• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.100-108
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• 2003

The regulation of plasma lipid level, particularly LDL cholesterol, represents the focus of current therapy for atherosclerosis. And $Lp-PLA_2$ is able to hydrolyse oxidized phosphatidylcholine within LDL into lyso-PC and oxidized fatty acids. $Lp-PLA_2$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. We investigated the inhibitory effects of methanol extracts of 224 natural plants on $Lp-PLA_2$ activity. Seven kinds of methanol extracts of tested plants showed above 50% inhibitory effect with the concentration of $100\;{\mu}g/ml$. The concentrated aqueous suspensions of each methanol extract were partitioned with n-hexane, $CHCl_3$, and EtOAc. Among them, EtOAc extracts of Astilbe chinensis var. davidii (root) and Pourthiaea villosa var. brunnea (leaf) significantly inhibited $Lp-PLA_2$ activity at the same concentration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1576-1580
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• 2007

Aralia cordata Thunb. (Araliaceae, ACT) is an remarkable herbal plant that has been widely used in traditional oriental medicine for the treatment of inflammatory diseases and cardiovascular disorders. In this study, we have established a vascular aging model in rats by orally administrating excessive vitamin $D_2$ (500,000 IU/kg/day) for 4 days followed by feeding high cholesterol diet for 16 weeks and then rats were randomly divided into control group, high cholesterol diet (HCD) group, HCD+ACT (30 mg/kg) and HCD+ACT (60 mg/kg) group. ACT (30, 60) significantly reduced total cholesterol (TC) content compared with HCD, but no significant differences in the serum lipids. Secondly, we measured the serum levels of Oxidized Low-dencity Lipoprotein (OxLDL) and malondialdehyde (MDA) in order to further investigate the anti-vascular aging mechanism of ACT. The results, ACT (30, 60) treatments decreased OxLDL, MDA　content　and increased Cu/Zn superoxide dismutase activity compared with HCD treatments. The results suggested that ACT inhibited OxLDL production rather than serum lipids lowering and that ACT could be used as potential anti-atherosclerotic agent in aged cells.

• Journal of Society of Preventive Korean Medicine
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• v.4 no.2
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• pp.205-213
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• 2000

The oxidative modification of low density lipoprotein(LDL) has been implicated in the development of atherosclerosis . Oxidized LDL(oxLDL) are found in macrophage foam cell , and it can induce an macrophage proliferation in atherosclerotic plaque. In this study, we investigated the hypothesis that Tokhwalkisaengtang(TK) may reduce atherosclerosis by lowering the oxidizability of LDL, To achieve this goal, we examined the effect of TK on LDL oxidation, nitric oxide production in murine macrophage cell line , and the effect of TK on cupuric sulfate-induced cytotoxicity. LDH release, and macrophage activity TK inhibited the generation of oxLDL from native LDL in macrophage cell culture, and decreased the release of LDH from cupric sulfate-stimulated macrophage. In other experiments, TK activated macrophase cell, and increased the survival rate, and enhanced nitric oxide production in macrophage.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.1
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• pp.27-32
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• 2009

The effects of oxidized low-density lipoprotein(OxLDL) and its major lipid constituent lysophosphatidylcholine(LPC) on $Ca^{2+}$ entry were investigated in cultured human umbilical endothelial cells(HUVECs) using fura-2 fluorescence and patch-clamp methods. OxLDL or LPC increased intracellular $Ca^{2+}$ concentration($[Ca^{2+}]_i$), and the increase of $[Ca^{2+}]_i$ by OxLDL or by LPC was inhibited by $La^{3+}$ or heparin. LPC failed to increase $[Ca^{2+}]_i$ in the presence of an antioxidant tempol. In addition, store-operated $Ca^{2+}$ entry(SOC), which was evoked by intracellular $Ca^{2+}$ store depletion in $Ca^{2+}$-free solution using the sarcoplasmic reticulum $Ca^{2+}$ pump blocker, 2, 5-di-t-butyl-l,4-benzohydroquinone(BHQ), was further enhanced by OxLDL or by LPC. Increased SOC by OxLDL or by LPC was inhibited by U73122. In voltage-clamped cells, OxLDL or LPC increased $[Ca^{2+}]_i$ and simultaneously activated non-selective cation(NSC) currents. LPC-induced NSC currents were inhibited by 2-APB, $La^{3+}$ or U73122, and NSC currents were not activated by LPC in the presence of tempol. Furthermore, in voltage-clamped HUVECs, OxLDL enhanced SOC and evoked outward currents simultaneously. Clamping intracellular $Ca^{2+}$ to 1 ${\mu}M$ activated large-conductance $Ca^{2+}$-activated $K^+(BK_{ca})$ current spontaneously, and this activated $BK_{ca}$ current was further enhanced by OxLDL or by LPC. From these results, we concluded that OxLDL or its main component LPC activates $Ca^{2+}$-permeable $Ca^{2+}$-activated NSC current and $BK_{ca}$ current simultaneously, thereby increasing SOC.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

