• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.6
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• pp.2660-2667
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• 2011

TREK-1 channel is a member of the two-pore domain potassium (K2P) channel family that is regulated by intracellular pH, membrane stretch, polyunsaturated fatty acids, temperature, and some neuroprotectant agents. TREK-1 channel can influence neuronal excitability by regulating leakage of potassium ions and resting membrane potential. TREK-1 channel has been shown to be overexpressed in prostate cancer cells. Although the importance of these properties, relatively little is known about flavonoid effects in the regulations of TREK-1 channel. The purpose of the study was to screening of flavonoids as the TREK-1 channel modulator using one of electrophysiological techniques such as excised inside-out patch configuration. We demonstrated blocking effect on TREK-1 channel by flavonoids such as epigallocatechin-3-gallate (EGCG), curcumin and quercetin in CHO cells transiently expressing TREK-1 channel. The inhibition of TREK-1 channel by quercetin and curcumin was reversible, whereas EGCG was little reversible. Quercetin, EGCG and curcumin decreased the relative channel activity to 73%, 91% and 94%, respectively. The half-inhibitory concentration (IC50) of curcumin, quercetin and EGCG was $1.04{\pm}0.19\;{\mu}M$, $1.13{\pm}0.26\;{\mu}M$ and $13.5{\pm}2.20\;{\mu}M$ in CHO cells expressing TREK-1 channel, respectively. These results indicate that flavonoids might regulate TREK-1 and this regulation might be one of the pharmacological actions of flavonoid in nervous systems and cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.47-51
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• 2004

Green tea, which is high in polyphenols, is thought to have hypocholesterolemic effects. The present study was performed to further elucidate the hypocholesterolemic actions of green tea, specially the catechin and (-)-epigallocatechin gallate (EGCG) for their effects on the diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats were fed with green tea-free diet (control), diets containing 4% green tea powder (GTP), 1.0% green tea catechin (catechin) or 0.5% epigallocatechin gallate (EGCG) for 7 wks. All diets that were provided green tea contained approximately 0.5% EGCG Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. There were no differences in food intake among groups. The green tea treatments showed significant improvement in the serum levels of total cholesterol, LDL-cholesterol, triacylglycerides and atherogenic index in the following order; EGCG>Catechin>GTP (p<0.05). The serum HDL-cholesterol level was highest in the EGCG-treated group. The catechin or EGCG diet up-regulated by 5 times the enzyme activity of hepatic cholesterol 7$\alpha$ -hydroxylase (CYP7Al) compared to control diet (p<0.05). Hepatic CYP7Al mRNA level paralleled tile increases in the CYP7Al activity. These results suggest that the EGCG in the green tea may account for the hypocholesterolemic effect by the induction of CYP7Al gene expression.

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.298-303
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• 2009

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.9
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• pp.1420-1430
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• 2018

Objective: Epigallocatechin-3-gallate (EGCG) is a major ingredient of catechin polyphenols and is considered one of the most promising bioactive compounds in green tea because of its strong antioxidant properties. However, the protective role of EGCG in bovine oocyte in vitro maturation (IVM) has not been investigated. Therefore, we aimed to study the effects of EGCG on IVM of bovine oocytes. Methods: Bovine oocytes were treated with different concentrations of EGCG (0, 25, 50, 100, and $200{\mu}M$), and the nuclear and cytoplasmic maturation, cumulus cell expansion, intracellular reactive oxygen species (ROS) levels, total antioxidant capacity, the early apoptosis and the developmental competence of in vitro fertilized embryos were measured. The mRNA abundances of antioxidant genes (nuclear factor erythriod-2 related factor 2 [NRF2], superoxide dismutase 1 [SOD1], catalase [CAT], and glutathione peroxidase 4 [GPX4]) in matured bovine oocytes were also quantified. Results: Nuclear maturation which is characterized by first polar body extrusion, and cytoplasmic maturation characterized by peripheral and cortical distribution of cortical granules and homogeneous mitochondrial distribution were significantly improved in the $50{\mu}M$ EGCG-treated group compared with the control group. Adding $50{\mu}M$ EGCG to the maturation medium significantly increased the cumulus cell expansion index and upregulated the mRNA levels of cumulus cell expansion-related genes (hyaluronan synthase 2, tumor necrosis factor alpha induced protein 6, pentraxin 3, and prostaglandin 2). Both the intracellular ROS level and the early apoptotic rate of matured oocytes were significantly decreased in the $50{\mu}M$ EGCG group, and the total antioxidant ability was markedly enhanced. Additionally, both the cleavage and blastocyst rates were significantly higher in the $50{\mu}M$ EGCG-treated oocytes after in vitro fertilization than in the control oocytes. The mRNA abundance of NRF2, SOD1, CAT, and GPX4 were significantly increased in the $50{\mu}M$ EGCG-treated oocytes. Conclusion: In conclusion, $50{\mu}M$ EGCG can improve the bovine oocyte maturation, and the protective role of EGCG may be correlated with its antioxidative property.

