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      Hot Water Extract of Scutellaria baicalensis Inhibits Migration, Invasion and Tube Formation in a Human Umbilical Vein Endothelial Cell Model and a Rat Aortic Ring Sprouting Model

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      https://www.riss.kr/link?id=A101742410

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      국문 초록 (Abstract)

      혈관신생의 억제는 암과 같은 신생혈관형성 질환의 치료를 위해 유용한 접근법이다. 신생혈관형성의 핵심인자인 혈관내피세포성장인자는 신생혈관형성 질환의 치료를 위한 주요한 표적이다. 그러므로, 본 연구에서는 in vitro 분석과 ex vivo 동물 실험을 통해 황금 열수추출물의 신생혈관형성 억제효과를 연구했다. 본 연구결과에서 황금 열수추출물이 혈관내피세포성장인자에 의해 자극된 혈관내피세포에 있어 세포독성 없이 세포의 이동, 침투, 관형성을 농도 의존적으로 억제하였다. 더 나아가 황금 열수추출물은 혈관내피세포성장인자에 의해 유도된 흰쥐 대동맥 주변 미세혈관 발아를 예방하였다. 본 연구결과들은 황금 열수추출물이 신생혈관형성 억제작용이 있고, 이는 혈관내피세포성장인자에 의해 유도된 혈관신생을 억제 하는 잠재적 소재가 될 수 있음을 제안한다.
      번역하기

      혈관신생의 억제는 암과 같은 신생혈관형성 질환의 치료를 위해 유용한 접근법이다. 신생혈관형성의 핵심인자인 혈관내피세포성장인자는 신생혈관형성 질환의 치료를 위한 주요한 표적이...

      혈관신생의 억제는 암과 같은 신생혈관형성 질환의 치료를 위해 유용한 접근법이다. 신생혈관형성의 핵심인자인 혈관내피세포성장인자는 신생혈관형성 질환의 치료를 위한 주요한 표적이다. 그러므로, 본 연구에서는 in vitro 분석과 ex vivo 동물 실험을 통해 황금 열수추출물의 신생혈관형성 억제효과를 연구했다. 본 연구결과에서 황금 열수추출물이 혈관내피세포성장인자에 의해 자극된 혈관내피세포에 있어 세포독성 없이 세포의 이동, 침투, 관형성을 농도 의존적으로 억제하였다. 더 나아가 황금 열수추출물은 혈관내피세포성장인자에 의해 유도된 흰쥐 대동맥 주변 미세혈관 발아를 예방하였다. 본 연구결과들은 황금 열수추출물이 신생혈관형성 억제작용이 있고, 이는 혈관내피세포성장인자에 의해 유도된 혈관신생을 억제 하는 잠재적 소재가 될 수 있음을 제안한다.

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      다국어 초록 (Multilingual Abstract)

      Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neovascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.
      번역하기

      Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an a...

      Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neovascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

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      목차 (Table of Contents)

      • Introduction
      • Materials and Methods
      • Results
      • Discussion
      • References
      • Introduction
      • Materials and Methods
      • Results
      • Discussion
      • References
      • 초록
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      참고문헌 (Reference)

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      1 Fas, S. C., "Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis" 108 : 3700-3706, 2006

      2 Dvorak, H. F, "Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy" 20 : 4368-4380, 2002

      3 Karkkainen, M. J., "Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymph angiogenesis" 19 : 5598-5605, 2000

      4 Holmes, K., "Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition" 19 : 2003-2012, 2007

      5 Bernatchez, P. N., "Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent" 274 : 31047-31054, 1999

      6 Rousseau, S., "Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase" 275 : 10661-10672, 2000

      7 Ferrara, N, "Vascular endothelial growth factor" 29 : 789-791, 2009

      8 Olsson, A. K., "VEGF receptor signalling - in control of vascular function" 7 : 359-371, 2006

      9 Molassiotis, A., "Use of complementary and alternative medicine in cancer patients: A European survey" 16 : 655-663, 2005

      10 Ishimaru, K., "Two flavone 2'-glucosides from Scutellaria baicalensis" 40 : 279-281, 1995

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      12 Milanowski, J., "Treatment of non-small cell lung cancer-where we are?" 81 : 55-60, 2013

      13 Huang, K. L., "Therapeutic effects of baicalin on lipopolysaccharide-induced acute lung injury in rats" 36 : 301-311, 2008

      14 Thakker, G. D., "The role of phosphatidylinositol 3-kinase in vascular endothelial growth factor signaling" 274 : 10002-10007, 1999

      15 Liao, H. L., "Synthesis and anticancer activities of 5, 6, 7-trimethylbaicalein derivatives" 52 : 1162-1165, 2004

      16 Chi, Y. S., "Suppression of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix" 72 : 59-66, 2005

      17 Zachary, I., "Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family" 49 : 568-581, 2001

      18 Koch, S., "Signal transduction by vascular endothelial growth factor receptors" 437 : 169-183, 2011

      19 Waisundara, V. Y., "Scutellaria baicalensis: enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic wistar rats" 36 : 517-540, 2008

      20 Shin, J. W., "Scutellaria baicalensis attenuates blood-brain barrier disruption after intracerebral hemorrhage in rats" 40 : 85-96, 2012

      21 Huan, S. K., "Scutellaria baicalensis alleviates cantharidin-induced rat hemorrhagic cystitis through inhibition of cyclooxygenase-2 overexpression" 17 : 6277-6289, 2012

