Activity Of Green Tea Polyphenols Research Articles

Encapsulating Epigallocatechin-3-Gallate (EGCG) in Chitosan Nanoparticles Influenced Multiple Genes Controlling Oncostatic Signaling Pathways in HepG2 Cells

The primary polyphenol in green tea, epigallocatechin-3-gallate (EGCG), is the primary active polyphenol in green tea that showed a remarkable anticancer effect in a variety of cancer types including liver cancer. However, its anticancer impact on gene expressions related to liver cancer proliferation and apoptosis is limited. The current study investigated the oncostatic influence of chitosan encapsulating EGCG (Chit-nanoEGCG) on human hepatocellular carcinoma HepG2 cells compared with its native form and the conventional anticancer drug cisplatin in vitro. The Chit-nanoEGCG caused a dose-dependent decrease in cell viability and significantly induced apoptosis compared with control. Flow cytometric analysis confirmed the results of RT-qPCR, displaying a significant increase in the expression of transcriptomes (P53, Bax, Caspase-3, Caspase-9, and PARP) with a significant decrease in the antiapoptotic Bcl-2 gene. Also, there was a significant decrease in transcription genes (OCT4 and SOX2) and receptor genes (CD133, NOTCH1, c-MET, and Ezrin) but an increase in CD95 expression. Furthermore, there was a highly significant decrease in oncogenes (mTOR, PI3K, RALA, and BMI) in HepG2 cells after Chit-nanoEGCG treatment when compared with the control group. The current findings indicate that Chit-nanoEGCG had a significant impact on a number of genes involved in controlling signaling pathways to inhibit the proliferation and development of HepG2 cells. In addition, encapsulating EGCG in chitosan nanoparticles increases its antitumor effectiveness compared to its native form, which encourages the use of various polyphenols in nanochemotherapy for cancer treatment. The finding that the nanoparticles (NPs) influenced the expression of genes involved in apoptosis and proliferation enables the development of medical chemotherapeutic agent for the treatment of hepatocellular carcinoma.Graphical

Mechanism of the combined action of green tea polyphenols and concurrent radiochemotherapy in regulating GSK-3β to treat non-small cell lung cancer through the Wnt∕β-catenin pathway.

Green tea, derived from Camellia sinensis, contains polyphenolic active compounds that exhibit diverse pharmacological effects including anticancer, anti-inflammatory, antioxidant, and immunomodulatory properties. Employing various concentrations of green tea polyphenols (GTPs; 0, 100, 200, 300, 400, 500 μg∕mL), human normal lung epithelial cells (BEAS-2B) and non-small cell lung cancer (NSCLC) cells (A549) underwent treatment. The cell viability was assessed using the cell counting kit-8 (CCK-8) assay, proliferation was examined through the colony formation assay, apoptosis was monitored via flow cytometry, cell migration, and epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin) were determined by Western blot. A549 cells were subjected to Cisplatin (0, 0.5, 1, 1.5 μM) and X-ray irradiation (0, 2, 4, 6 Gy) for treatment to probe the influence of GTPs on A549 cells in response to chemoradiotherapy. The functioning mechanism of GTPs in the context of NSCLC was validated using lithium chloride (LiCl) [a glycogen synthase kinase-3 beta (GSK-3β) inhibitor], which activates the Wnt∕β-catenin pathway. GTPs suppressed NSCLC cell viability in a concentration-dependent pattern, with a half-maximal inhibitory concentration (IC50) of 362.5 μg∕mL, while showing little impact on BEAS-2B cells' viability (at concentrations not exceeding 500 μg∕mL). Treatment with GTPs dampened colony formation of NSCLC cells, while promoting apoptosis. LiCl treatment vigorously attenuated the inhibitory impact of GTPs on the malignant phenotype of NSCLC cells. Mechanistic studies suggested that GTPs strengthened GSK-3β stability, thereby impeding the Wnt∕β-catenin pathway. Tea polyphenols (TPs) in conjunction with concurrent radiochemotherapy (CRCT) enhance the stability of GSK-3β and dampen the Wnt∕β-catenin pathway, hence exerting anticancer effects in NSCLC.

