• Biomolecules & Therapeutics
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• 제21권1호
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• pp.54-59
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• 2013

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane $A_2$ ($TXA_2$) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration ($50{\mu}M$) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/$TXA_2$ signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

• 대한두경부종양학회지
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• 제27권1호
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• pp.3-11
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• 2011

Hepatocyte growth factor(HGF) and c-Met play an important role in the control of tumor growth and invasion, and they are known to be good prognostic indicators of patient outcome. Epigallocatechin-3-gallate (EGCG) has been shown to have chemopreventive and therapeutic properties by modulating multiple signal pathways regarding the control of proliferation and invasion of cells. In this study, we evaluated the role of c-Met in EGCG-induced inhibition of invasion and apoptosis in an oral cancer cell line. In KB cells where c-Met was knocked down with siRNA, we performed invasion assay and FACS with Annexin V-FITC/PT staining. In addition, we checked the change of mitochondrial membrane potential(MMP) and the generation of reactive oxygen species(ROS). EGCG-induced inhibition of invasiveness was significantly decreased after the knock-down of c-Met. EGCG-induced apoptosis, MMP change and ROS generation was also reduced in c-Met knock-ed-down KB cells. These results suggest that c-Met is involved in EGCG-induced apoptosis and inhibition of invasiveness of oral cancer cell line.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.259-266
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• 2011

The aim of this study was to evaluate the preventive role of epigallocatechin-3 gallate (EGCG, a derivative of green tea) in ischemia/reperfusion (I/R) injury of isolated rat hearts. It has been suggested that EGCG has beneficial health effects, including prevention of cancer and heart disease, and it is also a potent antioxidant. Rat hearts were subjected to 20 min of normoxia, 20 min of zero-flow ischemia and then 50 min of reperfusion. EGCG was perfused 10 min before ischemia and during the whole reperfusion period. EGCG significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/-dP/dtmax). EGCG also significantly increased the coronary flow (CF) at baseline before ischemia and at the onset of the reperfusion period. Moreover, EGCG decreased left ventricular end diastolic pressure (LVEDP). This study showed that lipid peroxydation was inhibited and Mn-SOD and catalase expressions were increased in the presence of EGCG. In addition, EGCG increased levels of Bcl-2, Mn-superoxide dismutase (SOD), and catalase expression and decreased levels of Bax and increased the ratio of Bcl-2/Bax in isolated rat hearts. Cleaved caspase-3 was decreased after EGCG treatment. EGCG markedly decreased the infarct size while attenuating the increase in lactate dehydrogenase (LDH) levels in the effluent. In summary, we suggest that EGCG has a protective effect on I/R-associated hemodynamic alteration and injury by acting as an antioxidant and anti-apoptotic agent in one.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.259-265
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• 2013

The anti-apoptotic effect of (-)-epigallocatechin-3-gallate (EGCG) during unilateral testicular torsion and detorsion (TT/D) was established in our previous study. In mice, the smallest inhibitor of apoptosis, survivin, is alternatively spliced into three variants, each suggested to have a unique function. Here, we assessed how EGCG exerts its protective effect through the expression of the different survivin splice variants and determined its effect on the morphology of the seminiferous tubules during TT/D. Three mouse groups were used: sham, TT/D+vehicle and TT/D treated with EGCG. The expression of the survivin variants (140 and 40) and other apoptosis genes (p53, Bax and Bcl-2) was measured with semi-quantitative RT-PCR. Histological analysis was performed to assess DNA fragmentation, damage to spermatogenesis and morphometric changes in the seminiferous tubules. In the TT/D+vehicle group, survivin 140 expression was markedly decreased, whereas survivin 40 expression was not significantly different. In parallel, there was an increase in the mRNA level of p53 and the Bax to Bcl-2 ratio in support of apoptosis induction. Histological analyses revealed increased DNA fragmentation and increased damage to spermatogenesis associated with decreased seminiferous tubular diameter and decreased germinal epithelial cell thickness in the TT/D+vehicle group. These changes were reversed to almost sham levels upon EGCG treatment. Our data indicate that EGCG protects the testis from TT/D-induced damage by protecting the morphology of the seminiferous tubules and modulating survivin 140 expression.

• 대한치과의사협회지
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• 제54권4호
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• pp.284-295
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• 2016

The aim of this study was to evaluate the effect of Epigallocatechin-3-Gallate (EGCG) on the alveolar bone metabolism in a collagen-induced arthritis (CIA) model in mice to enhance the understanding of rheumatoid arthritis (RA)-associated alveolar bone loss. Following the induction of CIA in animals (mice, n=16), mandibles were retrieved for micro-computed tomography (micro-CT) and isolation of alveolar bone cells (ABCs). In vitro osteogenic potentials of ABCs were evaluated and the mRNA expression of downstream effector genes was assessed. CIA was successfully induced in all animals, and micro-CT data showed that alveolar bone loss was significantly increased in the CIA group while the treatment of EGCG prevented the alveolar bone resorption. Osteogenesis by ABCs was significantly increased in the CIA+EGCG group in vitro. The analysis of mRNA expressions showed that osteoclastogenesis-associated genes were increased in CIA group while bone protecting genes were upregulated in EGCG treated group. The results demonstrate that EGCG downregulated the alveolar bone resorption in a CIA model in mice, and upregulation of bone protecting genes appear to be involved. Further studies are warranted.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.41-51
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• 2016

