• Journal of Ginseng Research
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• v.48 no.2
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• pp.171-180
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• 2024

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. Results: HUVEC was the more sensitive cell line to the anti-proliferative effects of S-Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S-Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. Conclusion: The combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.

• Journal of Life Science
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• v.23 no.7
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• pp.926-932
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• 2013

Glutamine and serum are essential for cell survival and proliferation in vitro, yet the signaling pathways that sense glutamine and serum levels in endothelial cells remain uninvestigated. In this study, we examined the effects of glutamine deprivation and serum starvation on the fate of endothelial cells using a human umbilical vein endothelial cell (HUVEC) model. Our data indicated that glutamine deprivation and serum starvation trigger a progressive reduction in cell viability through apoptosis induction in HUVECs as determined by DAPI staining and flow cytometry analysis. Although the apoptotic effects were more predominant in the glutamine deprivation condition, both apoptotic actions were associated with an increase in the Bax/Bcl-2 (or Bcl-xL) ratio, down-regulation of the inhibitor of apoptosis protein (IAP) family proteins, activation of caspase activities, and concomitant degradation of poly (ADP-ribose) polymerases. Moreover, down-regulation of the expression of Bid or up-regulation of truncated Bid (tBid) were observed in cells grown under the same conditions, indicating that glutamine deprivation and serum starvation induce the apoptosis of HUVECs through a signaling cascade involving death-receptor-mediated extrinsic pathways, as well as mitochondria-mediated intrinsic caspase pathways. However, apoptosis was not induced in cells grown in glutamine- and serum-free media when compared with cells exposed to glutamine deprivation or serum starvation alone. Taken together, our data indicate that glutamine deprivation and serum starvation suppress cell viability without apoptosis induction in HUVECs.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.406-411
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• 2005

Fermented materials with enterobacteria isolated from fusiform fish, have strong anti-angiogenesis effect and anti-cell adhesion effect. PLM-f74 got from 74th fraction of size exclusion chromatography from fermented material, showed strong anti-cell adhesion effect between HUVECs and U937 monocytic cell. Adhesion of U937 cell to HUVEC stimulated with IL-1b was clearly inhibited by PLM-f74 in a dose-dependent manner by 12.1, 21.2, 50.9, and 78.2%, when U937 cells treated with each of the PLM-f74 and stimulated with PMA (100 mg/L) was added onto untreated and unstimulated HUVECs, adhesion was observed by 15.8, 31.9, 70.8, and 102%, when both cell types were pretreated with PLM-f74, the adhesion was prominently decreased by 83.7, 99.2, 110, and 120.8%, with 0.74, 3.7, 7.4, and 18.5ug/mL of PLM-f74, respectively. PLM-f74, also, reduced IL-1-stimulated HUVEC expression of adhesion molecules, VCAM-1, ICAM-1, and E-selectin dose-dependently by ELISA method.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1132-1138
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• 2009

Vascular inflammation is an important event in the development of vascular diseases such as tumor progression and atherosclerosis. This study was to investigate the inhibitory effects of WK-38, a new herbal prescription for the treatment of atherosclerosis, on vascular inflammation in human umbilical vein endothelial cells (HUVEC). WK-38 is composed of Rhei Rhizoma, Magonoliae Cortex, Moutan Cortez Radicis. Pretreatment with WK-38 was significantly blocked TNF-$\alpha$-induced expression level of cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial cell selectin (E-selectin) in a dose-dependent manner. TNF-$\alpha$-induced cell adhesion in co-cultured U937 and HUVEC was also blocked by pretreatment with WK-38. Moreover, WK-38 significantly suppressed p65 NF-${\kappa}B$ translocation into the nucleus by TNF-$\alpha$ as well as the phosphorylation and degradation of $I{\kappa}B-{\alpha}$. In conclusion, the present data suggested that WK-38 could suppress TNF-$\alpha$-induced vascular inflammatory process, though inhibition of NF-${\kappa}B$ activation in HUVEC.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.145-150
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• 2004

Inflammation is a frequent radiation-induced reaction following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with ${\gamma}$-irradiation (${\gamma}$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell Surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that vitamin C inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Vitamin C a1so inhibited the production of Nitric oxide (NO) induced by ${\gamma}$IR. These data suggest that vitamin C has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.480-494
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• 2018

Objectives: To investigate the effect of fermented extract of Artemisiae Iwayomogii Herba, Curcumae Longae, Crataegi Fructus and Salviae Miltiorrhizae Radix (FMH) on anti-inflammation associated with dyslipidemia and anti-oxidation in RAW264.7 and HUVEC cells. Methods: The total polyphenols, total flavonoids, DPPH radical scavenging activity, ABTS radical scavenging activity, and cytotoxicity of FMH were measured. RAW264.7 cells treated with FMH were tested for production of NO, and for cytokine and LTB4 levels and HUVEC cells treated with FMH were examined for production of cDNA of genes related to inflammation. Results: 1. FMH contained polyphenols and flavonoids. The DPPH and ABTS radical scavenging activity of FMH increased in a concentration-dependent manner. 2. FMH treatment inhibited the production of nitric oxide (NO), cytokines, and LTB4 in RAW264.7 cell when compared to the untreated control group. 3. FMH decreased the transcription of pro-inflammatory genes, whereas it increased transcription of anti-inflammatory genes, in HUVEC cells. Conclusion: FMH is effective as an antioxidant and for treatment and prevention of dyslipidemia, atherosclerosis, ischemic heart disease, stroke, and other cardiocerebrovascular diseases.