Transcriptomic, 16S ribosomal ribonucleic acid and network pharmacology analyses shed light on the anticoccidial mechanism of green tea polyphenols against Eimeria tenella infection in Wuliangshan black-boned chickens

BackgroundEimeria tenella is an obligate intracellular parasitic protozoan that invades the chicken cecum and causes coccidiosis, which induces acute lesions and weight loss. Elucidating the anticoccidial mechanism of action of green tea polyphenols could aid the development of anticoccidial drugs and resolve the problem of drug resistance in E. tenella.MethodsWe constructed a model of E. tenella infection in Wuliangshan black-boned chickens, an indigenous breed of Yunnan Province, China, to study the efficacy of green tea polyphenols against the infection. Alterations in gene expression and in the microbial flora in the cecum were analyzed by ribonucleic acid (RNA) sequencing and 16S ribosomal RNA (rRNA) sequencing. Quantitative real-time polymerase chain reaction was used to verify the host gene expression data obtained by RNA sequencing. Network pharmacology and molecular docking were used to clarify the interactions between the component green tea polyphenols and the targeted proteins; potential anticoccidial herbs were also analyzed.ResultsTreatment with the green tea polyphenols led to a reduction in the lesion score and weight loss of the chickens induced by E. tenella infection. The expression of matrix metalloproteinase 7 (MMP7), MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2 was significantly altered in the E. tenella infection plus green tea polyphenol-treated group and in the E. tenella infection group compared with the control group; these genes were also predicted targets of tea polyphenols. Furthermore, the tea polyphenol (-)-epigallocatechin gallate acted on most of the targets, and the molecular docking analysis showed that it has good affinity with interferon induced with helicase C domain 1 protein. 16S ribosomal RNA sequencing showed that the green tea polyphenols had a regulatory effect on changes in the fecal microbiota induced by E. tenella infection. In total, 171 herbs were predicted to act on two or three targets in MMP7, MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2.ConclusionsGreen tea polyphenols can directly or indirectly regulate host gene expression and alter the growth of microbiota. The results presented here shed light on the mechanism of action of green tea polyphenols against E. tenella infection in chickens, and have implications for the development of novel anticoccidial products.Graphical

In Vitro Antithrombotic, Antitumor and Antiangiogenic Activities of Green Tea Polyphenols and Its Main Constituent Epigallocatechin-3-gallate

The balance between embolic risk and bleeding represents a clinical challenge in cancer patient treatment, encouraging studies on adjuvant oncologic treatments. Thereby, this study evaluated the in vitro effect of green tea extract (GTE) and epigallocatechin-3-gallate (EGCG) on hemostasis modulation and the antineoplastic effect on melanoma cells (B16-F10) by applying platelet aggregation, angiogenesis and viability cell assays. The results displayed a significant platelet antiaggregant effect, corresponding to 50 and 80% for the extract and EGCG, respectively, compared to the negative control. Furthermore, both GTE and EGCG exhibited antitumor effects by reducing melanoma cell growth by 25 and 50%, respectively, verified by cellular apoptosis. Regarding angiogenesis, these substances inhibited blood vessel formation, reaching about 25% and 99% for GTE and EGCG at 100 μg/mL, respectively. Moreover, TNF-α cell stimulation evidenced VEGF and IL-8 secretion inhibition at 55 and 20% with GTE, while EGCG promoted an inhibition around 78% for both VEGF and IL-8. The results indicate the promising performance of GTE and EGCG as an option for treating cancer and its side effects. Nonetheless, further studies are required to elucidate their action mechanism on clotting, cell death and angiogenesis.

Regulatory Effects and Mechanism of Action of Green Tea Polyphenols on Osteogenesis and Adipogenesis in Human Adipose Tissue-Derived Stem Cells.

