• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.203-210
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• 2015

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

• Natural Product Sciences
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• v.22 no.2
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• pp.87-92
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• 2016

Endothelial dysfunction in atherosclerosis is associated with increasing oxidative stress that could be reversed by antioxidant. Therefore epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and catechin (C) of tea flavonoids were investigated for their roles in regenerating endothelial cell. Peripheral blood mononuclear cells (PB-MNCs) were isolated, plated and cultured in medium with/without treatment of EGCG, ECG, EGC and C. Results showed that among all EGCG, ECG, EGC and C concentrations tested, $12.5{\mu}mol/L$ was not cytotoxic for peripheral blood-derived endothelial progenitor cells (PB-EPCs). Treatment of EGCG, ECG, EGC or C increased the percentages of CD34, CD133, VEGFR-2 expressions and suppressed hydrogen peroxide-induced percentages of reactive oxygen species (ROS) level in PB-EPCs. Taken together, our current results showed that EGCG, ECG, EGC or C of tea flavonoids could induce differentiation of PB-MNCs into PB-EPCs as well as protect PB-EPCs from oxidative damage by suppresing the intracellular ROS levels.

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.238-244
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• 2003

Nicotine is one of the major hazardous components in cigarettc smoke. Nicotine deals a harmful effect to smokers and passive smokers due to its rapid conversion to various carcinogenic metabolites. Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is believed to cause lung cancers among the nicotine-derived carcinogens. Recent studies report that NNK synthesis can be inhibited by the metabolism pathway to produce a stable metabolite cotinine from nicotine. Tea polyphenols have been known to contain factors to prevent cancers and to retard progression of cancers. This study aims to correlate tea polyphenol's potential for cancer prevention with an accelerated formation of cotinine. The conversion from nicotine to cotinine in the presence of tea extracts or three polyphenols (Catechin, epicatechin gallate, epigallocatechin gallate) was measured in established cell lines and in Xenopus oocytes. Among three lines of cell used, PLC/PRF5 and HEK293 cells showed a fast turnover from nicotine to cotinine while HepG2 cell line showed a marginal difference between groups treated and non-treated with tea polyphenols. When Xenopus oocytes were microinjected with nicotine, tea polyphenols appear to accelerate the conversion of nicotine to cotinine. Among the polyphenols tested in this study, (＋)－catechin showed the best efficiency overall in accelerating conversion from nicotine to cotinine both in the cell lines and in the oocytes. In summary, the present study indicated that tea polyphenols have a positive effect on conversion of nicotine to cotinine.

• Integrative Medicine Research
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• v.3 no.1
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• pp.25-33
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• 2014

Background: Green tea contains numerous polyphenols, which have health-promoting effects. The purpose of this study was to evaluate the effect of tannase-converted green tea extract (TGE) formulation on the physical stability and activities of skin-related enzymes. Methods: Physical stability was evaluated by measuring the pH, precipitation, and colors at $25{\pm}2^{\circ}C$ /ambient humidity and at $40{\pm}2^{\circ}C$ \70%${\pm}$5% relative humidity for 4 months. Activities of collagenase, elastase, and tyrosinase as skin-related enzymes were assessed on TGE formulation. Results: The concentrations of epigallocatechin-3-gallate and epicatechin-3-gallate in green tea extract were greatly decreased to the extent of negligible level when treated with tannase. The formulation containing 5% tannase-converted green tea extract showed relatively stable pH, precipitation, and color features for 16 weeks. When TGE was added to the formulation, there was a significant increase in the inhibition of elastase and tyrosinase activities (p<0.05) compared with the formulation containing 5% normal green tea extract. Conclusion: The TGE could be used in cosmetics as skin antiwrinkling or depigmenting agent.

• Journal of Periodontal and Implant Science
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• v.49 no.2
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• pp.114-126
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• 2019

Purpose: The aim of this study was to evaluate the enhancement of osteogenic potential of biphasic calcium phosphate (BCP) bone substitute coated with Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) and epigallocatechin-3-gallate (EGCG). Methods: The cell viability, differentiation, and mineralization of osteoblasts was tested with ErhBMP-2-/EGCG solution. Coated BCP surfaces were also investigated. Standardized, 6-mm diameter defects were created bilaterally on the maxillary sinus of 10 male New Zealand white rabbits. After removal of the bony windows and elevation of sinus membranes, ErhBMP-2-/EGCG-coated BCP was applied on one defect in the test group. BCP was applied on the other defect to form the control group. The animals were sacrificed at 4 or 8 weeks after surgery. Histologic and histometric analyses of the augmented graft and surrounding tissue were performed. Results: The 4-week and 8-week test groups showed more new bone (%) than the corresponding control groups (P<0.05). The 8-week test group showed more new bone (%) than the 4-week test group (P<0.05). Conclusions: ErhBMP-2-/EGCG-coated BCP was effective as a bone graft material, showing enhanced osteogenic potential and minimal side effects in a rabbit sinus augmentation model.

