• 생약학회지
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• 제45권1호
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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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• 제13권4호
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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.

• 대한방사선치료학회지
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• 제14권1호
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• pp.165-174
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• 2002

혈관내피세포 성장 인자(Vascular endothelial growth factor, VEGF)는 혈관내피세포 특이하게 성장요인으로 작용하는 물질로 알려져 있다. 전리방사선에 대한 혈관내피세포의 효과는 정상조직에 대한 반응에 있어 아주 중요한 요소일 것으로 생각된다. 본 연구는 방사선 조사에 의해 배양시킨 혈관내피세포에서 apoptosis가 유도되는지, 유도가 된다면 VEGF에 의해 apoptosis가 억제되는지 그리고 apoptosis의 억제가 어떤 경로를 경유하는지를 실험하였다. 혈관내피세포에 방사선를 조사한 결과, 대조군에 비하여 선량이 증가함에 따라 apoptosis가 증가하였다. 같은 조건하에서 VEGF는 농도 의존적으로 apoptosis를 억제하였다. Antiapoptotic factor로서 VEGF가 어떤 신호 과정을 경유하는지를 밝히고자, 혈관내피세포에 방사선을 조사하여 apoptosis를 유도하면서 Flt-1과 Flk-1/KDR receptor를 처리하였다. 그결과 VEGF에 유도된 apoptosis 억제효과가 차단되었다. Phosphatidylinositol 3'-kinase(PI3-kinase) 특정 억제 물질인 Wortmanin과 LY294002를 방사선 조사한 혈관내피에 VEGF와 함께 처리했을 때 VEGF에 의해 유도된 apoptosis를 억제하였다. 이같은 결과는 VEGF가 방사선 조사로 일어나는 세포 치사를 억제하는 중요한 역할을 담당하며, In Vivo의 실험이 더 이루어져야 할 것으로 생각된다.

• Nutrition Research and Practice
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• 제5권5호
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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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• 제40권2호
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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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• 제17권7호
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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.

• 대한본초학회지
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• 제26권3호
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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.

• 한국해양바이오학회지
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• 제1권3호
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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.

• 생명과학회지
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• 제27권9호
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• pp.1059-1063
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• 2017

혈관신생과정은 종양 형성과 이동에 필수적인 과정으로 촉진제와 저해제에 의하여 조절되며, 이러한 혈관신생과정의 저해는 새로운 항암치료 기법으로 이용하고 있다. 최근, 한약재와 식료품으로부터 추출한 천연물을 새로운 치료 물질로 널리 이용하고 있으며, 실제 in vitro 뿐만 아니라 in vivo 상에서도 항암 효과가 나타나는 것을 확인하였다. 그 중 도라지는 아시아에서 한약재와 식료품으로 오랫동안 사용 되어왔다. 본 연구에서는 도라지 추출물이 in vitro 상에서 인간 제대 정맥 내피 세포의 혈관신생을 억제하는 효과에 대해 조사하였다. 도라지 추출물은 세포독성 없이, 혈관 형성 및 이동, 침윤 현상을 모두 억제하는 효과를 보였다. 특히, 세포 이동은 80% 정도 감소 시켰으며 침윤 현상이 거의 나타나지 않는 것을 확인하였다. 이러한 결과를 토대로 도라지 추출물은 혈관신생 억제제로 이용할 수 있으며, 더 나아가 항암제로 개발될 수 있을 것이라 사료된다.

• KSBB Journal
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• 제18권1호
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• pp.25-29
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• 2003

더덕의 메탄올 추출물(CL-ex)이 혈관신생에 영향을 주는 지의 여부를 알아보기 위하여, 인간태반 정맥내피세포와 돼지 폐동맥내피세포를 이용하여 실험하였다. 실험 결과, 더덕추출물은 FGF에 의해 유도된 시험관 내 혈관신생을 억제하였다. 또한 더덕추출물은 내피세포의 DNA 합성에는 영향을 주지 않았으나, FGF에 의해 증가된 내피세포의 이동을 농도 의존적으로 강하게 억제하였고, MMPs의 분비 역시 감소시켰다. 이러한 결과에 의하면, 더덕에 함유된 혈관신생 억제 물질은 혈관내피세포의 이동 과정에 작용하여 그 효과를 나타내는 것이라 추정된다. 따라서 더덕은 그 발생과 진행이 혈관신생에 의존하고 있는 것으로 알려진 암 등의 질병 예방과 치료를 위한 유용한 식물자원으로 개발될 수 있음을 시사한다.