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O staining and triglycerides synthesis measurement. Osteoporosis of hADSC was measured using alkaline phosphatase assays and intracellular calcium levels. Immunofluorescence staining and qRT-PCR were used to detect PPARγ-CEBPA regulated adipogenic pathway regulated by PPAR-CEBPA and the osteogenic pathway mediated by RUNX2-BMP2. We found that GTPs treatment significantly decreased lipid accumulation and cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTPs downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated-Cebpa expression. GTPs treatment significantly enhanced hADSCs differentiation into osteoblasts compared to control and pioglitazone-treated cells. GTPs upregulated RunX2 and Bmp2 proteins and mRNA expression compared to control and significantly attenuated decreased RunX2 and Bmp2 mRNA expression by pioglitazone. In conclusion, our data demonstrates GTPs possesses great ability to facilitate osteogenesis and simultaneously inhibits hADSC differentiation into adipogenic lineage by upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. These findings highlight GTPs' potential to combat osteoporosis associated with obesity.

Antimicrobial Activity of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) against Clinical Isolates of Multidrug-Resistant Vibrio cholerae.

The spread of multidrug-resistant (MDR) Vibrio cholerae necessitates the development of novel prevention and treatment strategies. This study aims to evaluate the in vitro antibacterial activity of green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) against MDR V. cholerae. First, MIC and MBC values were evaluated by broth microdilution techniques against 45 V. cholerae strains. The checkerboard assay was then used to determine the synergistic effect of EGCG and tetracycline. The pharmaceutical mode of action of EGCG was clarified by time-killing kinetics and membrane disruption assay. Our results revealed that all of the 45 clinical isolates were susceptible to EGCG, with MIC and MBC values in the range of 62.5–250 µg/mL and 125–500 µg/mL, respectively. Furthermore, the combination of EGCG and tetracycline was greater than either treatment alone, with a fractional inhibitory concentration index (FICI) of 0.009 and 0.018 in the O1 and O139 representative serotypes, respectively. Time-killing kinetics analysis suggested that EGCG had bactericidal activity for MDR V. cholerae after exposure to at least 62.5 µg/mL EGCG within 1 h. The mode of action of EGCG might be associated with membrane disrupting permeability, as confirmed by scanning electron microscopy. This is the first indication that EGCG is a viable anti-MDR V. cholerae treatment.

Cancer preventive activities of tea polyphenols

The cancer preventive activities of tea (Camellia Sinensis Theaceae) have been investigated extensively. Green tea polyphenols have been shown to inhibit tumorigenesis in different animal models, including those for cancers of the lung, oral cavity, esophagus, stomach, small intestine, colon, bladder, liver, pancreas, skin, prostate and mammary glands. Enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis have been shown to be associated with the inhibition of carcinogenesis by tea polyphenols in animals. Many studies in cell lines have demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. The cancer preventive activity of green tea in humans, however, has not been conclusively demonstrated in epidemiological studies. The relationship between tea consumption and cancer risk may become more clear if we could better quantify the tea consumption, adjust for confounding factors and consider genetic polymorphisms of the population. Ongoing human studies on the prevention of prostate, oral, lung, colon, and breast cancers by tea polyphenols are expected to yield more information on this important topic.

Epigallocatechin-3-gallate in functional food development: From concept to reality

BackgroundEpigallocatechin-3-gallate (EGCG) is the most abundant and pharmaceutically active polyphenol in green tea. It shows diverse health-promoting effects, but due to its low oral bioavailability, its use in functional food development has been impeded. Over the years, the health-promoting effects of EGCG have been extensively reviewed; however, discussions of the possible use of EGCG in food development have been scant, even though copious ready-to-drink green tea beverages and nutritional supplements are available in the market. Scope and approachThe hopes and hypes involved in the use of EGCG in functional food development will be explored based on recent studies. Implications for future efforts to manipulate the properties of EGCG for food applications will be presented. Key findings and conclusionsRecent advances in technologies for structural modification and therapeutics delivery may enhance the food applications of EGCG. Despite this, justifications on the use of EGCG in functional food development should be seriously evaluated until a consensus is reached in terms of the safety and efficiency.

Epigallocatechin Gallate Induces Upregulation of LDL Receptor via the 67kDa Laminin Receptor-Independent Pathway in HepG2 Cells.