      22 Ye, F., "Quality evaluation of commercial extracts of Scutellaria baicalensis" 49 : 217-222, 2004

      23 Błach-Olszewska, Z., "Production of cytokines and stimulation of resistance to viral infection in human leukocytes by Scutellaria baicalensis flavones" 28 : 571-581, 2008

      24 Li-Weber, M., "New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents wogonin, baicalein and baicalin" 35 : 57-68, 2009

      25 Singh, M., "New strategies in cancer chemoprevention by phytochemicals" 4 : 426-452, 2012

      26 Sagar, S. M., "Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer - Part 1" 13 : 14-26, 2006

      27 Bruno, M., "Natural and hemisynthetic neoclerodane diterpenoids from scutellaria and their antifeedant activity" 19 : 357-378, 2002

      28 Yang, J., "NMDA receptor-mediated neuroprotective effect of the Scutellaria baicalensis Georgi extract on the excitotoxic neuronal cell death in primary rat cortical cell cultures" 2014

      29 Tan, A. C., "Molecular pathways for cancer chemoprevention by dietary phytochemicals" 63 : 495-505, 2011

      30 Bussolino, F., "Molecular mechanisms of blood vessel formation" 22 : 251-256, 1997

      31 Huang, S. M., "Molecular Inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade" 1 : 507-514, 2002

      32 Risau, W, "Mechanisms of angiogenesis" 386 : 671-674, 1997

      33 Park, K. I., "Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in human lung cancer cells" 133 : 634-641, 2011

      34 Park, H. S., "Korean Scutellaria baicalensis Georgi methanol extracts inhibits metastasis via the Forkhead Box M1 activity in hepatocellular carcinoma cells" 155 : 847-851, 2014

      35 Murphy, D. A., "Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006)" 169 : 1875-1885, 2006

      36 Wahl, O., "Inhibition of tumor angiogenesis by antibodies, synthetic smallmolecules and natural products" 18 : 3136-3155, 2011

      37 Zhang, D. Y., "Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis" 63 : 4037-4043, 2003

      38 Huang, D., "Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo" 68 : 81-88, 2008

      39 Park, H. J., "Induction of quinone reductase by a methanol extract of Scutellaria baicalensis and its flavonoids in murine Hepa 1c1c7 cells" 7 : 465-471, 1998

      40 Lee, I. S., "Hepatoprotective activity of scutellariae radix extract in mice fed a high fat diet with chronic alcohol exposure" 25 : 1348-1353, 2011

      41 Valko, M., "Free radicals and antioxidants in normal physiological functions and human disease" 39 : 44-84, 2007

      42 Pedram, A., "Extracellular signal-regulated protein kinase/Jun kinase cross-talk underlies vascular endothelial cell growth factorinduced endothelial cell proliferation" 273 : 26722-22678, 1998

      43 Himeji, M., "Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell" 245 : 269-274, 2007

      44 Fan, T. P., "Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy" 16 : 57-66, 1995

      45 Harvey, K., "Comparative analysis of in vitro angiogenic activities of endothelial cells of heterogeneous origin" 63 : 316-326, 2002

      46 Wang, C. Z., "Commonly used antioxidant botanicals: active constituents and their potential role in cardiovascular illness" 35 : 543-558, 2007

      47 Zhang, H., "Chinese medicine injection shuanghuanglian for treatment of acute upper respiratory tract infection:a systematic review of randomized controlled trials" 2013

      48 Bonham, M., "Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma" 11 : 3905-3914, 2005

      49 Wang, C. Z., "Botanical flavonoids on coronary heart disease" 39 : 661-671, 2011

      50 Lin, Y. T., "Baicalein induces apoptosis in SCC-4 human tongue cancer cells via a Ca2+-dependent mitochondrial pathway" 21 : 1053-1058, 2007

      51 Rajput, S., "Antitumor promoting potential of selected phytochemicals derived from spices: a review" 21 : 205-215, 2012

      52 Ikemoto, S., "Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines" 55 : 951-955, 2000

      53 Lee, J. J., "Antithrombotic and antiplatelet activities of Soshiho-tang extract" 137-, 2013

      54 Huang, W. H., "Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI" 70 : 2371-2380, 2006

      55 Scheck, A. C., "Anticancer activity of extracts derived from the mature roots of S.Scutellaria baicalensis on human malignant brain tumor cells" 16 : 27-, 2006

      56 Ye, F., "Anticancer activity of Scutellaria baicalensis and its potential mechanism" 8 : 567-572, 2002

      57 Yoon, S. B., "Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages" 125 : 286-290, 2009

      58 Kim, E. H., "Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling molecules" 126 : 320-331, 2009

      59 Ho, F. M., "Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes" 142 : 175-187, 2012

      60 Carmeliet, P., "Angiogenesis in cancer and other diseases" 407 : 249-257, 2000

      61 Zhang, N., "A herbal composition of Scutellaria baicalensis and Eleutherococcus senticosus shows potent anti-inflammatory effects in an ex vivo human mucosal tissue model" 2012

      62 Yun, J., "A Scutellaria baicalensis radix water extract inhibits morphine-induced conditioned place preference" 52 : 1382-1387, 2014

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      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-08-03 학술지명변경 외국어명 : Korean Journal of Life Science -> Journal of Life Science KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
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      2016 0.37 0.37 0.42
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