inhibition of the PBD and preliminary structure-activity relationships were derived. Cellular analysis further showed that catechins interfere with the proper subcellular localization of PLK1, lead to cell-cycle arrest in the S and G2M phases, and induce growth inhibition of several human cancer cell types, such as breast adenocarcinoma (MCF7), lung adenocarcinoma (A549), and cervical adenocarcinoma (HeLa). Our data provides new insight into understanding the anticancer activities of green tea catechins.

Effects of green tea gargling on the prevention of influenza infection in high school students: a randomized controlled study.

BackgroundThe anti-influenza virus activity of green tea catechins has been demonstrated in experimental studies, but clinical evidence has been inconclusive. School-aged children play an important role in the infection and spread of influenza in the form of school-based outbreaks. Preventing influenza infection among students is essential for reducing the frequency of epidemics and pandemics. As a non-pharmaceutical intervention against infection, gargling is also commonly performed in Asian countries but has not yet been extensively studied.Methods and FindingsA randomized, open label, 2-group parallel study of 757 high school students (15 to 17 years of age) was conducted for 90 days during the influenza epidemic season from December 1st, 2011 to February 28th, 2012, in 6 high schools in Shizuoka Prefecture, Japan. The green tea gargling group gargled 3 times a day with bottled green tea, and the water gargling group did the same with tap water. The water group was restricted from gargling with green tea. The primary outcome measure was the incidence of laboratory-confirmed influenza using immunochromatographic assay for antigen detection. 757 participants were enrolled and 747 participants completed the study (384 in the green tea group and 363 in the water group). Multivariate logistic regression indicated no significant difference in the incidence of laboratory-confirmed influenza between the green tea group (19 participants; 4.9%) and the water group (25 participants; 6.9%) (adjusted OR, 0.69; 95%CI, 0.37 to 1.28; P = 0.24). The main limitation of the study is the adherence rate among high school students was lower than expected.ConclusionsAmong high school students, gargling with green tea three times a day was not significantly more efficacious than gargling with water for the prevention of influenza infection. In order to adequately assess the effectiveness of such gargling, additional large-scale randomized studies are needed.Trial RegistrationClinicalTrials.gov NCT01225770

Quantitative and Qualitative Portrait of Green Tea Catechins (Gtc) Through Hplc

Green tea (Camellia sinensis) is a prosperous source of polyphenols, especially catechins. In the current research, an effort was made to optimize the extraction conditions for maximum yield of catechins from the local green tea Qi-Men. For the purpose, three different solvents were used, i.e., aqueous ethanol (50%), aqueous methanol (50%), and water at different time intervals (20, 40, and 60 min). Green tea catechins were quantified through HPLC using a C18 column and UV detector. The antioxidant activity of green tea catechins was measured through in vitro tests including DPPH radical scavenging ability and antioxidant activity. Results showed that extraction through aqueous ethanol resulted in maximum yield of green tea catechins (17400 ± 0.19 mg/100 g green tea leaves. Moreover, epigallocatechin, epigallocatechin gallate, epicatechin gallate, and epicatechin ranged from 4.26 ± 0.09 to 6.4 ± 0.2, 12.1 ± 0.123 to 17.7 ± 0.3, 1.32 ± 0.03 to 1.81 ± 0.02, 5.48 ± 0.099 to 8.6 ± 0.2 g/100 g of dry-extract, respectively. Furthermore, highest antiradical (80.65 ± 3.69%) and antioxidant activity (67.12 ± 3.08%) were observed in catechins extracted through aqueous ethanol.

Green Tea Catechins: Proposed Mechanisms of Action in Breast Cancer Focusing on the Interplay Between Survival and Apoptosis

Recent data have shown strong chemopreventive and possibly cancer chemotherapeutic effects of green tea polyphenols against cancer. Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly novel treatment strategies are needed for chemoprevention of high risk women and for the treatment of receptor negative breast cancer. Green tea catechins have been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. This review attempts a critical presentation of the mechanisms of action of green tea catechins in breast cancer. Several mechanisms of action of green tea catechins in breast cancer have been proposed including modulation of extracellular signalling, induction of apoptosis through redox regulation, or through modulation of epigenetic alterations. A number of molecular targets of green tea catechins have been suggested i.e molecular chaperones, telomerase, apoptotic cascade. Although the molecular links among the proposed mechanisms of action of green tea catechins are often missing, it must be emphasized that all the proposed mechanisms indicate that green tea catechins inhibit growth and /or promote apoptosis. It would be interesting if future experimental trials could take into account that green tea catechins are multi-target agents and attempt to link every novel proposed target with the other already proposed targets of green tea catechins.