• Tuberculosis and Respiratory Diseases
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• v.51 no.3
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• pp.211-223
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• 2001

Background : Rhinovirus infection of the airways results in increased permeability of the airway vascular endothelium with the influx of plasma proteins, including lipids such as LDL. In vitro studies on the effect of oxLDL on leukocytes has shown many pro inflammatory effects on multiple leukocytes. We hypothesized that oxLDL is one mechanism for recruiting granulocytes to the airways during a RV infection. Therefore, chemotaxis and transendothelial migration, in response to nLDL, was determined for these granulocytes. Methods : nLDL was oxidized with 5mM Cu2S04 for 20-24 hours. 3-5 105 cells were loaded into the Transwell filter while the chemotatic agonists were placed in the lower well for chemotaxis. Confluent monolayers on HPMEC were grown on Transwell filters for transendothelial migration. The filters were washed and eosinophils and neutrophils loaded on to the filter with the chemotatic agonist was were placed in the lower well. The wells were incubated for 3 hours. The number of migrating cells was counted on a hemocytometer. Results : OxLDL, but not nLDL, is chemotatic for eosinophils and neutrophils. The level of granulocytes chemotaxis was dependent on both the concentration of LDL and its degree of oxidation. OxLDL stimulates eosinophil and neutrophils migration across HPMEC monolayers (+/-IL-$1{\beta}$ preactivation) in a dose dependent manner. Conclusion : Increased vascular permeability during a RV infection may lead to the influx and oxidation of LDL. The resulting oxLDL. is one possible mechanism for the recruitment of neutrophils and eosinophils to the airway interstitial matrix. Once in the airways, granulocytes can further interact with oxLDL to promote airway inflammation.

• Microbiology and Biotechnology Letters
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• v.25 no.3
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• pp.286-292
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• 1997

This study was undertaken to evaluate an antioxidative activity of silymarin and silybin obtained from Silybum marianum against oxidation of human low density lipoprotein (LDL). The electrophoretic mobility observed apparently was higher phase for LDL oxidized by macrophages compared to native LDL. Silymarin and silybin inhibited the copper-catalysed oxidation of human LDL in a dose-dependent manner. Silymarin and silybin at the concentration of 50 $\mu$M/ml also inhibited the copper catalysed oxidation of LDL induced by the cell J774 and macrophages. LDL reisolated from the cell incubation in the presence of silymarin or silybin was degraded at rates similar with native LDL. Silymarin or silybin found to be potential inhibitors against oxidation of $^{125}$I-LDL by macrophages and endothelial cells.

• Journal of Life Science
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• v.14 no.1
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• pp.180-187
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• 2004

Crowing evidence indicates that oxidized low density lipoprotein (LDL) nay promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The effect of geraniin on the susceptibility of human low density lipoprotein (LDL) to macrophages-induced oxidation was investigated by monitoring a thiobarbiruric acid reactive substrance (TBARS). The antioxidative activity of geraniin was higher than that of $\alpha$-tocopherol on low density lipoprotein (LDL) oxidation by thiobarbituric acid reactive substance (TBARS). Geraniin inhibited the C $u^{2+}$ mediated oxidation of human LDL in a dose dependent manner at concentration of 50 and 100 $\mu\textrm{g}$/mL. Geraniin, almost completely inhibited the macrophages mediated LDL oxidation in electrophoretic mobility and conjugate diene of LDL oxidation. Also, geraniin almost completely inhibited 0$_2$$^{[-10]}$ at concentration of 100 $\mu\textrm{g}$/mL. The physiological relevance of the antioxidative activity was validated at the cellular level where geraniin inhibited endothelial cell mediated LDL oxidation, When compound with several other antioxidants geraniin showed a high activity equal to natural antioxidants, $\alpha$-tocopherol and ascorbic acid, and the synthetic antioxidant, protocol. These results indicate that geraniin might play a protective antioxidant effects on LDL, probably affecting both the structural properties of macrophage and endothelial cell for the LDL oxidation..

• Journal of Life Science
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• v.7 no.4
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• pp.289-296
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• 1997

Antioxidative activity of fraction extracted from cultivation of Aspergillus sp. A-5 against oxidation of human low density lipoprotein(LDL) was investigated. Fractions of Aspergillus sp. A-5 cultivation was sucessively purified with ethyl acetate and silica gel column chromatography. The concentration of fraction 4 inhibited Cu$^{2+}$-induced oxidation of LDL almost completely. Band 3 isolated by the further purification of fraction 4 was higher than that of same concentration of $\alpha$-tocopherol, BHA and BHT. The elcetrophoretic mobility of oxidized LDL by addition of Band 3 was faster than that of native LDL, but slower than that of oxidzed LDL. It is concluded that fraction of Aspergillus cultivation contained antioxidants with the capacity to inhibit oxidative modification of LDL.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.