• 동의생리병리학회지
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• 제24권5호
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• pp.822-826
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• 2010

In order to validate the use of Faeces Trogopterori as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of F. Trogopterori (EFT) on the production of monocyte chemoattractant protein-1 (MCP-1), of which chemokine stimulates the migration of mononuclear cells, in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-alpha. The extract inhibited dose-dependently MCP-1 production without its cytotoxic effect on HUVECs, as measured by enzyme-linked immunosorbent assay, and significantly decreased mRNA levels of MCP-1, as determined using reverse transcription polymerase chain reaction. These results suggest that F. Trogopterori may have therapeutic potential in the control of endothelial disorders caused by inflammation.

• BMB Reports
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• 제46권11호
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• pp.544-549
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• 2013

High mobility group box 1 (HMGB1) is involved in the pathogenesis of vascular diseases. Unlike activated protein C (APC), the activation of PAR-1 by thrombin is known to elicit proinflammatory responses. To determine whether the occupancy of EPCR by the Gla-domain of APC is responsible for the PAR-1-dependent antiinflammatory activity of the protease, we pretreated HUVECs with the PC zymogen and then activated PAR-1 with thrombin. It was found that thrombin downregulates the HMGB1-mediated induction of both TNF-${\alpha}$ and IL-6 and inhibits the activation of both p38 MAPK and NF-${\kappa}B$ in HUVECs pretreated with PC. Furthermore, thrombin inhibited HMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion molecules in HUVECs if EPCR was occupied. Collectively, these results suggest the concept that thrombin can initiate proinflammatory responses in vascular endothelial cells through the activation of PAR-1 may not hold true for normal vessels expressing EPCR under in vivo conditions.

• BMB Reports
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• 제43권9호
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• pp.604-608
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• 2010

Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) mediates proinflammatory responses in primary human umbilical vein endothelial cells (HUVECs), and it upregulates the expression of secretory group IIA phospholipase $A_2$ ($sPLA_2$-IIA). $sPLA_2$-IIA plays a pivotal role in inflammation, and antithrombin (AT) possesses properties that are beneficial to endothelial cells. Therefore, we investigated the effects of AT on the expression of $sPLA_2$-IIA in TNF-$\alpha$-stimulated HUVECs. TNF-$\alpha$ potently upregulated the expression of $sPLA_2$-IIA, and prior treatment of cells with AT inhibited the expression of $sPLA_2$-IIA in HUVECs. Also, antibodies or siRNA for syndecan-4 blocked the protective effect of AT. Furthermore, PI3-kinase and the AKT pathway are significantly involved in the AT-mediated inhibition of the expression of $sPLA_2$-IIA. These results show that AT effectively suppresses the upregulated $sPLA_2$-IIA expression, which might contribute to the cytoprotective effects of AT in the treatment of severe inflammatory diseases.

• Korean Journal of Acupuncture
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• 제25권1호
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• pp.113-130
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• 2008

Objectives : Hyangsapyungwisan (HPS) has been used for treatment of cardiovascular diseases including of arthralgia, myalgia in traditional Korean medicine. However, the medical actions of HPS have not been clearly investigated. The aim of this study was to elucidate the antiradical and antioxidant activity of the extract for herb-acupuncture (HPS-HA) obtained from HPS. Methods & Results : HPS-HA exhibited a stronger inhibition rate (55.5%) on lipid peroxidation of rat liver homogenate induced by $FeCl_2$-ascorbic acid. In addition, HPS-HA markedly interfered with hydroxylradical generation through iron ions chelating action. While pro-oxidant effect of HPS-HA was nearly undetectable at concentrations of 0.5-10㎎/mL. Moerover, HPS-HA revealed a potent antiradical activities on 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radicals, superoxide anions, nitric oxide and peroxynitrite. Furthermore, HPS-HA inhibited copper- and AAPH-mediated oxidation of human low-density lipoprotein (LDL), and also suppressed the relative electrophoretic mobility of LDL. HPS-HA showed strong protective activity against oxidative damage of HUVECs induced by SIN-1. Conclusions : These results suggest that HPS-HA may be effective in protecting against oxidative diseases.

• Journal of Applied Biological Chemistry
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• 제50권4호
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• pp.249-253
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• 2007

Thirteen edible plants previously reported to show inhibitory activities on farnesyl protein transferase (FPTase) and phosphatase of the regenerating liver-3 (PRL-3) were evaluated for inhibitory activity on the proliferation of human umbilical vein endothelial cells (HUVECs). Four plant extracts, Oenothera erythrosepala, Perilla frutescens, Panicum miliaceum, and Quercus acutissima, significantly inhibited the proliferation of HUVECs induced by the basic fibroblast growth factor (bFGF) without cytotoxicity at 100 ${\mu}g/mL$. Myristica fragrans, Rosmarinus officinalis, and Syringa patula also showed inhibitory activity on the proliferation with only mild cytotoxicity.