Epigallocatechin gallate (EGCG), an active polyphenol in green tea, exhibits various physiological effects, including activation of low-density lipoprotein receptors (LDLR). The previous studies have suggested that EGCG activates LDLR via extracellular signal-regulated kinase (ERK) pathway in HepG2 cells. However, the detailed molecular mechanism remains unclear. Recently, 67kDa laminin receptor (67LR) is identified as a receptor for EGCG. Therefore, this study aims to determine whether 67LR is involved in the mechanism of LDLR activation by EGCG. EGCG induces upregulation of LDLR when 67LR is knocked down in HepG2 cells. Similar effect is observed after the cells are treated with 67LR monoclonal antibody. The loss of antiallergic effect following 67LR siRNA knockdown and 67LR antibody treatment confirms the results since the antiallergic effect of EGCG is known to be mediated by 67LR. EGCG activates LDLR expression via 67LR-independent pathway in HepG2 cells.

Influence of green tea constituents on cultured porcine luteinized granulosa cell functions

The aim of the study was to examine the action of green tea polyphenols (GTPP) and their main constituent, epigallocatechin-3-gallate (EGCG), on porcine ovarian granulosa cells. For this purpose, the effect of GTPP and EGCG on cultured porcine ovarian granulosa cell functions, including proliferation, apoptosis, steroidogenesis and response to insulin-like growth factor I (IGF-I) was examined. Proliferation (the accumulation of proliferating cell nuclear antigen (PCNA) and cyclin B1), apoptosis (the accumulation of bax and caspase 3) and the release of steroid hormones (progesterone and testosterone) were evaluated by using immunocytochemistry and enzyme immunoassay. The addition of both GTPP and EGCG reduced the percentage of both PCNA- and cyclin B1-positive cells, increased the proportion of cells containing bax and caspase 3 and stimulated progesterone release. GTPP had a biphasic effect on testosterone output – stimulating at dose 1 μg/ml and inhibiting at doses 10 and 100 μg/ml, whilst EGCG did not affect testosterone secretion. IGF-I, when administered alone, promoted % of cells containing PCNA, suppressed bax accumulation, and stimulated progesterone release (only at dose 100 ng/ml). Testosterone release increased after the addition of IGF-I at 1 ng/ml, but decreased after IGF-I addition at 10 or 100 ng/ml. Both GTPP and EGCG suppressed or even reversed the effects of IGF-I on percentage of PCNA-positive cells, bax, testosterone output, and promoted IGF-I action on progesterone release. These observations suggested the inhibitory actions of green tea constituents on porcine ovarian granulosa cell functions were mediated through various regulatory mechanisms: suppression of the ovarian cell cycle in the S and G2 phases; promotion of cytoplasmic apoptosis; alteration of steroid hormone release; and, predominantly, prevention of the action of the hormonal stimulator IGF-I on ovarian cells. It can be also suggested that the major GTPP effects may result from the presence of EGCG.

Montelukast Sodium Formulation Containing Green Tea Extract to Reduce the Oxidative Stress in Guinea Pig Model of Chronic Allergic Asthma.

The rationale of this study is that, treatment of asthmatic Guinea pig with combined administration of Montelukast sodium and Green Tea Extract (GTE) as a single capsule will mitigate the inflammatory injury in the airways and weaken the asthmatic response. Recent patents for the treatment of asthma researched a polyphenolic alternatives for antiasthmatic combination therapy, especially for those patients who remains unresponsive or poorly responsive for current asthma therapy (US7232585B2). Synergistic activity of green tea polyphenols and therapeutic, prophylatic agents are also reported in some recent patents (US20120172423A1, US20150320696A1). The present work is therefore aimed, to study the effect of Montelukast Sodium capsules coformulated with GTE on oxidative stress markers including Malondialdehyde (MDA), Glutathione (GSH) in different organs and Oxygen Radical Absorbance Capacity (ORAC) assay in plasma. Guinea pigs were placed in histamine chamber and exposed to an aerosol challenge of 0.2% w/v histamine dihydrochloride in distilled water using pressurized air driven nebulizer at a pressure of 0.05 MPa-0.106 MPa for one week. After that, they were divided in to four groups of three each; control, asthmatic control, asthmatic treated with marketed preparation and asthmatic received developed capsules. After oral administration of formulations for three days, pigs were scarificed and oxidative stress markers level including cytoarchitectural manifestation in tissues was studied. In comparison with the healthy control group, MDA level of the asthmatic animal liver and lung was found to be elevated as 0.059 ± 0.031(p < 0.002) and 0.802 ± 0.310 (p < 0.005) respectively, whereas GSH level was declined as 13.223 ± 1.485 (p < 0.0001) in liver and 3.037 ± 0.282 (p < 0.0004) in lung tissues. TAC of asthmatic animal plasma was low as 2.132 ± 0.986 mM Trolox Eq/L (p < 0.009). The level of these biomarkers reverts back towards normal after treatment with marketed and developed formulation, although treatment with developed formulation was more efficacious since it was coformulated with GTE, which acts as an adjuvant for the management of inflammatory disease like asthma. It is contemplated that, use of GTE as an adjuvant to anti leukotriene drug played a significant role in asthma management by reducing oxidant injury. Since, studies in animals do not directly translate to human biology, further multi-control studies with better sampled patient population and more number of patients are needed.