Advances of Green Tea Catechins towards Smart Anticancer Agents

Green tea catechins (GTCs) have shown cancer chemopreventive and chemotherapeutic effects in numerous cell culture systems, animal tumor models, and epidemiologic studies [1,2]. EGCG targets multiple essential survival proteins and pathways in human cancer cells. The anticancer activities of GTCs are believed to be mostly mediated by epigallocatechin-3-O-gallate (EGCG), the most abundant and bioactive compound in green tea [1]. Many researchers have already reported that EGCG or its analogs results in cell cycle arrest and apoptosis of several cancer cells, but not of normal cells [3-8]. However, the underlying mechanism of these differential responses to EGCG in cancer cells versus their normal counterparts is not fully elucidated yet. Even though the selective anticancer mode of action mechanism of EGCG is multifaceted, some of feasible mechanisms, known so far, are as follows:

Antiviral activity of green tea catechins against feline calicivirus as a surrogate for norovirus

In this study, several medicinal plant extracts including spices, herb teas, and medical herbs were screened for antiviral activity against feline calicivirus (FCV), a surrogate of norovirus. Among them, a methanolic extract of green tea, Camellia sinensis, only exhibited a significant antiviral activity against FCV. The methanolic extract was further fractionated with several solvents such as methanol (MeOH), n-hexane, chloroform (CHCl3), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water. EtOAc-soluble fraction exhibited the highest antiviral activity against FCV. Moreover, the analysis of the most active fraction using a HPLC led to the identification of 4 known catechins: (-)-epigallocatechin (EGC), (-)-epicatechin (EC), (-)-epigallocatechin gallate (EGCG), and (-)-epicatechin gallate (ECG). Among the catechins tested in this study, EGCG exhibited the most effective antiviral activity (EC50, 12 mg/mL) with relatively low cytotoxicity (CC50, 320 mg/ mL), resulting relatively high selectivity index value 26.67. To our knowledge, this is the first experimental verification showing antiviral activity of catechins from green tea against FCV.

Highlights of This Issue

Attenuated strains of measles virus are currently assessed in phase I clinical trials as oncolytic viruses able to preferentially infect and kill tumor cells. In addition to the lysis of tumor cells, measles virus vaccine may activate antitumor immune response. To study this phenomenon, Guillerme and colleagues exposed plasmacytoid dendritic cells (pDC), a subset of DC specialized in antiviral immunity, to measles virus vaccine–infected or UV-irradiated tumor cells. Their findings show that only measles virus vaccine–infected cells were able to activate IFN-α production and tumor antigen cross-presentation by pDC. Thus, measles virus vaccine used as an oncolytic virus may recruit pDC in the antitumor immune response.The anticancer activity of green tea catechins has been reported in many laboratory studies and in clinical trials, but the mechanism of action is still unclear. Santilli and colleagues investigated the effect of a clinical grade catechin mixture called Polyphenon E in mouse models of neuroblastoma, a deadly childhood cancer affecting the nervous system. Surprisingly, the differentiation of immunosuppressive myeloid cells and reactivation of the immune system was a key element in the anticancer effect of the catechins. Thus, the nontoxic drug Polyphenon E shows promise as a new therapeutic tool to boost immunologic therapies in children with neuroblastoma.Shin and colleagues examined the underlying molecular mechanism and chemopreventive efficacy of a novel combination of an EGF receptor tyrosine kinase inhibitor with a COX-2 inhibitor, a combination that is being tested in a clinical trial. Preclinical studies confirmed that the combined treatment inhibited growth of head and neck cancer cells with significantly greater potency than either agent alone. Analysis of tissue samples from clinical trial participants consistently showed downregulation of multiple signaling molecules after treatment, which was correlated with clinical response. This investigation of both preclinical studies and the biomarker-driven clinical trial serves as proof-of-principle to justify future chemoprevention trials that target multiple signaling pathways involved in carcinogenesis.Cancer vaccines can be very effective for treating patients, but clinical responses vary widely from one patient to another. Strategies to target treatment to likely responders could significantly improve clinical efficacy, minimize unnecessary side effects, and reduce health care costs. Using a glycan microarray to profile serum antiglycan antibodies, Campbell and colleagues show that prevaccination antibody levels to the blood group A trisaccharide (BG-Atri) are correlated with survival of prostate cancer patients treated with PROSTVAC-VF. Measurement of serum anti-BG-Atri levels prior to vaccination could provide a simple method for preselecting patients who are likely to benefit from PROSTVAC-VF therapy. Additionally, these studies highlight the potential of serum antiglycan antibodies as a convenient reservoir of biomarkers that warrants further investigation.

Cancer Chemoprevention with Green Tea Catechins: From Bench to Bed

Many epidemiological studies and a large number of experimental studies using a variety of animal models have observed that consumption or administration of green tea appears to exert cancer chemopreventive activity. Based on the results of numerous laboratory cell culture investigations, several mechanisms have been hypothesized to underlie the anti-cancer activity of green tea catechins, especially that of (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active constituent in green tea. These mechanisms include promotion of anti-oxidant activity, inhibition of NF-κB and AP-1, regulation of the cell cycle, inhibition of receptor tyrosine kinase pathways, control of epigenetic modifications, and modulation of the immune system. Several recent interventional studies examining the anti-carcinogenic properties of green tea catechins in humans have yielded promising results that suggest the possibility of their application to human clinical trials. This review article analyzes the results of these studies to explicate the effects of consumption or administration of green tea and its constituents on malignancies observed to date and discuss future directions in this research field.

Green and black tea in relation to gynecologic cancers

Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR]=0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR=0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR=0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR=1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.