Inhibitory Effects of (-) Epigallocatechin Gallate and Quercetin on High Glucose-induced Endothelial Cytotoxicity

Yean-Jung Choi,Hyang-Mi Kwon,Jung-Suk Choi,Ji-Young Bae,Sang-Wook Kang,Sang-Soo Lee,Yong-Jin Lee,Young-Hee Kang 한국영양학회 2006 Nutritional Sciences Vol.9 No.1

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factors in the impaired wound healing seen with diabetes mellitus. It is also thought that oxidative stress plays a significant role in this endothelial cell dysfunction. The present study examined the differential effects of flavonoids on endothelial cell dysfunction under high glucose condition. Human endothelial cells exposed to 30 m㏖/ℓ glucose for 7 d were pre-treated with various flavonoids and pulse-treated with 0.2 m㏖/ℓ H₂O₂ for 30 min. High glucose markedly decreased cell viability with elevated oxidant generation and nuclear condensation, H₂O₂ insult exacerbated endothelial cytotoxicity due to chronic exposure to high glucose. (-)Epigallocatechin gallate and quercetin improved glucose-induced cell damage with the disappearance of apoptotic bodies, whereas apigenin intensified the glucose cytotoxicity. In addition, cell viability data revealed that these flavonoids of (-)epigallocatechin gallate and quercetin substantially attenuated both high glucose- and H₂O₂- induced dual endothelial damage. 'These results suggest that (- )epigallocatechin gallate and quercetin may be beneficial agents for improving endothelial cell dysfunction induced by high glucose and may prevent or reduce the development of diabetic vascular complications.

장중첩증으로 발현된 원발성 림프종 1예

정태연,손석만,이창화,이원재,백승덕,최우혁,정희철,정소연,김남일,서정일,양창헌,이창우,정기훈,김정란 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.2

위장관은 악성 림프종이 가장 흔히 침범하는 림프절 외 장기이지만, 원발성 소장 악성림프종이 비교적 드물게 발생한다. 장중첩증은 장 림프종의 드문 징후이며, 다양한 영상 검사에 의하여 진단된다. 저자들은 회장 장중첩증에 의해 우연히 발견된 림프종의 예를 보고하는 바이다. 조직학적 소견은 미만성 대 B 세포의 악성 림프종이였고, 중증도의 미만성 대비분열성세포이였다. 환자는 수술적인 절제술과 항암요법을 시행하였고 15개월간 재발이 없는 상태로 추적 관찰 중이다. Although the gastrointestinal tract is one of the most frequent sites of extranodal malignant lymphoma, the occurrence of primary small intestinal lymphoma is relatively uncommon. The intussusception is a rare presenting sign of intestinal lymphoma, and diagnosed by various imaging studies. We report on a case of the lymphoma on ileum manifested by ileo-ileal intussusception. Pathologic type was malignant lymphoma with diffuse large B cell (REAL classification), intermediate grade, diffuse large noncleaved cell (Working formulation). The patient received surgical resection and combined chemotherapy and doing well for 15 months.

Inhibitory Effects of (-) Epigallocatechin Gallate and Quercetin on High Glucose-induced Endothelial Cytotoxicity

Choi Yean Jung,Kwon Hyang Mi,Choi Jung Suk,Bae Ji Young,Kang Sang Wook,Lee Sang Soo,Lee Yong Jin,Kang Young Hee The Korean Nutrition Society 2006 Nutritional Sciences Vol.9 No.1

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factor.; in the impaired wound healing seen with diabetes mellitus. It is also thought that oxidative stress plays a significant role in this endothelial cell dysfunction. The present study examined the differential effects of flavonoids on endothelial cell dysfunction under high glucose conditions. Human endothelial cells exposed to 30 mmol/L glucose for 7 d were pre-treated with various flavonoids and pulse-treated with 0.2 mmol/L $H_2O_2$ for 30 min. High glucose markedly decreased cell viability with elevated oxidant generation and nuclear condensation. $H_2O_2$ insult exacerbated endothelial cytotoxicity due to chronic exposure to high glucose. (-)Epigallocatechin gallate and quercetin improved glucose-induced cell damage with the disappearnnce of apoptotic bodies, whereas apigenin intensified the glucose cytotoxicity. In addition, cell viability data revealed that these flavonoids of (-)epigallocatechin gallate and quercetin substantially attenuated both high glucose- and $H_2O_2$- induced dual endothelial damage. These results suggest that (-)epigallocatechin gallate and quercetin may be beneficial agents for improving endothelial cell dysfunction induced by high glucose and may prevent or reduce the development of diabetic vascular complications.