• Journal of Ginseng Research
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• 제38권1호
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• pp.34-39
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• 2014

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other ${\alpha},{\beta}$-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an ${\alpha},{\beta}$-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin Vepropidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

• 한국축산식품학회지
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• 제44권1호
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• pp.216-224
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• 2024

The reduction of nitric oxide (NO) bioavailability in the endothelium induces endothelial dysfunction, contributing to the development of hypertension. Although Lactobacillus consumption decreases blood pressure, intracellular signaling pathways related to hypertension have not been well elucidated. Thus, this study examined the effect of spray-dried Lactiplantibacillus plantarum K79 (LpK79) on NO production, intracellular signaling pathways, and inflammatory responses related to vascular function and hypertension. NO production was assessed in human umbilical vein endothelial cells (HUVECs) treated with LpK79. Endothelial NO synthase (eNOS) and intracellular signaling molecules were determined using Western blot analysis. LpK79 dose-dependently increased NO production and activated eNOS via the phosphoinositide 3-kinase/Akt signaling pathway HUVECs. Moreover, LpK79 mitigated the activation of crucial factors pivotal for vascular contraction in smooth muscle cells, such as phospholipase Cγ, myosin phosphatase target subunit 1, and Rho-associated kinase 2. When HUVECs were treated with LpL79 in the presence of Escherichia coli lipopolysaccharide (LPS), LpK79 effectively suppressed mRNA and protein expression of pro-inflammatory mediators induced by E. coli LPS. These results suggest that LpK79 provided a beneficial effect on the regulation of vascular endothelial function.

• 한국식품영양과학회지
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• 제39권12호
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• pp.1753-1760
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• 2010

혈관내피세포는 만성적인 고혈당 상태에 노출되면, 반응성 산소기의 급격한 증가로 인해 산화스트레스를 일으키게 된다. 이를 보호하기 위해 사용되는 항산화제는 혈관내피세포의 생존율을 높이며 2차적인 질병의 유발을 감소 및 완화시켜서 당뇨합병증에 도움이 되는 것으로 알려져 있는데, 본 연구에서는 항산화 효과가 있는 것으로 알려진 조릿대잎 추출물을 이용하여 고농도의 포도당으로 유도된 산화스트레스에 대한 혈관내피세포의 보호효과를 조사하고자 하였다. 즉, 30 mM 포도당에 노출되어 산화적 스트레스가 유발된 HUVECs에 조릿대잎 추출물 ethyl acetate(ESLE) 층을 분주한 결과, 농도 의존적으로 세포 생존율이 증가하였고, 활성산소종 수준과 지질과산화물 가는 ESLE 첨가에 의해 유의적으로 감소하는 것을 확인할 수 있었다. 또한 고농도 포도당으로 GSH 함량과 SOD, GSH-px, catalase 등과 같은 항산화효소의 활성이 감소된 HUVECs에 ESLE를 분주하였을 때 이들의 함량 및 활성이 유의적으로 증가되었으며, western blotting을 통해 ESLE 첨가가 SOD와 catalase 발현을 증가시킴을 확인할 수 있었다. 따라서 ESLE는 혈관내피세포에서 고농도 포도당으로 인해 유발된 산화적 스트레스에 대해 세포를 보호하는 효과가 있는 것으로 나타났으며, 이는 ESLE가 세포내 활성산소종을 감소시키고 항산화효소계의 활성을 증가시킴으로써 산화스트레스를 감소시킨 결과에 기인하는 것으로 사료되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4369-4376
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• 2015

Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma.

• Journal of Yeungnam Medical Science
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• 제25권1호
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• pp.41-49
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• 2008

한탄바이러스가 혈소판활성인자 활성에 영향을 미치는지 알아보기 위하여 간접적으로 혈소판활성인자 수용체의 발현과 분해효소의 활성을 측정하였다. 혈관내피세포에서 혈소판활성인자 수용체의 유전자를 역전사 중합효소연쇄반응으로, 단백질은 western blot으로 측정하였다. 또한 세포표면에 발현된 혈소판활성인자 수용체의 양은 FACS로 분석하였다. 한탄바이러스에 감염된 혈관내피세포에서 혈소판활성인자 수용체의 유전자, 단백질, 세포 표면의 발현 모두 바이러스에 감염되지 않은 대조 세포보다 감염 후 2, 3일째 증가 하였다. 혈액 내 혈소판활성인자 분해효소의 활성을 비교한 결과 신증후출혈열 환자에서 정상인에 비하여 2.5배 낮았다. 그리고 신증후출혈열 환자가 회복됨에 따라 혈소판활성인자의 활성이 다시 정상 수준으로 회복되는 것으로 나타났다. 따라서 한탄바이러스에 의해 증가된 혈소판활성인자 수용체의 발현이 혈소판활성인자와 혈관내피세포와 반응성을 증가시키고, 신증후출혈열 환자 혈액에서 감소된 혈소판활성인자 분해효소가 혈소판활성인자의 분해를 지연 시켜 작용시간을 증가 시킴으로써 과다한 혈소판활성인자의 생물학적 작용이 신증후출혈열의 병리현상을 초래할 것으로 사료된다.