Effects Of Green Tea Polyphenols Research Articles

Green Tea Polyphenols Inhibit Colorectal Tumorigenesis in Azoxymethane-Treated F344 Rats

ABSTRACTIn studying the cancer-preventive activities of green tea polyphenols, we previously demonstrated that dietary administration of polyphenon E (PPE) inhibited the formation of aberrant crypt foci (ACF) in the colon of azoxymethane (AOM)-treated F344 rats. Herein, we reported cancer-preventive activity of PPE using colorectal cancer as an end point. F344 rats were given two weekly injections of AOM, and then maintained on a 20% high-fat diet with or without 0.24% PPE for 34 wk. In the control group, 83% of rats developed colorectal tumors. Dietary PPE treatment significantly increased the plasma and colonic levels of tea polyphenols, and decreased tumor multiplicity and tumor size. Histological analysis indicated that PPE significantly decreased the incidence of adenocarcinoma, and the multiplicity of adenocarcinoma as well as the multiplicity of adenoma. PPE treatment significantly decreased plasma levels of proinflammatory eicosanoids, prostaglandin E2, and leukotriene B4. It also decreased β-catenin nuclear expression, induced apoptosis, and increased expression levels of RXRα, β, and γ in adenocarcinomas. In conclusion, our results convincingly demonstrated the inhibitory effects of orally administered PPE on colon carcinogenesis in AOM-treated rats and suggested possible biomarkers for the biological effects of green tea polyphenols.

Effect of green tea polyphenol on changes in cancer-related factors in a mouse model of bladder cancer.

329 Background: Many studies have demonstrated the anti-cancer effects of green tea polyphenol (GTP) in a variety of malignancies including bladder cancer, and epidemiologic studies have shown that green tea consumption reduces cancer risk. New cancer treatment strategies in combination with GTP intake have been recommended for several types of cancer. Thus, GTP is thought to be useful not only for cancer prevention but also for treatment. However, the mechanistic basis of these effects is not well understood. Hence, The aims of this study is to clarify the molecular mechanisms of GTP-induced anti-cancer effects, we used a mouse model of chemically induced bladder cancer. Methods: C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14–24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation, and microvessel density were evaluated along with immunohistochemical analysis of human antigen R (HuR), vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Results: Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. In regard to nuclear HuR, its expression was not associated with any parameters, such as carcinogenesis, muscle invasion, and GTP intake. Conclusions: Our results supported the opinion that GTP intake can suppress tumor progression and malignant behavior in animal model of bladder cancer. In addition, we speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer tissue.

Green Tea Polyphenol Epigallocatechin-3-gallate-Alleviated Coxsackievirus B3-induced Myocarditis Through Inhibiting Viral Replication but Not Through Inhibiting Inflammatory Responses.

Viral myocarditis, which is mainly caused by coxsackievirus B3 (CVB3), affects about 5%-20% of the world population and still lacks efficient treatments. Green tea, a tonic and healthful beverage that was originated in ancient China, has been receiving considerable attention for its protective effect on cardiovascular diseases in recent years. In the present investigation, we aimed to explore the effect of green tea polyphenol epigallocatechin-3-gallate (EGCG) on CVB3-induced myocarditis and its underlying mechanism. Our study showed that EGCG could alleviate CVB3-induced myocarditis as evidenced by less cardiac injury and higher survival rate. Furthermore, we found that EGCG failed to downregulate the expression of inflammatory cytokines but could significantly inhibit the replication of CVB3. Furthermore, we found that EGCG treatment could downregulate the protein expression level of coxsackievirus and adenovirus receptor, the major receptor for CVB3 to infect cardiac myocytes. In conclusion, our data indicated that EGCG could ameliorate CVB3-induced myocarditis through inhibiting viral replication, which might provide a potential novel therapeutic strategy for viral myocarditis.

Protective Effects of Green Tea Polyphenol Against Renal Injury Through ROS-Mediated JNK-MAPK Pathway in Lead Exposed Rats.