Dietary Flavonoids Differentially Reduce Oxidized LDL-Induced Apoptosis in Human Endothelial Cells: Role of MAPK- and JAK/STAT-Signaling

Choi, Jung-Suk,Choi, Yean-Jung,Shin, Sung-Yong,Li, Jing,Kang, Sang-Wook,Bae, Ji-Young,Kim, Dong Shoo,Ji, Geun-Eog,Kang, Jung-Sook,Kang, Young-Hee Oxford University Press 2008 The Journal of nutrition Vol.138 No.6

<P>Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized LDL promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. This study investigated multiple mitogen-activated protein kinase (MAPK)-responsive death/survival signaling pathways, through which flavonoids of (-)epigallocatechin gallate (EGCG) and hesperetin exerted antiapoptosis in endothelial cells exposed to oxidized LDL. EGCG and hesperetin substantially diminished the oxidized LDL-induced 2',7'-dichlorofluorecein staining, suggesting that these flavonoids inhibited intracellular accumulation of oxidized LDL-triggered reactive oxygen species and consequent apoptosis. The Western-blot data revealed that oxidized LDL upregulated c-Jun N-terminal kinase (JNK) phosphorylation, which was rapidly reversed by EGCG and hesperetin. They mitigated the consequent activation of the JNK downstream on p53 and c-Jun. Moreover, oxidized LDL increased luciferase activity of p53 in endothelial cells transfected with a p53 promoter construct, the increase of which was strikingly downregulated by EGCG and hesperetin. Surprisingly, hesperetin but not EGCG attenuated phosphorylation of p38MAPK and its downstream c-myc and signal transducers and activators of transcription (STAT)1 evoked by oxidized LDL. This study also attempted to explore a linkage of Janus kinase (JAK)2/STAT3 activation to MAPK signaling in oxidized LDL-induced endothelial apoptosis. Notably, we found that the JAK2 inhibitor substantially blocked the JNK activation. Our findings suggest that EGCG and hesperetin may act as antiatherogenic agents blocking oxidized LDL-induced endothelial apoptosis via differential cellular apoptotic machinery. These data provide evidence that the interplay between p38MAPK and JAK-STAT pathways is involved in dietary flavonoid protection against oxidized LDL through hampering MAPK-dependent pathways involving the activation of JAK2.</P>

(-)Epigallocatechin Gallate and Quercetin Enhance Survival Signaling in Response to Oxidant-Induced Human Endothelial Apoptosis

Choi, Yean-Jung,Jeong, Yu-Jin,Lee, Yong-Jin,Kwon, Hyang-Mi,Kang, Young-Hee Oxford University Press 2005 The Journal of nutrition Vol.135 No.4

종양괴사인자에 의하여 유도된 혈관내피세포의 Cell Adhesion Molecules 발현을 억제시키는 플라보노이드 선별

최정숙(Jung-Suk Choi),최연정(Yean-Jung Choi),박성희(Sung-Hee Park),이용진(Yong-Jin Lee),강영희(Young-Hee Kang) 한국식품영양과학회 2002 한국식품영양과학회지 Vol.31 No.6