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activating TLR4-NF-${\kappa}B$ signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-${\kappa}B$ pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPS-induced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.163-169
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• 2007

The neurotoxicity of amyloid $\beta(A\beta)$ is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While(-)-epigallocatechin-3-gallate(EGCG) suppresses $A\beta$-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival system such as protein kinase C(PKC), extracellular-signal-related kinase(ERK), c-Jun N-terminal kinase(JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One ${\mu}M\;A{\beta}_{1-42}$ decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG($1{\mu}M$) significantly attenuated $A{\beta}_{1-42}$-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by $A{\beta}_{1-42}$ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the $A{\beta}_{1-42}$-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against $A{\beta}_{1-42}$-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.

• Journal of Chest Surgery
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• 제40권4호
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• pp.256-263
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• 2007

배경: 혈관내막과다증식은 혈관평활근세포가 내막에서 과다증식하여 나타나며, epigallocatechin-3-gallate(EGCG)는 혈관평활근세포의 증식을 억제하는 효과가 있는 것으로 알려져 있다. 따라서 EGCG는 혈관내막과다증식을 억제할 수 있을 것으로 생각된다. 대상 및 방법: 다른 농도의 EGCG를 포함한 배양 배지에서 인간제대정 맥내피세포(HUVEC)와 쥐대동맥평활근세포(RASMC)를 배양하고, 세포증식과 이동속도를 측정하였다. 20마리의 개의 양측 경동맥에 자가경정맥을 이식하였으며, 실험군(n=10)에 대해서는 정맥도관을 이식 전 30분간 EGCG용액에 보관하였으며, 이식 후 300mM의 EGCG를 혈관주위에 도포하였다. 6주 후에 경정맥이식편의 내막과 중간막의 두께를 측정하였다. 결과: 내피세포와 혈관평활근세포의 증식은 EGCG에 의해 억제되었다. 혈관평활근세포의 이동성은 EGCG에 의해 억제되었으나, 내피세포의 이동성은 영향을 받지 않았다. 동물실험 결과 대조군에 비해 EGCG군에서 내막의 두께가 얇았으며(p<0.05), 중간막의 두께는 두 군간에 차이가 얼었고, 내막/중간막의 두께비는 EGCG군에서 낮게 관찰되었다(p<0.05). 결론: EGCG는 혈관수술 후 혈관내막과다증식을 억제하는 효과가 있으며, 이는 혈관평활근세포의 증식 및 이동을 억제하여 효과를 나타낸다고 생각된다. 따라서 EGCG는 혈관내막과다증식을 예방하는 치료에 효과적으로 사용될 수 있을 것으로 생각된다.

• 한국식품과학회지
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• 제43권4호
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• pp.483-489
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• 2011

본 연구에서는 다양한 생리활성이 보고된 폴리페놀 화합물인 EGCG의 화학안정성, H2O2 생성능 및 세포독성에 대하여 다양한 항산화제와의 조합에 의한 변화를 분석하였다. EGCG는 생리적 조건에서 갈색화합물로 산화되면서 불안정화되는데, catalase를 제외한 각종 항산화제제 SOD, ascorbic acid, NAC 및 GSH는 EGCG 갈색산화물의 생성을 유의적으로 저해하였다. EGCG에 의해 생성되는 $H_2O_2$는 catalase에 의해 거의 완벽하게 제거되었으며, SOD와 NAC에 의해서도 유의적으로 감소하였다. 하지만 GSH 및 고농도의 ascorbic acid의 존재 시 오히려 $H_2O_2$ 수준이 증가하는 현상을 나타내었다. EGCG의 HeLa 및 HT-29 세포에 대한 독성은 catalase, SOD 및 NAC 등과 같은 항산화제 존재 하에 유의적으로 감소하였고 NAC에 의한 EGCG 세포독성의 감소는 첨가된 NAC의 농도 증가에 따라 더욱 두드러졌다. 그러나 GSH 존재하에 EGCG의 독성은 GSH와 EGCG농도에 따라 다른 조절 양상을 나타내었으며, ascorbic acid에 의해서 EGCG의 세포독성이 약간 증가하는 현상을 나타내었다. 본 결과는 EGCG와 함께 처리된 다양한 항산화제들이 ROS의 소거 뿐만 아니라 EGCG 화학안정성 등 다른 요인에 영향을 미칠 수 있으며, 항산화제의 존재 하에 변형된 EGCG활성에 대해 ROS관련 기작 외에 다양한 요인들에 대한 고려가 함께 이루어져야 함을 시사한다.