To investigate the potential therapeutic effects of polyphenols in treating Pb induced renal dysfunction and intoxication and to explore the detailed underlying mechanisms. Wistar rats were divided into four groups: control groups (CT), Pb exposure groups (Pb), Pb plus Polyphenols groups (Pb+PP) and Polyphenols groups (PP). Animals were kept for 60 days and sacrificed for tests of urea, serum blood urea nitrogen (BUN) and creatinine. Histological evaluations were then performed. In vitro studies were performed using primary kidney mesangial cells to reveal detailed mechanisms. Cell counting kit-8 (CCK-8) was used to evaluate cell viability. Pb induced cell apoptosis was measured by flow cytometry. Reactive oxygen species (ROS) generation and scavenging were tested by DCFH-DA. Expression level of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1-β) and IL-6 were assayed by ELISA. Western blot and qPCR were used to measure the expression of ERK1/2, JNK1/2 and p38. Polyphenols have obvious protective effects on Pb induced renal dysfunction and intoxication both in vivo and in vitro. Polyphenols reduced Pb concentration and accumulation in kidney. Polyphenols also protected kidney mesangial cells from Pb induced apoptosis. Polyphenols scavenged Pb induced ROS generation and suppressed ROS-mediated ERK/JNK/p38 pathway. Downstream pro-inflammatory cytokines were inhibited in consistency. Polyphenol is protective in Pb induced renal intoxication and inflammatory responses. The underlying mechanisms lie on the antioxidant activity and ROS scavenging activity of polyphenols.

고지방식이와 저용량 스트렙토조토신으로 유도된 2형 당뇨병 흰쥐에서 녹차 폴리페놀과 비타민 C 병합 투여 효과

녹차 폴리페놀과 비타민 C가 2형 당뇨병에 미치는 영향을 관찰하기 위해 고지방식이와 저용량 스트렙토조토신을 이용하여 당뇨병이 유도된 흰쥐에 polyphenon 60(P60)과 sodium ascorbate(SA)를 16주간 투여한 후 공복 혈당, 혈장 인슐린, 혈청 중성지질, BUN 및 creatinine과 신장 GGT와 AP 활성도를 측정하였다. 당뇨병 흰쥐에 P60이나 SA투여로 인한 식이섭취량과 체중의 변화는 없었다. 공복 혈당은 당뇨 대조군(DC 군)에서 대조군(NC 군)의 5배로 증가하였으며, 당뇨+녹차 폴리페놀(DM+P60) 군은 14%, 당뇨+녹차 폴리페놀+비타민 C(DM+P60+SA) 군은 28%가 DC군보다 감소하였고, 당뇨+비타민 C(DM+SA) 군은 DC 군과 유의한 차이가 없었다. 혈장 인슐린 양은 각 실험군 사이에 유의한 차이가 없으며, 인슐린 저항성 지수 HOMA-IR은 DC 군에서 증가하였고 DM+P60+SA 군은 DC 군보다 감소하였다. 혈청 creatinine 양은 DC 군에서 증가하였고 DM+P60 군은 DC 군보다 17% 감소하였으며, DM+P60+SA 군은 DC 군보다 43% 감소하였다. 혈청 BUN 양은 DC 군에서 증가하였고 DM+P60+SA 군은 DC 군보다 41% 감소하였다. 신장 GGT와 AP 활성도는 DC 군에서 감소하였고 DM+P60+SA 군은 DC 군보다 감소가 적었으며, DM+SA군은 DC 군과 유의한 차이가 없었다. 이상의 실험 결과 2형당뇨병에서 녹차 폴리페놀과 비타민 C 복합 투여가 혈당, 인슐린 저항성 및 혈청 중성지질량 개선 및 신장 손상 방지효과가 녹차 폴리페놀이나 비타민 C를 단독으로 투여하였을 때보다 더 증가함을 확인할 수 있었다. 녹차 폴리페놀과 비타민 C의 혈당 상승 억제와 신장 손상 방지 효과에 대한 계속된 연구가 필요하며, 녹차 폴리페놀과 비타민 C는 당뇨병 환자에게 혈당을 조절하고 신장 손상을 방지하는 기능성식품 제재로서 개발 가능성이 있는 것으로 생각한다.

The effect of green tea polyphenols on gut microbial diversity and fat deposition in C57BL/6J HFA mice.