Role of green tea polyphenols in noise-induced hearing loss

Objective: To investigate the role and mechanism of action of green tea polyphenols in noise-induced hearing loss. Methods: Male specific pathogen-free guinea pigs were randomly divided into normal control group with 9 guinea pigs, noise exposure group with 36 guinea pigs, and green tea polyphenol intervention group with 36 guinea pigs. Auditory brainstem response (ABR) threshold shift was examined before noise exposure and at 1, 3, 7, and 14 days of noise exposure. The surface preparation of cochlear basilar membrane was used for hair cell count and the morphology of hair cells was also observed. Western blot was used to observe the expression of cysteinyl aspartate-specific protease-9 (caspase-9) and cysteinyl aspartate-specific protease-3 (caspase-3) in cochlear tissue. Results: Both the noise exposure group and the green tea polyphenol intervention group had an increase in ABR threshold after noise exposure, and the green tea polyphenol intervention group had a significantly lower ABR threshold shift than the noise exposure group at all time points (P<0.05). Both groups had enlargement, atrophy, or loss of hair cells after noise exposure, and at 7 and 14 days of noise exposure, the noise exposure group had a significantly higher rate of abnormal hair cells than the green tea polyphenol intervention group (P<0.05). Both groups had an increase in the expression of caspase-9 and caspase-3 after noise exposure, and the noise exposure group had a significantly greater increase than the green tea polyphenol intervention group (P<0.05). Conclusion: Green tea polyphenols can reduce noise-induced hearing loss and hair cell injury, possibly by regulating the expression of caspase-9 and caspase-3.

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.

Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes.

Osteoarthritis (OA) is a most common form of arthritis worldwide leading to significant disability. MicroRNAs (miRNAs) are non‐coding RNAs involved in various aspects of cartilage development, homoeostasis and pathology. Several miRNAs have been identified which have shown to regulate expression of target genes relevant to OA pathogenesis such as matrix metalloproteinase (MMP)‐13, cyclooxygenase (COX)‐2, etc. Epigallocatechin‐3‐O‐gallate (EGCG), the most abundant and active polyphenol in green tea, has been reported to have anti‐arthritic effects, however, the role of EGCG in the regulation of miRNAs has not been investigated in OA. Here, we showed that EGCG inhibits COX‐2 mRNA/protein expression or prostaglandin E2 (PGE 2) production via up‐regulating microRNA hsa‐miR‐199a‐3p expression in interleukin (IL)‐1β‐stimulated human OA chondrocytes. This negative co‐regulation of hsa‐miR‐199a‐3p and COX‐2 by EGCG was confirmed by transfection of OA chondrocytes with anti‐miR‐199a‐3p. Transfection of OA chondrocytes with anti‐miR‐199a‐3p significantly enhanced COX‐2 expression and PGE 2 production (P < 0.001), while EGCG treatment significantly inhibited anti‐miR‐199a‐3p transfection‐induced COX‐2 expression or PGE 2 production in a dose‐dependent manner. These results were further re‐validated by co‐treatment of these transfection OA chondrocytes with IL‐1β and EGCG. EGCG treatment consistently up‐regulated the IL‐1β‐decreased hsa‐miR‐199a‐3p expression (P < 0.05) and significantly inhibited the IL‐1β‐induced COX‐2 expression/PGE 2 production (P < 0.05) in OA chondrocytes transfected with anti‐hsa‐miR‐199a‐3p. Taken together, these results clearly indicate that EGCG inhibits COX‐2 expression/PGE 2 production via up‐regulation of hsa‐miR‐199a‐3p expression. These novel pharmacological actions of EGCG on IL‐1β‐stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG‐derived compounds inhibit cartilage breakdown or pain by up‐regulating the expression of microRNAs in human chondrocytes.