염증성 cytokines의 분비 또는 혈관손상으로 인한 백혈구의 adhesion과 transmigration을 통하여 죽상경화과정이 시발되는데, 본 연구에서는 이러한 죽상경화의 초기과정에서 플라보노이드가 억제작용을 발휘하는 지를 규명하고자 하였다. 본 연구에서는 화학적인 구조가 서로 다른 플라보노이드를 사용하여 화학적인 구조와 항동맥경화작용과의 상관성을 확인하였다. TNF-α는 혈관내피세포를 활성화시켜 THP-1 단핵구의 adhesion을 유의적으로 증가시켰다. 여러 형태의 플라보노이드를 전처리하고 TNF-α를 가하여 혈관내피세포를 활성화 시켰을 때, flavonols인 quercetin과 flavones의 luteolin과 apigenin은 THP-1 단핵구의 adhesion 억제효과를 보여주었다. 그러나, catechins과 flavanones의 플라보노이드는 이러한 억제효과를 전혀 보여주지 못하였다. 이러한 adhesion 억제작용을 가지는 플라보노이드는 CAMs 단백질의 발현도 차단시킨다는 것을 확인할 수 있었다. Quercetin, luteolin과 apigenin은 TNF-α에 의하여 증가된 VCAM-1, ICAM-1 및 Eselectin의 단백질 발현을 일률적으로 감소 또는 차단시켰다. 그 대신, 단핵구의 adhesion을 차단시키지 못한 (-)epigallocatechin gallate와 (+)catechin은 TNF-α에 의한 이러한 CAMs의 발현을 전혀 억제시키지 못하였다. 또한 quercetin, luteolin과 apigenin의 CAMs 단백질 발현 억제작용은 유전자 전사단계에서 mRNA의 down-regulation으로 인하여 나타난다는 사실을 알 수 있었다. 결론적으로 quercetin, luteolin, apigenin과 같은 플라보노이드는 TNF-α와 같은 염증성 cytokines에 의한 단핵구의 adhesion을 혈관내피세포의 CAMs단백질 발현을 억제하므로서 차단시킨다는 것이 확인되었다. 여기서 모든 플라보노이드가 이러한 활성을 다 지니고 있지 않아서 화학적인 구조와 초기 항동맥경화작용에는 서로 연관성이 있다는 것이 제시되었다. 또한, 선별된 플라보노이드의 초기 항동맥경화작용은 활성산소를 소거하는 플라보노이드의 항산화능과는 무관한 것 같다고 할 수 있다. Adhesion of leukocytes to the activated vascular endothelium and their subsequent recruitment/migration into the artery wall are key features in the pathogenesis of atherosclerosis and inflammatory diseases. These features have been mediated by cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and in- tracellular cell adhesion molecule-1 (ICAM-1). This study examined whether flavonoids inhibit the pro-inflam- matory cytokine TNF-α-induced monocyte adhesion via a modulation of the protein expression of VCAM-1 and ICAM-1 of human umbilical vein endothelial cells (HUVECs). TNF-α markedly increased the adhesion of THP-1 monocytes to endothelial cells and induced the expression of VCAM-1, ICAM-1 and E-selectin proteins in HUVECs. Micromolar concentrations of the flavones luteolin and apigenin and the flavonol quercetin near- completely blocked the monocyte adhesion to the activated endothelial cells and the induction of these adhesion molecules. However, equimicromolar catechins of (-)epigallocatechin gallate and (+)catechin, the flavonol myr- icetin and the flavanones of naringin and hesperidin had no effect on TNF-α-activated monocyte adhesion. (-)Epigallocatechin gallate, (+) catechin, and naringin did not attenuate the TNF-α induction of these adhesion molecules. Furthermore, culture with luteolin and apigenin strongly blocked the expression of TNF-α-induced VCAM-1 mRNA and modestly attenuated ICAM-1 mRNA. Quercetin modestly decreased the TNF-α-activated VCAM-1 and ICAM-1 mRNAs. These results demonstrate that flavonoids classified as flavones and flavonols may inhibit monocyte adhesion to the TNF-α-activated endothelium, most likely due to a blockade of expression of functional adhesion molecules down-regulated at the transcriptional level, indicating a definite linkage between the chemical structure of flavonoids and the expression of cell adhesion molecules. Furthermore, the antiathero- genic feature of flavonoids appears to be independent of their antioxidant activity.

혈관내피세포의 세포사멸작용에 대한 (-)Epigallocatechin Gallate의 억제효과

최연정(Yean-Jung Choi),최정숙(Jung-Suk Choi),이세희(Se-Hee Lee),이용진(Yong-Jin Lee),강정숙(Jung-Sook Kang),강영희(Young-Hee Kang) 한국식품영양과학회 2002 한국식품영양과학회지 Vol.31 No.4