• Journal of Haehwa Medicine
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• v.25 no.1
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• pp.71-86
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• 2016

Objective : Hongyi (Formica yessensis) is the dried insect of fomicidae. In previous studies, it appeared possibilities on anti-thrombosis, preventing atherosclerosis, treating rheumatoid disease, and inhibiting hela cell. In this study, we investigated anti-inflammatory effects and mechanism of Hongyi. Methods : Hongyi A was extracted by water and made dried powder. Hongyi B was extracted by ethanol and made dried powder. We measured Nitric Oxide (NO) production on the mouse macrophages (RAW 264.7), mouse vascular endothelial cell (MOVAS) and human vascular endothelial cell (HUVEC) for anti-inflammatory effect. In addition, we conducted reverse transcription reaction (RT-PCR) for investigating the mechanism. Results : In RAW 264.7 macrophages stimulated by LPS, Hongyi A ($100{\mu}g/m{\ell}$) decreased NO production compared with LPS $2{\mu}g/ml$ control group with statistical significance (p<0.05). Hongyi A (50, $100{\mu}g/m{\ell}$) also decreased NO production compared with LPS $4{\mu}g/ml$ control group with statistical significance (p<0.01). Hongyi B (50, $100{\mu}g/m{\ell}$) decreased NO production compared with LPS $2{\mu}g/ml$ control group with statistical significance (p<0.01). Hongyi B (10, 50, $100{\mu}g/m{\ell}$) also decreased NO production compared with LPS $4{\mu}g/ml$ control group with statistical significance (p<0.01, p<0.001, p<0.001). In the MOVAS, Hongyi A and B increased NO production compared with control group. In the HUVEC, Hongyi B increased NO production compared with control group. The expression of NF-${\kappa}B$ in 12-hours MOVAS culture was decreased by Hongyi A and B (10, $50{\mu}g/ml$) compared with control group, but expression of $I{\kappa}B$ was increased. In the 24-hours MOVAS culture, expression of $I{\kappa}B$ was significantly increased. The expression of NF-${\kappa}B$ in 12-hours HUVEC culture was decreased by Hongyi A and B compared with control group, but expression of $I{\kappa}B$ was increased. Hongyi B also increased eNOS mRNA gene expression. Conclusions : Hongyi A and B showed anti-inflammatory effect in mouse macrophages with the activation of vascular endothelial cell through NO production in MOVAS and HUVEC repectively. Honyi B showed superior effect than Hongyi A, but additonal mechanism study should be conducted.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.3
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• pp.379-385
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• 2019

Osteoporosis is a disease that increases the risk of fractures by inducing a decrease in bone strength by the changes in hormones and a decrease in minerals. Recent reports have indicated that the long-term administration of Adefovir dipivoxil (ADV), which is used as a treatment for the hepatitis virus and AIDS, may have osteoporotic side effects. On the other hand, there are few studies on the cytopathic correlation of these causes. In this study, the biological relevance of ADV was evaluated using osteoblast hFOB1.19 and vascular endothelial cell HUVEC. First, the cells were treated with ADV at different concentrations, and DAPI and crystal violet staining were performed for morphological analysis of each cell and nucleus. A CCK-8 assay, real-time PCR, alkaline phosphatase (ALP) staining, and activity was performed to evaluate the drug effects on cell proliferation, gene expression, and osteoblast differentiation. As a result, ADV induced cell hypertrophy in hFOB1.19 cells and HUVEC cells. Furthermore, ADV not only inhibited cell proliferation and TGF-${\beta}$ expression but was also involved in osteoblast differentiation. Overall, these results provide basic data to help better understand the mechanism of ADV-induced osteoporosis and its clinical implications.

• Journal of Yeungnam Medical Science
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• v.27 no.2
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• pp.91-97
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• 2010

Endothelial cells play a key role in pathological processes such as cancer cell metastasis, atherosclerosis, and diabetic retinopathy. Vascular smooth muscle cells directly involve in the formation of atheroma in atherosclerosis. Some kinds of the endothelial cells are simply harvested from the umbilical veins, the tunica intima of aortic walls, the retina using various enzymes solutions. Those purely isolated cells provide a powerful tool in vitro studies of the endothelial cell related diseases. In this context, the cultured smooth muscle cells after the isolation from the tunica media of aortic walls are also used for elucidating the pathogenesis of atherosclerosis. Here, I briefly introduce articles that include the isolation of human umbilical vein endothelial cells(HUVEC), aortic endothelial and smooth muscle cells, retinal microvascular endothelial cells(RMEC), as well as the diseases' applications of these cells.

• Korean Journal of Pharmacognosy
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• v.37 no.4 s.147
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• pp.253-257
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• 2006

We examined anti-angiogenic effects of water extracts from 32 plant materials (20 Korean medicinal plants and 12 western herbs) using cell-based anti-angiogenic assay, HUVEC tube formation assay, and then we found that 7 plant extracts inhibited HUVEC tube formation strongly. The plant materials which showed anti-angiogenic effects are Cinnamomi Ramulus, Atractylodis Rhizoma alba, Polygalae Radix, Myristicae Semen, Artemisiae Iwayomogii Herba, leaves of Rosmarinus officinalis, and leaves of Melissa officinalis. We also investigated inhibitory effects of these anti-angiogenic herbal extracts on MMP (matrix metalloproteinase) activity which has important roles in angiogenesis. Among extracts tested in this study, water extract of Melissa officinalis showed the most potent anti-angiogenic and MMP inhibitory activity.