Inhibition of quorum sensing, biofilm, and spoilage potential in Shewanella baltica by green tea polyphenols.

We investigated the quorum sensing (QS) system of Shewanella baltica and the anti-QS related activities of green tea polyphenols (TP) against spoilage bacteria in refrigerated large yellow croaker. Autoinducer-2 (AI-2) and the diketopiperazines (DKPs) cyclo-(L-Pro-L-Leu) and cyclo-(L-Pro-L-Phe) were detected in the culture extract of S. baltica XH2, however, no N-acylhomoserine lactones (AHLs) activity was observed. Green TP at sub-inhibitory concentrations interfered with AI-2 and DKPs activities of S. baltica without inhibiting cell growth and promoted degradation of AI-2. The green TP treatment inhibited biofilm development, exopolysaccharide production and swimming motility of S. baltica in a concentration- dependent manner. In addition, green TP decreased extracellular protease activities and trimethylamine production in S. baltica. A transcriptional analysis showed that green TP repressed the luxS and torA genes in S. baltica, which agreed with the observed reductions in QS activity and the spoilage phenotype. Epigallocatechin gallate (EGCG)-enriched in green TP significantly inhibited AI-2 activity of S. baltica. These findings strongly suggest that green TP could be developed as a new QS inhibitor for seafood preservation to enhance shelf life.

Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1.

(-)-Epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea, has been demonstrated to have anticancer effects in a wide variety of human cancer. MicroRNAs (miRNAs) are a class of short noncoding RNAs and play important role in gene regulation and are critically involved in the pathogenesis and progression of human cancer. This study aims to investigate the effects of EGCG on osteosarcoma (OS) cells and elucidate the underlying mechanism. Cellular function assays revealed that EGCG inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis of OS cells in vitro, and also inhibited the growth of transplanted tumors in vivo. By miRNA microarray and RT-qPCR analysis, miR-1 was found to be significantly upregulated in MG-63 and U-2OS treated by EGCG in dose- and time-dependent manners, and miR-1 downregulation by inhibitor mimics attenuated EGCG-induced inhibition on cell growth of OS cells. We also confirmed that miR-1 was also frequently decreased in clinical OS tumor tissues. Moreover, both EGCG and miR-1 mimic inhibited c-MET expression, and combination treatment with EGCG and c-MET inhibitor (crizotinib) had enhanced inhibitory effects on the growth of MG-63 and U-2OS cells. Taken together, these results suggest that EGCG has an anticancer effect on OS cells, at least partially, through regulating miR-1/c-MET interaction.

Evaluation of the in vitro α-glucosidase inhibitory activity of green tea polyphenols and different tea types.

The objective of this study was to determine whether green tea, black tea and oolong tea have inhibitory potential against α-glucosidase which may be used to control postprandial hyperglycemia in type 2 diabetes mellitus. Green tea polyphenols (TPs) strongly inhibited α-glucosidase activity by non-competitive inhibition with an IC50 value of 2.33 µg mL(-1) and the inhibitory effect was dependent on TP concentration and incubation order. Green tea, black tea and oolong tea also had dose-dependent inhibitory potential with IC50 values of 2.82, 2.25 and 1.38 µg mL(-1) (µg polyphenol mL(-1)), respectively. The study also showed that the content of unprecipitated TPs changed during enzymatic hydrolysis, leading to the change of the antioxidant activity. The change of the antioxidant activity of tea extracts revealed a similar trend to that of green TPs during enzymatic hydrolysis. Green TPs, green tea, black tea and oolong tea are excellent α-glucosidase inhibitors and their inhibitory potency is mainly attributed to TPs. These findings suggest that green tea, black tea and oolong tea can potentially be used to control postprandial hyperglycemia.

