• Polymer Science and Technology
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• v.15 no.4
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• pp.422-429
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• 2004

헤파린은 설페이트화된 선형의 Polysaccharide로 이루어져 있으며, 주로 uronic acid로 구성되어 있다. 헤파린은 다양한 구조의 혼합체로서 항혈전성, 염증억제, 신규혈관형성 암 성장 억제 및 면역 억제 등의 다양한 성질을 가지고 있다.(중략)

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.47-49
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• 2003

• Journal of Life Science
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• v.33 no.9
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• pp.703-712
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• 2023

Angiogenesis, the formation of blood vessels from pre-existing vessels, is a multistep process regulated by modulators of angiogenesis. It is essential for various physiological processes, such as embryonic development, chronic inflammation, and wound repair. Dysregulation of angiogenesis causes many diseases, such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. However, the number of effective anti-angiogenic drugs is limited. Recent research has focused on identifying potential drug candidates from natural sources. For example, marine natural products have been shown to have anti-cancer, anti-oxidant, anti-inflammatory, antiviral, and wound-healing effects. Thus, this study aimed to describe the angiogenesis inhibitory effect of Hizikia fusiforms (brown algae) extract. The hexane extract of H. fusiformis has shown inhibitory effects on in vitro angiogenesis assays, such as cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). The hexane extract of H. fusiformis (HFH) inhibited in vivo angiogenesis in a mouse Matrigel gel plug assay. In addition, the protein expression of vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal kinase, and AKT serine/threonine kinase 1 decreased following treatment with H. fusiformis extracts. Our results demonstrated that the hexane extract of H. fusiformis (HFH) inhibits angiogenesis in vitro and in vivo.

• Journal of Life Science
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• v.27 no.1
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• pp.78-88
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• 2017

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

• Journal of Life Science
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• v.19 no.7
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• pp.976-982
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• 2009

Little is known about the cardiovascular roles of alliin, a functional component in garlic that has been used as food material. Thus, we examined a broad range of cardiovascular activities of alliin in this study. From our in vitro experiments, alliin was determined to act as a stimulant to induce endothelial cell proliferation and endothelial cell migration. Since endothelial cell proliferation and migration are highly associated with angiogenesis and wound healing, alliin is suggested as a regulator to control angiogenesis and wound healing. In addition, alliin was elucidated to prevent lipopolysaccharide (LPS)-induced adhesion of THP-1 leukocytes to endothelial cells and LPS-induced homotypic THP-1 cell aggregation. These inhibitory effects indicate that alliin is likely to act as an anti-atherosclerotic and anti-thrombotic factor, because leukocytic adhesion to endothelial cells and homotypic leukocyte aggregation are highly associated with atherosclerosis and thrombosis, respectively. Our additional findings show that alliin has no effect on the production of nitric oxide (NO), an important vasoregulator. In conclusion, alliin is suggested as a regulator for controlling various cardiovascular functions.

• KSBB Journal
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• v.24 no.2
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• pp.122-130
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• 2009

Anti-angiogenic mechanism was examined for anti-obesity agents with the extract of P.radix, P.semen, S.hebra and C.furctus through anti-cell adhesion effect and western blot. Cell adhesion molecules, VCAM-1 was supressed with the order of P.radix (0.2 ppm, 125%) > P.semen (0.5 ppm, 100%) > S.hebra (5.0 ppm, 114%) > C. furctus (5.0 ppm, 111.8%), ICAM-1 was inhibited by P.radix (0.25 ppm, 130%) > P.semen (0.5 ppm, 100%) > S.hebra (5.0 ppm, 138%) > C. furctus (5.0 ppm, 66.7%), E-Selectin was also supressed P.radix (0.25 ppm, 100%) > P.semen (1.0 ppm, 128%) > S.hebra (5.0 ppm, 120%) > C. furctus (5.0 ppm, 100.7%). And signal molecules, VE-cadherin was supressed by P.radix and S.hebra, ${\beta}$-catenin was inhibited by P.radix, and Akt was supressed all these 4 kinds of natural products. These P.radix, P.semen, S.hebra and C.furctus were showed the possibility of anti-obesity agents based on anti-angiogenesis.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.895-903
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• 2005

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated under pathological conditions or by extracellular stimuli, and the regulation of TSP-1 gene expression is important for developing new approaches in tumor therapy. Mistletoe is a parasitir plant that have been used for immunomodulation and antitumor therapy. Helixor A is an aqueous part of mistletoes extract. Here we showed that TSP-1 expression was significantly induced at both mRNA and protein levels in the Hepatocarcinorna cell line (Hep3B) and primary bovine endothelial cell line (BAE) exposed to Helixor A. Our promoter analysis confirmed that the expression of TSP-1 gene was regulated by Helixor A at the transcriptional level. In cell invasion assay, the conditioned media obtained from treatment of these cells significantly reduced the number of invasive cells and also inhibited capillary-like tube formation of BAE cells on Matrigel. Moreover, the inhibitory efforts of the conditioned media on cell invasion and tube formation were reversed by blocking with anti-TSP-1 neutralizing antibodies, suggesting that TSP-1 is involved in Helixor A-indured antiangiogenic effect. Taken together, our results suggest that Helixor A have an antiangiogenic effects through upregulation of TSP-1.

