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      Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells

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      https://www.riss.kr/link?id=A82679164

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      다국어 초록 (Multilingual Abstract)

      Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on H<sub>2</sub>O<sub>2</sub>-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.
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      Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxyg...

      Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on H<sub>2</sub>O<sub>2</sub>-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

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      목차 (Table of Contents)

      • INTRODUCTION
      • MATERIALS AND METHODS
      • RESULTS
      • DISCUSSION
      • ACKNOWLEDGEMENTS
      • INTRODUCTION
      • MATERIALS AND METHODS
      • RESULTS
      • DISCUSSION
      • ACKNOWLEDGEMENTS
      • REFERENCES
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      참고문헌 (Reference)

      1 남기열, "홍삼과 백삼의 비교 고찰" 고려인삼학회 29 (29): 1-18, 2005

      2 양승준, "고온고압처리에 의한 인삼의 성분 변화" 한국식품과학회 38 (38): 521-525, 2006

      3 이종원, "고려홍삼으로부터 분리한 수용성 갈변물질의 항산화 활성" 고려인삼학회 29 (29): 44-48, 2005

      4 Lee SK, "Water soluble browning pigments of Korean red ginseng (Panax ginseng C.A. Meyer)" 19 : 244-248, 1995

      5 "Uncaria rhynchophylla induces heme oxygenase-1 as a cytoprotective effect in RAW 264.7 macrophages" 대한독성 유전단백체 학회 6 (6): 33-40, 2010

      6 Kwok HH, "The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status" 48 : 437-445, 2010

      7 Nakajima S, "The effects of ginseng radix rubra on human vascular endothelial cells" 26 : 365-373, 1998

      8 Ip JH, "Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation" 15 : 1667-1687, 1990

      9 Young-Joon Surh, "Role of Nrf2-Mediated Heme Oxygenase-1 Upregulation in Adaptive Survival Response to Nitrosative Stress" 대한약학회 32 (32): 1163-1176, 2009

      10 He F, "Protective effects of ginsenoside Rb1 on human umbilical vein endothelial cells in vitro" 50 : 314-320, 2007

      1 남기열, "홍삼과 백삼의 비교 고찰" 고려인삼학회 29 (29): 1-18, 2005

      2 양승준, "고온고압처리에 의한 인삼의 성분 변화" 한국식품과학회 38 (38): 521-525, 2006

      3 이종원, "고려홍삼으로부터 분리한 수용성 갈변물질의 항산화 활성" 고려인삼학회 29 (29): 44-48, 2005

      4 Lee SK, "Water soluble browning pigments of Korean red ginseng (Panax ginseng C.A. Meyer)" 19 : 244-248, 1995

      5 "Uncaria rhynchophylla induces heme oxygenase-1 as a cytoprotective effect in RAW 264.7 macrophages" 대한독성 유전단백체 학회 6 (6): 33-40, 2010

      6 Kwok HH, "The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status" 48 : 437-445, 2010

      7 Nakajima S, "The effects of ginseng radix rubra on human vascular endothelial cells" 26 : 365-373, 1998

      8 Ip JH, "Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation" 15 : 1667-1687, 1990

      9 Young-Joon Surh, "Role of Nrf2-Mediated Heme Oxygenase-1 Upregulation in Adaptive Survival Response to Nitrosative Stress" 대한약학회 32 (32): 1163-1176, 2009

      10 He F, "Protective effects of ginsenoside Rb1 on human umbilical vein endothelial cells in vitro" 50 : 314-320, 2007

      11 Kobayashi M, "Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation" 7 : 385-394, 2005

      12 Gozzelino R, "Mechanisms of cell protection by heme oxygenase-1" 50 : 323-354, 2010

      13 Lee HJ, "Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats" 58 (58): 1170-1177, 2009

      14 McCoubrey WK Jr, "Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3" 247 : 725-732, 1997

      15 Lee SH, "Identification of Atherosclerosis Related Gene Expression Profiles by Treatment of Benzo(a)pyrene in Human Umbilical Vein Endothelial Cells" 대한독성 유전단백체 학회 5 (5): 113-119, 2009

      16 Idriss NK, "Hemoxygenase-1 in cardiovascular disease" 52 : 971-978, 2008

      17 Deshane J, "Heme oxygenase-1 expression in disease states" 52 : 273-284, 2005

      18 Pae HO, "Heme oxygenase-1 and carbon monoxide: emerging therapeutic targets in inflammation and allergy" 2 : 159-165, 2008

      19 Kim YM, "Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities" MARY ANN LIEBERT INC 14 (14): 137-167, 2011

      20 Leung KW, "Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells" 281 : 36280-36288, 2006

      21 Hien TT, "Ginsenoside Rg3 inhibits tumor necrosis factor-alpha-induced expression of cell adhesion molecules in human endothelial cells" 65 : 699-701, 2010

      22 Hwang YP, "Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells" ACADEMIC PRESS INC ELSEVIER SCIENCE 242 (242): 18-28, 2010

      23 Deramaudt BM, "Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis" 68 : 121-127, 1998

      24 Kim YK, "Free radical scavenging activity of red ginseng aqueous extracts" 172 : 149-156, 2002

      25 Aoki M, "Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: antiapoptotic effect of antioxidant agents on endothelial cells" 38 : 48-55, 2001

      26 Sung J, "Effects of red ginseng upon vascular endothelial function in patients with essential hypertension" 28 : 205-216, 2000

      27 Jovanovski E, "Effects of Korean red ginseng (Panax ginseng C.A. Mayer) and its isolated ginsenosides and polysaccharides on arterial stiffness in healthy individuals" 23 : 469-472, 2010

      28 Terry CM, "Effect of tumor necrosis factor-alpha and interleukin-1 alpha on heme oxygenase-1 expression in human endothelial cells" 274 (274): H883-H891, 1998

      29 Jeon BH, "Effect of Korean red ginseng on blood pressure and nitric oxide production" 21 : 1095-1100, 2000

      30 Kim CS, "Effect of Korea red ginseng on cerebral blood flow and superoxide production" 23 : 1152-1156, 2002

      31 Maines MD, "Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible" 261 : 411-419, 1986

      32 Sumpio BE, "Cells in focus: endothelial cell" 34 : 1508-1512, 2002

      33 Durante W, "Carbon monoxide and vascular cell function (review)" 2 : 255-262, 1998

      34 Baranano DE, "Biliverdin reductase: a major physiologic cytoprotectant" 99 : 16093-16098, 2002

      35 Wong VK, "Asian ginseng extract inhibits in vitro and in vivo growth of mouse lewis lung carcinoma via modulation of ERK-p53 and NF-κB signaling" 111 : 899-910, 2010

      36 Jin YR, "Antithrombotic and antiplatelet activities of Korean red ginseng extract" BLACKWELL PUBLISHING 100 (100): 170-175, 2007

      37 Byung-Jae Park, "Anti-oxidative effects of Phellinus linteus and red ginseng extracts on oxidative stress-induced DNA damage" 한국생화학분자생물학회 42 (42): 500-505, 2009

      38 Kwak YS, "Anti-hyperlipidemic effects of red ginseng acidic polysaccharide from Korean red ginseng" 33 : 468-472, 2010

      39 Park YS, "Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase" 27 : 1319-1325, 2007

      40 Park SH, "A formulated red ginseng extract rescues PC12 cells from PCB-induced oxidative cell death through Nrf2-mediated upregulation of heme oxygenase-1 and glutamate cysteine ligase" 273 : 131-139, 2010

      41 Min JK, "20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway" 349 : 987-994, 2006

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