본 연구에서는 free radicals의 산화적인 손상에 의한 세포사멸에 있어서 녹차성분의 하나인 (-)epigallocatechin gallate의 억제효과를 규명하였다. 우선 radicals 소거작용에 있어서 (-)epigallocatechin gallate는 탁월한 항산화력을 발휘하였다. 혈관손상과 직결되는 혈관내피세포를 이용하여 hydroxyl radical의 H₂O₂에 의한 산화적인 손상을 유발시켜 세포생존율을 조사하였는데, (-)epigallocatechin gallate는 100 μM 이하의 농도에서는 그 자체 독성이 없었고 H₂O₂의 산화적 독성효과를 경감시키는 것으로 나타났다. 그러나 flavone인 apigenin은 고농도에서 독성을 가지며 radical 소거활성이 미약하고 H₂O₂의 산화독성은 경감시키지 못하였다. 다양한 세포사멸 검출법을 이용하여 세포 및 세포핵의 형태학적 양상을 조사한 결과, 0.25mM H₂O₂에 의한 24시간 이내의 세포죽음은 세포사멸현상에 의하여 초래되었다. 그러나 이러한 세포사멸과정을 겪고 있는 혈관내피세포에 50 μM (-)epigallocatechin gallate를 처리한 경우에 세포핵의 응축이나 DNA fragmentation은 사라지고 세포사멸작용을 억제시키는 효과를 보여주었다. 예상한 바와 같이 apigenin의 flavone은 세포사멸 억제효과를 나타내지 못하였다. (-)Epigallocatechin gallate는 녹차에 함유된 catechins의 하나로서 free radicals의 산화적 손상에 의한 세포사멸에 있어서 탁월한 방어적인 세포생리학적인 기능을 지니고 있으며, 혈관노화 및 혈관손상과 함께 유발되는 세포사멸성 심혈관 질환의 예방과 치료에 기능성 식품 신소재로서 활용될 수 있으리라 본다. Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion scenarios. Oxidative injury can induce cellular and nuclear damages that result in apoptotic cell death. We tested the hypothesis that the catechin flavonoid of (-)epigallocatechin gallate, a green tea polyphenol, inhibits hydrogen peroxide (H₂O₂)-induced apoptosis in human umbilical vein endothelial cells. The effect of apigenin, a flavone found in citrus fruits, on apoptosis parameters was also examined. A 30 min pulse treatment with 0.25 mM H₂O₂ decreased endothelial cell viability within 24 hrs by>30%; this was associated with nuclear condensation and biochemical DNA damage consistent with programmed cell death. In the 0.25 mM H₂O₂ apoptosis model, 50 μM (-)epigallocatechin gallate markedly increased cell viability with a reduction in the nuclear condensation and DNA fragmentation. In contrast, equimicromolar apigenin increased cell loss with intense DNA laddering, positive nick-end labeling and Hoechst 33258 staining. Thus, polyphenolic (-)epigallocatechin gallate, but not apigenin flavone, qualify as an antioxidant in apoptosis models caused by oxidative stress. Further work is necessary for elucidating the antiapoptotic mechanisms of polyphenolic catechins.

`99 정기총회(定期總會) 및 한(韓),일(日) 학술대회(學術大會) : 21세기(世紀) 패션비전 ; Poster 발표(發表) : 수출증대(輸出增大)를 위(爲)한 디자인 개발(開發)(1) -남미지역(南美地域)을 중심(中心)으로-

최연정 ( Yean Jung Choi ) 한국패션비즈니스학회 1999 패션 비즈니스 Vol.3 No.1

Attenuation of monocyte adhesion and oxidised LDL uptake in luteolin-treated human endothelial cells exposed to oxidised LDL

Jeong, Yu-Jin,Choi, Yean-Jung,Choi, Jung-Suk,Kwon, Hyang-Mi,Kang, Sang-Wook,Bae, Ji-Young,Lee, Sang-Soo,Kang, Jung-Sook,Han, Seoung Jun,Kang, Young-Hee Cambridge University Press 2007 The British journal of nutrition Vol.97 No.3

<P>Oxidative modification of LDL is causally involved in the development of atherosclerosis and occurs <I>in vivo</I> in the blood as well as within the vascular wall. The present study attempted to explore whether polyphenolic flavonoids influence monocyte-endothelium interaction and lectin-like oxidised LDL receptor 1 (LOX-1) expression involved in the early development of atherosclerosis. The flavones luteolin and apigenin inhibited THP-1 cell adhesion onto oxidised LDL-activated human umbilical vein endothelial cells (HUVEC), while the flavanols of ( − )epigallocatechin gallate and (+)catechin, the flavonols of quercetin and rutin, and the flavanones of naringin, naringenin, hesperidin and hesperetin did not have such effects. Consistently, Western blot analysis revealed that the flavones at 25 μm dramatically and significantly abolished HUVEC expression of vascular cell adhesion molecule-1 and E-selectin evidently enhanced by oxidised LDL; these inhibitory effects were exerted by drastically down regulating mRNA levels of these cell adhesion molecules. In addition, quercetin and luteolin significantly attenuated expression of LOX-1 protein up regulated in oxidised LDL-activated HUVEC with a fall in transcriptional mRNA levels of LOX-1. In addition, quercetin and luteolin clearly blunted oxidised LDL uptake by HUVEC treated with oxidised LDL. The results demonstrate that the flavones luteolin and apigenin as well as quercetin were effective in the different initial steps of atherosclerosis process by inhibiting oxidised LDL-induced endothelial monocyte adhesion and/or oxidised LDL uptake. Therefore, certain flavonoids qualify as anti-atherogenic agents in LDL systems, which may have implications for strategies attenuating endothelial dysfunction-related atherosclerosis.</P>

대식세포에서 지단백 산화에 대한 수용성 Chitinous Compounds의 항산화 효과에 대한 연구

이세희(Lee Se-Hee),박성희(Park Sung-Hee),이용진(Lee Yong-Jin),윤정한(Jung Han Yoon),최연정(Choi Yean Jung),최정숙(Choi Jung-Suk),강영희(Kang Young-Hee) 韓國營養學會 2003 Journal of Nutrition and Health Vol.36 No.9