• Korean Journal of Environmental Biology
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• v.28 no.1
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• pp.8-13
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• 2010

This study aimed the role of gold nanoparticles (AuNP) in advanced glycation end-products (AGEs) induced migration and invasion in bovine retinal endothelial cells (BRECs). BRECs were isolated from the retina. Cell viability was confirmed by the MTT assay. In vitro wound migration assay was performed to investigate the migration of BRECs. In vitro tube formation was measured by on-gel system. Apoptosis induced by AuNP was confirmed by caspase-3 assay. AGE-bovine serum albumin (BSA) demonstrated increase of cell migration and proliferation in BRECs. In addition, AuNP regardless of the existence of AGE-BSA suppressed proliferation, migration, and angiogenesis. AuNP suppressed AGE-BSA induced migration and invasion, and induced apoptosis through caspase-3. As a results, AuNP have a potential anti-angiogenic effect for AGE-induced angiogenesis in vitro and offer possibility for the treatment of diabetic retinopathy.

• Proceedings of the Korean Society of Community Living Science Conference
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• 2009.09a
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• pp.83-83
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• 2009

암을 제외한 대부분의 성인병은 혈액순환과 관련된 혈관계 질환들로 이들에 의한 사망 비율의 합은 암의 비율과 비슷하게 나타나 혈관계 질환의 심각성을 나타내고 있다. 혈전에 의한 혈관계 질환은 혈전용해제와 트롬빈저해제를 이용하여 치료하고 예방할 수 있으며, a-glucosidase 저해제는 당뇨병 예방과 치료에 이용할 수 있다. 예로부터 민간요법에서 다양하게 이용되어 왔던 반하를 성인병 치료와 예방에 관련된 기능성식품의 자료로 사용하기 위해 반하 열수추출물을 유기 용매로 분획화하고 분획물의 혈전용해활성, 트롬빈저해활성, 혈당강하효과를 측정하였다. 혈전을 직접 용해하는 활성을 측정하기위해 100 mg/ml의 농도로 준비한 시료액을 fibrin plate 방법을 이용하여 혈전용해활성을 측정 결과 hexane 층, chloroform 층, ethyl acetate 층, butanol 층에서는 활성을 나타내지 않았지만 물 층에서 만 0.8 plasmin unit의 높은 혈전용해활성을 나타냈다. 혈전의 형성을 억제하기위해 혈전형성의 필수 효소인 트롬빈의 활성을 저해하는 트롬빈저해활성을 측정하기위해 10 배 희석한 (10 mg/ml) 시료 용액을 이용하여 트롬빈저해활성을 측정결과 hexane 층에서 75.3%의 높은 트롬빈저해활성을 나타냈으며, ethyl acetate 층과 chloroform에서도 각각 43.3%와 39.7%의 활성을 나타냈다. 또한 탄수화물의 소화를 지연시킴으로서 소장에서 포도당의 흡수를 억제하여 혈관내 당의 농도를 조절하는 혈당강하제의 개발을 위해 준비된 조효소액(10 mg/ml)을 이용하여 a-glucosidase 저해활성을 측정한 결과 ethyl acetate 층과 hexane 층에서 각각 24.9%와 23.4%의 저해활성을 확인하였다. 따라서 반하의 hexane 층과 ethyl acetate 층과 물층은 혈전관련 혈관계 질환과 당뇨병 관련 기능성 식품의 개발 소재로 이용할 수 있을 것으로 기대된다. 특히 최근 질병 치료에 효과는 크지만 부작용이 동반되는 화학약품들 대신 활성은 조금 뒤지지만 부작용이 없는 생약을 이용하려는 경향이 커지고 있다. 따라서 오랫동안 민간용법에서 사용되고 있는 반하는 안정성이 확인된 장점을 갖고 있어, 식품재료나 기능성 음료에 이용할 경우 장기간 섭취가 가능해 혈관계 질환의 치료와 예방에 큰 효과를 가져 올 수 있을 것으로 기대된다.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.