• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.28-34
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• 2014

Rhei Rhizoma (RR) and Moutan cortex (MC) have been reported to have anti-inflammatory effects. However, little is known about the effects of RR and MC on endothelial inflammation and insulin resistance (IR). This study aims to investigate whether the water extracts of RR and MC could exert protection against palmitic acid (PA)-induced inflammation and IR in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 6 h with RR or MC, and then exposed to PA for 24 h. The levels of interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were determined by enzyme-linked immunosorbant assay kits. Western blot analysis was performed for activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and insulin receptor substrate-1 (IRS-1). In HUVECs stimulated with PA, both RR and MC significantly inhibited the production of TNF-${\alpha}$ and IL-6 and the activation of NF-${\kappa}B$. At the same concentrations, the inhibitory effects of RR were more potent than those of MC. PA reduced insulin-induced phosphorylation of IRS-1, which was reversed by RR and MC. The results suggest that RR and MC are effective in inhibiting PA-associated endothelial inflammation and ameliorating IR by beneficial regulation of NF-${\kappa}B$ and IRS-1 activation.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.4
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• pp.301-307
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• 2009

Inflammatory processes of vascular endothelial cells play a key role in the development ofatherosclerosis. We determined the anti-inflammatory effects and mechanisms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on LPS-treated human umbilical vein endothelial cells (HUVECs) to evaluate their cardioproteerive potential. Cells were pretreated with DHA, EPA, or troglitazone prior to activation with LPS. Expression of COX-2, prostaglandin $E_2$ ($PGE_2$) and IL-6 production, and $NF-{\kappa}B$ activity were measured by Western blot, ELISA, and luciferase activity, respectively. Results showed that EPA, DHA, or troglitazone significantly reduced COX-2 expression, $NF-{\kappa}B$ luciferase activity, and $PGE_2$ and IL-6 production in a dose-dependent fashion. Interestingly, low doses (10 ${\mu}$M) of DHA and EPA, but not troglitozone, significantly increased the activity of $NF-{\kappa}B$ in resting HUVECs. Our study suggests that while DHA, EPA, and troglitazone may be protective on HUVECs under inflammatory conditions in a dose-dependent manner. However there may be some negative effects when the concentrations are abnormally low, even in normal endothelium.

• The Journal of Korean Society for Radiation Therapy
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• v.14 no.1
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• pp.165-174
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• 2002

Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we examined the effect of VEGF on radiation induced apoptosis and receptor/second messenger signal transduction pathway for VEGF effect in human umbilical vein endothelial cells (HUVECs). VEGF was found to protect HUVECs against the lethal effects of ionizing radiation by inhibiting the apoptosis induced in these cells by radiation exposure. VEGF (1-30 ng/ml) dose dependently inhibited apoptosis by irradiation. Pre-treatment with Flt-1 and Flk-l/KDR receptor blocked the VEGF-in duced antiapoptotic effect. Phosphatidylinositol 3'-kinase (PI3-kinase) specific inhibitor, Wortman in and LY294002, blocked the VEGF-induced antiapoptotic effect. These data suggest that VEGF may play an important role in survival of HUVECs due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.381-388
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• 2011

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-${\alpha}$-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-${\alpha}$ exposure significantly increased expression of monocyte chemoattractant protein (MCP)-l, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-l and VCAM-l production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-l production. The effects of genistein and daidzein on MCP-l secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-${\alpha}$ exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)${\kappa}$B activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-l and eNOS expression than that of daidzein. Additionally, NF${\kappa}$B transactivation might be partially related to the down-regulation of these mRNAs in TNF-${\alpha}$-stimulated HUVECs.

• Journal of Ginseng Research
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• v.40 no.2
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• pp.151-159
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• 2016

Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3071-3075
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• 2016

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.83-90
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• 2011

Objectives : This study was performed to investigate the influence of black ginseng radix extracts (BG) and ginsenoside Rg3, Rg5 on basic fibroblast growth factor (bFGF) induced proliferation, migration and capillary tubule-like formation of human umbilical vein endothelial cells (HUVECs). Methods : HUVECs were cultured with BG and ginsenoside Rg3, Rg5 at different concentrations (60, 125, 250, 500, $1,000{\mu}g/m\ell$) for 2 day In the presence of bFGF, respectively. XTT was used to detect the proliferation. Migration and tube formations were examined to detect the antiangiogenesis. Also, the chick embryo chorioallantoic membrane (CAM) assay was performed to detect the antiangiogenesis. Results : BG and ginsenoside Rg3, Rg5 significantly inhibited bFGF-induced endothelial cell proliferation and migration in a dose-dependent manner. Tube formation in bFGF-induced HUVECs were suppressed by BG and ginsenoside Rg3, Rg5. Moreover, BG and ginsenoside Rg3, Rg5 (30-$50{\mu}g$/egg) inhibited new blood vessel formation on the growing CAM. Conclusions:Based on the present results, it can be suggested that BG has a potential chemopreventive agent via antiangiogenesis.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.3
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Journal of Life Science
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• v.27 no.9
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• pp.1059-1063
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• 2017

Angiogenesis is an essential step in tumoral growth and metastasis and is regulated by a balance between stimulators and inhibitors. Recently, antiangiogenic target therapy has shown promise as a new type of chemotherapy. Natural products have attracted widespread attention worldwide as a useful source of novel therapeutic compounds. The balloon-flower has long been used as a traditional medicinal material and food in Asia. In this study, we investigated whether extract of balloon-flower would inhibit in vitro angiogenesis and vascular-like network formation in human umbilical vein endothelial cells (HUVECs). The extract of Balloon-flower did not affect the viability of HUVECs. However, treatment with the Balloon-flower extract suppressed tube formation of HUVECs. In addition, after treatment with the Balloon-flower extract, cell migration decreased about 80%, and cell invasion was almost completely inhibited. Taken together, these results suggest that extract of Balloon-flower may have potential as an angiogenic inhibitor and that it could be developed as an anticancer agent.

• KSBB Journal
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• v.18 no.1
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• pp.25-29
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• 2003

In this study, we examined the effects of the methanolic extract(CL-ex) of Codonopsis lanceolata on the angiogenesis stimulated with basic fibroblast growth factor(bFGF) in vitro, using porcine pulmonary arterial endothelial cells(PPAECs). In addition, we investigated the endothelial functions involved in angiogenesis, such as proliferation, migration and secretion of matrix metalloproteinases(MMPs), using human umbilical vein endothelial cells(HUVECS). CL-ex inhibited FGF-induced sprout formation in vitro at concentrations of 0.1-100 ug/ml. Although CL-ex did not affect the proliferation of endothelial cells, CL-ex strongly inhibited the FGF-induced migration of HUVECS at concentrations of 0.1-1 ug/ml; the degree of inhibition of endothelial cells by C-ex was 49.4% at 0.1 ug/ml and 71.9 % at 1.0 ug/ml. Moreover, CL-ex inhibited the secretion of MMPs from HUVECS stimulated with FGF. Therefore, the inhibitory effect of CL-ex on angiogenesis in vitro could be explained by the inhibition of endothelial cell migration. From these results, we suggest that Codonopsis lanceolata is a useful herb for the development of therapeutics or preventive food factors for angiogenesis related diseases, such as tumors.