Quantitative and qualitative changes in gut microbial composition have been linked to obesity and obesity-related complications, and eating pattern has been shown to significantly impact the gut microbiome. Meanwhile, tea polyphenols are known to have health benefits such as improving glucose tolerance and decreasing liver fat deposition that may be helpful in combating obesity and obesity-related disorders. We therefore studied the effect of green tea polyphenols on gut microbial diversity and fat deposition in C57BL/6J Human Flora-Associated (HFA) mice, which were divided into five groups: low fat (LF), high fat (HF), high fat + 0.05% tea polyphenols (HF + 0.05% TP), high fat + 0.2% tea polyphenols (HF + 0.2% TP) and high fat + 0.8% tea polyphenols (HF + 0.8% TP). 16S rRNA V6-V8 region PCR-DGGE profiles showed that a high fat diet was associated with a significant reduction in microbial diversity. This reduction could be alleviated by a HF + 0.2% TP diet, with a significant increase in the number of lactic acid bacteria in the HF + 0.2% TP group compared with the LF group (P < 0.05). Body weight (P < 0.05) and fat pad weight (P < 0.001) were significantly increased in the HF compared with the LF group, with notable adipocyte hypertrophy in the HF group, indicating successful establishment of the high fat model. Body weight among the HF + 0.2% TP group and HF + 0.8% TP group (but not the HF + 0.05% TP group) was significantly lower than the body weight in the HF group (P < 0.01). Therefore, tea polyphenols may effectively retard diet-induced weight gain and body fat gain, adipocyte hypertrophy and hepatic steatosis in a dose-dependent manner.

Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons.

Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

The benefits of respective and combined use of green tea polyphenols and ERK inhibitor on the survival and neurologic outcomes in cardiac arrest rats induced by ventricular fibrillation

BackgroundCerebral injury is a main factor contributing to a high mortality after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). ObjectiveWe sought to evaluate the effect of green tea polyphenols (GTPs) and ERK1/2 inhibitor PD98059 (PD) on the survival and neurologic outcomes after CA/CPR in rats. MethodsFirst, rats were subjected to CA after CPR. The rats that restored spontaneous circulation were blindly allocated to the saline group (saline, IV, n = 12), the GTP group (GTPs, 10 mg/kg, IV, n = 12), the PD group (PD, 0.3 mg/kg, IV, n = 12), and the GTPs + PD group (GTPs, 10 mg/kg; PD, 0.3 mg/kg, IV, n = 12). Another 12 rats without experiencing CA and CPR were served as a sham group. Survival and the neurologic deficit score were observed for 72 hours after restoration of spontaneous circulation. Second, same experimental procedures were performed, and in 1 of 5 groups, animals were divided into 4 subgroups further according to the different time points (12, 24, 48, and 72 hours after restoration of spontaneous circulation [ROSC], n = 6/group). Brain tissues were harvested at relative time points for the morphologic evaluation as well as reactive oxygen species (ROS), malonylaldehyde, and superoxide dismutase (SOD) measurement. ResultsGreen tea polyphenols, PD, and a combination of GTPs and PD used after ROSC alleviated the morphologic changes of the cerebrum. These 3 treatments also decreased the productions of ROS and malonylaldehyde, increased SOD activities in cerebral tissues, and improved the neurologic deficit and survival rates at 12, 24, 48, and 72 hours after ROSC. ConclusionsAdministration of GTPs and PD after ROSC can alleviate cerebral injury, improve the survival and neurologic outcomes via reduction of ROS, and increase of SOD activity in a rat CA/CPR model.

Green tea supplementation benefits body composition and improves bone properties in obese female rats fed with high-fat diet and caloric restricted diet

This study investigated the effects of green tea polyphenols (GTP) supplementation on body composition, bone properties, and serum markers in obese rats fed a high-fat diet (HFD) or a caloric restricted diet (CRD). Forty-eight female rats were fed an HFD ad libitum for 4 months, and then either continued on the HFD or the CRD with or without 0.5% GTP in water. Body composition, bone efficacy, and serum markers were measured. We hypothesized that GTP supplementation would improve body composition, mitigate bone loss, and restore bone microstructure in obese animals fed either HFD or CRD. CRD lowered percent fat mass; bone mass and trabecular number of tibia, femur and lumbar vertebrae; femoral strength; trabecular and cortical thickness of tibia; insulin-like growth factor-I and leptin. CRD also increased percent fat-free mass; trabecular separation of tibia and femur; eroded surface of tibia; bone formation rate and erosion rate at tibia shaft; and adiponectin. GTP supplementation increased femoral mass and strength (P = .026), trabecular thickness (P = .012) and number (P = .019), and cortical thickness of tibia (P < .001), and decreased trabecular separation (P = .021), formation rate (P < .001), and eroded surface (P < .001) at proximal tibia, and insulin-like growth factor-I and leptin. There were significant interactions (diet type × GTP) on osteoblast surface/bone surface, mineral apposition rate at periosteal and endocortical bones, periosteal bone formation rate, and trabecular thickness at femur and lumbar vertebrate (P < .05). This study demonstrates that GTP supplementation for 4 months benefited body composition and improved bone microstructure and strength in obese rats fed with HFD or HFD followed by CRD diet.

