• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.61-77
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum(Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CC14), D-galactosamine (DGal) and Bacillus Calmette-Guerin(BCG) plus lipopolysaccharides(LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts(AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-l (ICAM-1) and vascular cell adhesion molecule-l (VCAM-1) induced by ox-LDL and AGE.

• Biomolecules & Therapeutics
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• 제9권3호
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• pp.156-161
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• 2001

Inflammation is a frequent radiation-induced 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 bioflavonoid rutin inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Rutin also inhibited ${\gamma}$IR induced production of NO. These data suggest that rutin has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• Archives of Pharmacal Research
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• 제24권5호
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• pp.466-471
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• 2001

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 (VCAM-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, interioring with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that high mannronic acid-containing alginate (HMA) inhibits $\gamma$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose dependent manner. HMA also inhibited $\gamma$IR induced production of Nitric oxide (NO). These data suggest that HMA has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• BMB Reports
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• 제45권3호
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• pp.200-205
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• 2012

Enzymatic oxidation of commercially available pyrogallol was efficiently transformed to an oxidative product, purpurogallin. Purpurogallin plays an important role in inhibiting glutathione S-transferase, xanthine oxidase, catechol O-methyltransferase activities and is effective in the cell protection of several cell types. However, the anti-inflammatory functions of purpurogallin are not well studied. Here, we determined the effects of purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatory responses. The results showed that purpurogallin inhibited LPS-mediated barrier hyper-permeability, monocyte adhesion and migration and such inhibitory effects were significantly correlated with the inhibitory functions of purpurogallin on LPS-mediated cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) releases from HUVECs were inhibited by purpurogallin. Given these results, purpurogallin showed its anti-inflammatory activities and could be a candidate as a therapeutic agent for various systemic inflammatory diseases.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.157-162
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• 2011

Vascular inflammation process has been suggested to be an important risk factor in the development of atherosclerosis. Recently we reported that induction of peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) selectively inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-${\alpha}$-activated human umbilical vein endothelial cells (HUVEC). In this study, we investigated whether genipin inhibits expression of cellular adhesion molecules, which is relevant to inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS) production and expression of VCAM-1, but not ICAM-1 in TNF-${\alpha}$-activated HUVEC. Genipin dose- and time-dependently increased PPAR-${\gamma}$ expression and inhibited TNF-${\alpha}$-induced phosphorylation of Akt and PKC with different degrees. Finally, genipin prevented TNF-${\alpha}$-induced adhesion of U937 monocytic cells to HUVEC. Taken together, these results indicate that upregualtion of PPAR-${\gamma}$ by genipin selectively inhibits TNF-${\alpha}$-induced expression of VCAM-1, in which regulation of Akt and/or PKC play a key role. We concluded that genipin can be used for the treatment of cardiovascular disorders such as atherosclerosis.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.229-234
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• 2015

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-${\alpha}$ for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogenactivated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM ($0.01{\sim}100{\mu}g/mL$) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-${\alpha}$ (3 ng/mL), and it dose dependently prevented the TNF-${\alpha}$ -induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-${\alpha}$ -induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-${\alpha}$ -induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

• 대한본초학회지
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• 제33권4호
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• pp.59-67
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• 2018

Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named "Donguibogam" and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-${\alpha}$ by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-${\alpha}$-induced HUVEC. OJS suppressed TNF-${\alpha}$-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-${\alpha}$-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of $I{\kappa}B-{\alpha}$ in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-${\kappa}B$ p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

• 동의생리병리학회지
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• 제23권4호
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• pp.872-882
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• 2009

Sachil-Tang (SCT) has been traditionally used as a prescription of spasm of the esophagus by stress, pectoralgia and oppressive feeling of the chest in Oriental medicine. This study was carried out to investigate the antioxidant activities of the ethanol extract of SCT and its inhibitory effect on intracellular oxidation and vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells (HUVECs) using various methods. The SCT extract showed a strong inhibitory effect on free radical generating model systems, including DPPH radical, superoxide anions, hydroxyl radical, peroxynirite and nitric oxide. Besides, the SCT extract exhibited a strong inhibitory effect on lipid peroxidation in rat liver homogenate induced by $FeCl_2$-ascorbic acid, and protected plasmid DNA against the strand breakage in a Fenton's reaction system. The SCT extract also inhibited copper-mediated oxidation of human low-density lipoprotein (LDL), and repressed relative electrophoretic mobility of LDL. Furthermore, the SCT extract protected intracellular oxidation induced by various free radical generators and inhibited expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. These results suggest that SCT can be an effective natural antioxidant and a possible medicine of atherosclerosis.

• 생명과학회지
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• 제17권8호통권88호
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• pp.1152-1156
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• 2007

본 실험은 동백꽃의 효능을 알아보기 위하여, 동백꽃을 에틸알콜로써 추출한 후 극성이 다른 다양한 유기용매로 분획하여 나온 fraction으로 신생혈관생성 억제, cell cytotoxity, 세포부착분자에 대한 기능을 ELISA, westen blot 등으로 조사하였다. 신생혈관생성 억제 효과는 특히butanol 층에서 70.2%로 가장 높았으며, acetone층이 54.2%, 그리고 ethylacetate층이 37.0%, chloroform층이 21.2%로 유의성 있는 억제효과가 있었다. 특히 동백꽃의 butanol층은 신생혈관생성억제제로서 좋은 효과가 있는 것으로 판단된다. 그리고, 추출물의 농도별로 cell cytotoxity를 조사한 결과 농도가 200 ug/ml 이하에서 세포독성은 나타나지 않았다. Cell adhesion 저해율은 추출물의 농도 200 μg/mL 에서 ICAM-1은 52.9%, VCAM-1은 62.5%, 그리고 E-selectin은 35.7%로 나타났으며 동백꽃의 추출물의 성분 증가에 따라 발현이 감소됨으로써 cell adhesion을 저해하는 것으로 확인되었다. Westen blot 에서 첨가한 동백꽃 추출물의 농도가 높아질수록 신호전달분자의 발현이 약해지는 것을 관찰할 수 있었다. 따라서 신호전달 분자는 동백꽃 추출물에 의해서 신호전달이 차단되며, NF-KB를 억제함으로서 신생혈관생성을 저해하는 것으로 확인되었다. 따라서 동백꽃 추출물은 항암제 및 항비만제제로서 유용할 것으로 판단된다.