• Korean Journal of Microbiology
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• v.52 no.3
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• pp.260-268
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• 2016

The aim of this work was to investigate the cellular responses and proteomic analysis of Bacillus cereus MH-2 exposed to EGCG. Strain MH-2 was isolated from commercial Ssamjang and has the hemolytic activity. Survival of the MH-2 strain with time in the presence of different concentrations of EGCG under sublethal conditions was monitored. The amount of alginate from MH-2 strain decreased depending on the increasing concentrations of EGCG and increased depending on the exposure time at any particular EGCG concentration. Analysis of SDS-PAGE and Western blot using anti-DnaK and anti-GroEL revealed that two stress shock proteins, 70 kDa DnaK and 60 kDa GroEL were found to decrease in proportion to the EGCG concentration in exponentially growing cultures. Scanning electron microscopic analysis demonstrated the presence of protrusions and fused rod forms on the cells treated with EGCG. 2-DE of soluble protein fractions from MH-2 cultures showed 20 protein spots changed by EGCG exposure. These proteins involved in enterotoxins (hemolysin BL lytic component L1 and hemolysin BL-binding protein), chaperons (DnaK and GroEL), cell defense (peptidase M4 family proteins), and various biosynthesis and energy metabolism were identified by peptide mass fingerprinting using MALDI-TOF. These results provide clues for understanding the mechanism of EGCG-induced stress and cytotoxicity on B. cereus MH-2.

• Tuberculosis and Respiratory Diseases
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• v.76 no.3
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• pp.114-119
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• 2014

Background: Epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, has anti-cancer activity in human and animal models. We investigated the schedule-dependent effect of EGCG and paclitaxel on growth of NCI-H460 non-small cell lung cancer cells. Methods: To investigate the combined effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated, and cell cycle analysis was performed. For the effect on cell apoptosis, western blot analysis was also performed. Results: CI analysis demonstrated that both concurrent and sequential E ${\rightarrow}$ P treatments had antagonistic effects (CIs >1.0), but sequential P ${\rightarrow}$ E had synergistic effects (CIs <1.0), on the growth inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel induced $G_2/M$ cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG and paclitaxel treatments did not have any additive or synergistic effects compared with the paclitaxel treatment alone. However, western blot analysis demonstrated that sequential P ${\rightarrow}$ E treatment decreased the expression of Bcl-2 and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while minimal effects were seen with concurrent or sequential E ${\rightarrow}$ P treatments. Conclusion: Concurrent or sequential E ${\rightarrow}$ P treatment had opposite effects to P ${\rightarrow}$ E treatment, where P ${\rightarrow}$ E treatment showed a synergistic effect on growth inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG and paclitaxel combination treatment seems to be schedule-dependent.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.420-426
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• 2007

In the present investigation, we studied the modulating effects of (-)-epigallocatechin-3-gallate(EGCG) on the differentiation of mouse C2C12 myoblasts. We found that the strong inhibitory effect of EGCG on DNA methyltransferase-mediated DNA methylation induced transdifferentiation of C2C12 myoblasts into smooth muscle cells demonstrated by both morphological changes and immunofluorescent staining. C2C12 myoblasts treated with EGCG for 4 days expressed smooth muscle ${\alpha}-actin$ protein. Real-time PCR data revealed that smooth muscle ${\alpha}-actin$ mRNA was induced by EGCG treated C2C12 myoblasts in a concentration-dependent manner. Smooth muscle ${\alpha}-actin$ mRNA concentration increased 330% and 490% after 2 and 3 days of 50 ${\mu}M$ of EGCG treatment. The expression of another smooth muscle marker, transgelin, mRNA was also increased up to 9-fold by 4 days of EGCG treatment compared with control in a concentration-dependent manner. These results suggested that C2C12 enables to transdifferentiate into smooth muscle when gene expression patterns are changed by the inhibition of DNA methylation induced by EGCG. In conclusion, transdifferentiation of C2C12 myoblasts into smooth muscle is resulted from the modulating effects of EGCG on DNA methylation which subsequently results in changing the expression pattern of several genes playing a critical role in the differentiation of C2C12 myoblasts.

• Journal of Life Science
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• v.32 no.11
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• pp.841-846
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• 2022

The purpose of this study was to evaluate the antioxidant properties of Rosa rugosa extract and to identify which of its components are responsible for these properties. Reactive oxygen species play an important role in diseases such as cancer, arteriosclerosis, and heart disease as a consequence of increased metabolic rates, gene mutations, and relative hypoxia. Therefore, the antioxidant effect of R. rugosa extract was confirmed by HPLC, HPLC-MS/MS, the total polyphenol content, the total flavonoid content, and the radical scavenging activity. HPLC and HPLC-MS/MS analyses were conducted to identify and quantify the main components of the R. rugosa extract. Gallic acid and epigallocatechin gallate were identified as the main components, with 17.4 and 4.35 mg/g dry matter (DM), respectively. The antioxidant activity of R. rugosa extract was evaluated based on its total polyphenol content, total flavonoid content, and radical scavenging activity, which were 72.3 mg gallic acid equivalent/g DM, 11.2 mg quercetin equivalent/g DM, and 87.9%, respectively. The radical scavenging activities of the main components, gallic acid and epigallocatechin gallate, were 80.5% and 89.7%, respectively. Therefore, R. rugosa has a high polyphenol content and antioxidant activity, and it can be used as a natural antioxidant in food, cosmetics, and pharmaceuticals.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.74.1-74.16
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• 2022

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

• BMB Reports
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• v.42 no.1
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• pp.41-46
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• 2009

Post-transcriptional regulation of mRNA stability by Hu proteins is an important mechanism for tumorigenesis. We focused on the molecular interactions between the HuC protein and AU-rich elements (AREs) to find chemical inhibitors of RNA-protein interactions using RNA electrophoretic mobility shift assay with non-radioactive probes. Screening of 52 natural compounds identified 14 candidate compounds that displayed potent inhibitory activity. Six (quercetin, myricetin, (-)-epigallocatechin gallate, ellagic acid, (-)-epicatechin gallate, and rhamnetin) were categorized as phytochemicals, and their $IC_{50}$ values were low ($0.2-1.8\;{\mu}M$).