Green tea extract and its major constituent epigallocatechin-3-gallate inhibit growth and halitosis-related properties of Solobacterium moorei.

BackgroundSolobacterium moorei is a volatile sulfide compound (VSC)-producing Gram-positive anaerobic bacterium that has been associated with halitosis. The aim of this study was to investigate the effects of green tea extract and its major constituent epigallocatechin-3-gallate (EGCG) on growth and several halitosis-related properties of S. moorei.MethodsA microplate dilution assay was used to determine the antibacterial activity of green tea extract and EGCG against S. moorei. Their effects on bacterial cell membrane integrity were investigated by transmission electron microscopy and a fluorescence-based permeability assay. Biofilm formation was quantified by crystal violet staining. Adhesion of FITC-labeled S. moorei to oral epithelial cells was monitored by fluorometry. The modulation of β-galactosidase gene expression in S. moorei was evaluated by quantitative RT-PCR.ResultsThe green tea extract as well as EGCG inhibited the growth of S. moorei, with MIC values of 500 and 250 μg/ml, respectively. Transmission electron microscopy analysis and a permeabilization assay brought evidence that the bacterial cell membrane was the target of green tea polyphenols. Regarding the effects of green tea polyphenols on the S. moorei colonization properties, it was found that biofilm formation on EGCG-treated surfaces was significantly affected, and that green tea extract and EGCG can cause the eradication of pre-formed S. moorei biofilms. Moreover, both the green tea extract and EGCG were found to reduce the adherence of S. moorei to oral epithelial cells. The β-galactosidase activity of S. moorei, which plays a key role in VSC production, was dose-dependently inhibited by green tea polyphenols. In addition, EGCG at ½ MIC significantly decreased the β-galactosidase gene expression.ConclusionOur study brought evidence to support that green tea polyphenols possess a number of properties that may contribute to reduce S. moorei-related halitosis. Therefore, these natural compounds may be of interest to be used to supplement oral healthcare products.

Protective effects of green tea polyphenols against benzo[a]pyrene-induced reproductive and trans-generational toxic effects in Japanese Medaka (Oryzias latipes)

In order to investigate the protective effect of green tea polyphenols (GTP) on benzo[a]pyrene (BaP)-induced reproductive and trans-generational toxicity, Japanese Medaka was injected intraperitoneally with BaP alone and co-injected with both BaP and GTP of different concentrations, respectively. Exposure to BaP alone significantly suppressed fecundity, fertilization success, and egg diameter/protein content and markedly induced deformation ratio in F1 generation. However, GTP could help recover reproductive functions, egg quality suppressed by BaP and reduced deformation ratio. VTG-1, a molecular marker of reproductive toxicity, was significantly down-regulated in females exposed to BaP, but a dose-dependent increase was observed in co-exposed groups. Up-regulation of GSH-Px, dose-dependent decrease of CYP1A1, and the GST expression inhibited by BaP was recovered and even markedly up-regulated in the co-exposure groups. These findings show promising protective effects of GTP against BaP-induced reproductive and trans-generational toxicity.

Effects of dietary supplementation with green tea polyphenols on digestion and meat quality in lambs infected with Haemonchus contortus

Ujumqin sheep are susceptible to infection by the gastrointestinal nematode Haemonchus contortus, which reduces productivity and total meat yield in sheep. Thus, the effects of green tea polyphenol (GTP) supplements (0, 2, 4, or 6g of GTP/kg feed) on dietary nutrient digestibility and meat quality in lambs infected with H. contortus were examined; control lambs were not infected. H. contortus infections did not affect digestion but the apparent digestibilities of nutrients were decreased by dietary 2g of GTP/kg feed supplementation. There was an interaction between treatment and sampling time on plasma total protein, urea nitrogen, and amino acid concentrations. The antioxidant activity and meat color of INFGTP0 lambs decreased. In conclusion, H. contortus infections in lambs decreased meat quality, but appropriate levels of dietary GTP supplementation diminished these negative effects though lower dose of GTP supplement showed negative effects on digestion.

Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage.

Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an in vitro model. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53).

Epigenetic Regulation by Dietary Phytochemicals in Photocarcinogenesis

Epigenetic mechanisms are of interest as therapeutic targets in photocarcinogenesis as they are reversible. Evidence derived from mouse models of ultraviolet radiation-induced skin carcinogenesis and other photocarcinogenesis models suggests that these changes can be controlled or prevented by phytochemicals derived from dietary plants. Thus, improved knowledge of the potential effects of green tea polyphenols (GTPs) and proanthocyanidins from grape seeds (GSPs) on epigenetic processes may be useful for the chemoprevention of skin cancers which are a major public health concern. In the present article, we provide a short review of epigenetic regulatory mechanisms in mammals and examine the impact of two natural substances, GTPs, and GSPs, on these epigenetic processes.

Abstract 1242: Green tea polyphenols inhibit the growth and induce death of melanoma cells by initiating DNA damage and inhibition of class I histone deacetylases

Abstract Melanoma remains a leading cause of death from skin diseases due to its propensity to metastasis, and is increasing rapidly in children. Although, melanoma is less common than other types of skin cancers, however, it causes the majority (75%) of skin cancer-related deaths. The average survival of patients with advanced stage of melanoma is less than a year because no effective strategies are available for metastatic melanoma. Since melanoma is a highly malignant cancer, an approach that can inhibit its growth and progression may facilitate the development of an effective strategy for its treatment or prevention. As green tea polyphenols (GTPs) have been shown to have anti-skin carcinogenic effects, we have examined the chemotherapeutic effect of GTPs on the growth of different melanoma cell lines and the molecular mechanisms underlying these effects using an in vitro model. Treatment of melanoma cells (A375 and Hs294t) with GTPs (0, 20, 40 and 60 µg/ml) for 24 and 48 h significantly inhibited histone deacetylase (HDAC) activity, reduced the levels of class 1 HDAC proteins (HDAC 1, 2, 3 and 8) and enhanced histone acetyltransferase (HAT) activity in a dose-dependent manner. These effects of GTPs on melanoma cells were associated with DNA damage, which was evident by Comet assay, and significant reduction in the viability of melanoma cells and induction of cell death. Concomitant treatment of melanoma cells with a proteasome inhibitor, MG132, prevented GTPs-induced degradation of class I HDACs, suggesting that GTPs reduced the levels of HDAC proteins in melanoma cells through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells (A375 and Hs294t). Treatment of A375 and Hs294t cells with GTPs resulted in an alteration of cell cycle regulatory proteins of G0/G1 phase, and that is a decrease in the levels of cyclin D1, D2 and E, and cyclin dependent kinases, CDK2, CDK4 and CDK6 in a dose-dependent manner. Simultaneously, it was also observed that the levels of p21 and p53 proteins were also increased in the cells after the treatment with GTPs, which may have a role in G0/G1 phase arrest and DNA damage. Together, our study provides new insights into the role of class I HDACs in the chemotherapeutic effects of green tea polyphenols on melanoma cells. Citation Format: Ram Prasad, Santosh K. Katiyar. Green tea polyphenols inhibit the growth and induce death of melanoma cells by initiating DNA damage and inhibition of class I histone deacetylases. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1242. doi:10.1158/1538-7445.AM2014-1242

Effect of green tea consumption on blood pressure: A meta-analysis of 13 randomized controlled trials

The studies investigating the effects of green tea on blood pressure (BP) have generated inconsistent results. The aim of this study is to quantitatively evaluate the effects of green tea on BP control. PubMed, Embase, and the Cochrane Library (updated to March 2014) were searched for randomized controlled trials evaluating the effects of green tea on BP. Pooled effect of green tea consumption on BP was evaluated using fixed-effects or random-effects model. Thirteen trials comprising a total of 1,367 subjects were included in the current meta-analysis. The overall outcome of the meta-analysis suggested that green tea consumption significantly decrease systolic blood pressure (SBP) level by −1.98 mmHg (95% CI: −2.94, −1.01 mmHg; P < 0.001). Compared with the control group, green tea also showed a significant lowering effect on diastolic blood pressure (DBP) in treatment group (−1.92 mmHg; 95% CI: −3.17, −0.68 mmHg; P = 0.002). Subgroup analyses further suggested that the positive effect of green tea polyphenols on BP was only showed in studies using a low-dose green tea polyphenol, with the long-term intervention duration or ruling out the confounding effects of caffeine. The meta-analysis suggested that green tea consumption had a favorable effect on decrease of BP.

Excellent anti-proliferative and pro-apoptotic effects of (−)-epigallocatechin-3-gallate encapsulated in chitosan nanoparticles on human melanoma cell growth both in vitro and in vivo

Earlier we demonstrated the anti-proliferative and pro-apoptotic effects of green tea polyphenol epigallocatechin-3-gallate (EGCG) on human melanoma cells (Int J Cancer. 2005; 114(4): 513-21). The doses used in this study were not physiologically attainable and for chemoprevention the preferred route of administration is oral consumption. To overcome these shortcomings, and taking advantage of our novel concept of nanochemoprevention (Cancer Res. 2009;69(5):1712-6), we developed a nanotechnology based oral delivery system to encapsulate EGCG. Here, using human melanoma Mel 928 cells we demonstrate 8-fold dose advantage of this nanoformulation over native EGCG. Further, nano-EGCG treated cells showed marked induction of apoptosis and cell cycle inhibition along with the growth of Mel 928 tumor xenograft. Nano-EGCG also inhibited proliferation (Ki-67 and PCNA) and induced apoptosis (Bax, PARP) in tumors harvested from the treated mice. These observations warrant further in vivo efficacy studies of nano-EGCG in robust animal models of human melanoma. From the Clinical EditorThis team of investigators developed a nanotechnology based oral delivery system to encapsulate EGCG, a green tea-derived polyphenol in chitosan nanoparticles. Using human melanoma cells, an eight-fold dose advantage was demonstrated over native EGCG, leading to measurable apoptosis induction and proliferation inhibition, warranting further in vivo investigations.

Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway

BackgroundHyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway.MethodsMale Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2′, 7′-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot.ResultsHF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG.ConclusionsGTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.

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.

유방암 세포(EMT6) 이식 마우스에서 녹차폴리페놀 음용이 시스플라틴의 암 조직 성장 억제에 미치는 영향

본 연구는 녹차폴리페놀이 시스플라틴의 항암작용과 신장독성에 미치는 영향을 유방암 세포(EMT6)와 암세포 이식 마우스를 이용하여 in vitro와 in vivo 실험으로 관찰하였다. 배양한 EMT6 세포에서 녹차폴리페놀은 시스플라틴에 의한 세포 독성을 증가시켰다. 마우스에 EMT6 세포를 주사하여 유발된 종양의 크기가 시스플라틴군(CP)보다 시스플라틴＋녹차폴리페놀군(CP＋GTP)에서 유의하게 작았고, 종양조직 p53와 caspase-3 활성화가 시스플라틴군(CP)보다 시스플라틴＋녹차폴리페놀군(CP＋GTP)에서 유의하게 높았으며, 신장 GGT와 AP 활성은 시스플라틴군(CP)보다 시스플라틴＋녹차폴리페놀군(CP＋GTP)에서 유의하게 높았고, 신장 조직학적 소견에서 신세뇨관 확장과 괴사가 시스플라틴군(CP)보다 시스플라틴＋녹차폴리페놀군(CP＋GTP)에서 유의하게 낮았다. 이상의 결과 녹차폴리페놀은 EMT6 유방암 세포를 이용한 in vitro 및 in vivo 실험에서 시스플라틴의 항암작용을 증강시키면서 신장에 대한 독성 부작용은 감소시키는 효과가 있는 것으로 추측된다. 녹차폴리페놀의 시스플라틴 항암작용 증강과 신장 독성 억제 및 감소 효과는 시스플라틴에 의한 암 치료 시 화학요법제의 보조제로서 이용가치가 있는 것으로 생각되며, 항암화학요법제에 대한 보조제로의 개발을 위해서는 대규모 동물실험을 통한 효과 입증 및 부작용에 대한 실험과 임상연구가 뒷받침되어야 할 것으로 사료된다.