In vitro and in vivo antioxidant and antimutagenic activities of polyphenols extracted from hops (Humulus lupulus L.)

Hops (Humulus lupulus L.) contain 40-140 mg g(-1) polyphenols. The objective of this study was to determine the phenolic composition of a high-purity (total phenolic content = 887 mg g(-1) ) hop polyphenol extract (HPE) and evaluate its antioxidant activities in vivo and in vitro and its antimutagenic activity. The antioxidant activity of HPE was compared with the activity of green tea polyphenols. The phenolic compositions of HPE were more than 55% proanthocyanidins and more than 28% flavonoid glycosides. In vitro, HPE effectively scavenged α,α-diphenyl-β-picrylhydrazyl, hydroxyl and superoxide anion radicals, and inhibited DNA oxidative damage. In vivo, oral HPE at a polyphenol dose of 200-800 mg kg(-1) body weight significantly prevented a bromobenzene-induced decrease in liver superoxide dismutase and glutathione peroxidase activity, and decreased levels of liver thiobarbituric acid reactive substances in bromobenzene-treated mice. An oral dose of 20-80 mg kg(-1) body weight HPE significantly reduced the frequency of bone marrow micronuclei induced by cyclophosphamide. The antioxidant activities of hop polyphenols in vitro and in vivo were higher than green tea polyphenols at the same concentration. Hop polyphenols had the same or higher antioxidant activity than tea polyphenols. Hop polyphenols might be useful as natural antioxidants and antimutagens.

Epimerization of Green Tea Catechins during Brewing Does Not Affect the Ability to Poison Human Type II Topoisomerases

(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea (Camellia sinensis) leaves, and many of its cellular effects are consistent with its actions as a topoisomerase II poison. In contrast to genistein and several related bioflavonoids that act as interfacial poisons, EGCG was the first bioflavonoid shown to act as a covalent topoisomerase II poison. Although studies routinely examine the effects of dietary phytochemicals on enzyme and cellular systems, they often fail to consider that many compounds are altered during cooking or cellular metabolism. To this point, the majority of EGCG and related catechins in green tea leaves are epimerized during the brewing process. Epimerization inverts the stereochemistry of the bond that bridges the B- and C-rings and converts EGCG to (-)-gallocatechin gallate (GCG). Consequently, a significant proportion of EGCG that is ingested during the consumption of green tea is actually GCG. Therefore, the effects of GCG and related epimerized green tea catechins on human topoisomerase IIα and IIβ were characterized. GCG increased levels of DNA cleavage mediated by both enzyme isoforms with an activity that was similar to that of EGCG. GCG acted primarily by inhibiting the ability of topoisomerase IIα and IIβ to ligate cleaved DNA. Several lines of evidence indicate that GCG functions as a covalent topoisomerase II poison that adducts the enzyme. Finally, epimerization did not affect the reactivity of the chemical substituents (the three hydroxyl groups on the B-ring) that were required for enzyme poisoning. Thus, the activity of covalent topoisomerase II poisons appears to be less sensitive to stereochemical changes than interfacial poisons.

Effects of a foot bath containing green tea polyphenols on interdigital tinea pedis

BackgroundIt has been shown that green tea polyphenols (GTP) can directly kill Trichophyton in vitro; however, there are no published clinical studies that show anti-fungal activity of GTP. ObjectivesTo identify the effects of GTP on interdigital tinea pedis in elderly patients. MethodNinety-four patients with interdigital tinea pedis were enrolled and were either given a lukewarm water foot bath containing GTP or placebo treatment. Effects of GTP were assessed based on changes in the size of the affected area, the rate of recurrence, microscopy findings, and overall assessment of skin changes. ResultsAfter 12 weeks of treatment with either GTP or placebo, a significant reduction in the size of the affected area was observed (p<0.001). There were no significant differences between the GTP or placebo groups in the size of the affected area (p=0.638), the recurrence rate (p=0.172), or the microscopy findings (p=1.000). However, the overall assessment demonstrated significant improvements (p=0.010) in the GTP group. ConclusionsThese results show that GTP was effective in improving the symptoms of tinea pedis in comparison to only lukewarm water. Our results suggest that GTP could have anti-fungal activity.