• Journal of the Korean Wood Science and Technology
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• v.31 no.6
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• pp.67-72
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• 2003

The leaves of D. racemosum showed strong DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and the order of the radical scavenging activity against DPPH radical is ethyl acetate (EtOAc) fraction>crude extracts>residue fraction>hexane fraction>ether fraction, under the experimental conditions. Since EtOAc fraction has highest antioxidative activity among these fractions, the isolation was performed from the EtOAc fraction of the leaves of D. racemosum and four phenolic compounds were isolated and identified as follows: methyl gallate, kaempferol, quercetin and quercitrin. The free radical scavenging activities of these compounds were 79.9%, 93.1%, 93.6% and 66.7% at 10 ㎍/ml, respectively. The IC₅₀ of compound 1, compound 2, compound 3 and compound 4 were 6.1, 4.1, 3.6 and 6.5 ㎍/ml, respectively. These compounds have higher antioxidative activity compared with reference compounds, ascorbic acid (IC₅₀ = 9.6 ㎍/ml).

• Journal of the Korean Society of Food Culture
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• v.22 no.4
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• pp.449-453
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• 2007

Using green tea(GT), oolong tea(OT), black tea(BT) and green tea bag(GTB) out of tea products in market, this study quantified polyphenol and catechins as anti-oxidant substances and analyzed their respective anti-oxidant capacities. As a result, more epigallocathechin(EGC) was found in GT and GTB as well as caffein(CAF) in GT and BT. GT contained more epigallocathechin gallate(EGCG) than other tea types. Both FRAP and ORAC, as two methods of analyzing anti-oxidant capacities, showed that GTB had highest anti-oxidant capacities, while OT had lowest of all. By brand, it was found that all the 3 brands of GT had similarly high anti-oxidant capacities, but there were differences in the anti-oxidant activities of GTB and BT depending on brand. Out of catechin components, it was found that epicatechin(EC), epicathechin gallate(ECG) and EGCG were major components affecting anti-oxidant capacities.

• Journal of Life Science
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• v.25 no.9
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• pp.961-969
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• 2015

Epigallocatechin gallate (EGCG), the main catechin in green tea, has been shown to have some beneficial effects against various human diseases, including diabetes, neurodegenerative disorders, cancer, cardiovascular disease and obesity. To investigate the mechanism of the suppressive effects of EGCG on inflammatory response in macrophages, alterations on the levels of nitric oxide (NO) regulatory factors and inflammatory cytokines were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells. No significant toxicity was detected in RAW264.7 cells treated with 100–400 μM EGCG. Moreover, the optimal concentration of LPS was determined to be 1 μg/ml based on the results of cell viability assay, NO assay and IL-6 enzyme-linked immunsorbent assay (ELISA). Furthermore, NO levels decreased significantly by 68.2% in the 400 μM EGCG/LPS treated group, while the level of inducible nitric oxide synthase (iNOS) expression decreased by 12-17% in the 200 and 400 μM EGCG/LPS treated group. A significant decrease in transcription of pro-inflammatory cytokines (TNF- α and IL-1β) and anti-inflammatory cytokine (IL-10) was also detected in the EGCG/LPS treated group. However, IL-6 transcript and protein was maintained at a constant level when in the LPS treated group relative to the EGCG/LPS treated group. Overall, these results suggest that the differential regulation of inflammatory cytokines is an important factor influencing the suppressive effects of EGCG against LPS-activated inflammatory response in RAW264.7 cells.

• Korean Journal of Food Science and Technology
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• v.43 no.6
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• pp.766-772
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• 2011

This study was conducted to evaluate the daily intakes of propyl gallate, EDTA (ethylenediamine tetra acetate), and erythorbic acid for average consumers by age group and the intake of high consumers ($95^{th}$ percentile) in Korea. The average intake of EDTA was $1.14{\mu}g/kg{\cdot}bw/day$, and 0.0% of the ADI (acceptable daily intake) established by JECFA (Joint FAO/WHO Expert Committee on Food Additives). The $95^{th}$ percentile intake of EDTA was $141.24{\mu}g/kg{\cdot}bw/day$ (5.6% of ADI). The average intake of erythorbic acid was $16.93{\mu}g/kg{\cdot}bw/day$, and the 3-6 year-old group had the highest consumption ($58.43{\mu}g/kg{\cdot}bw/day$), which was <1.0% of the ADI established by the EU (European Union). The $95^{th}$ percentile intake of erythorbic acid was $1,320.31{\mu}g/kg{\cdot}bw/day$ and 22.0% of the ADI. In conclusion, daily intakes of propyl gallate, EDTA, and erythorbic acid in Korea were at safe levels in all age groups and also in high consumers.

• Archives of Pharmacal Research
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• v.23 no.6
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• pp.605-612
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• 2000

Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase IIgene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 $\mu\textrm{m}$with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 $\mu\textrm{m}$ to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP.