• Korean Journal of Food Science and Technology
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• v.28 no.5
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• pp.850-858
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• 1996

Green tea leaves 12.5 g were extracted twice with 500 ml boiling water. The green tea extract (GTE) contained 4.67 mg solid. The GTE contained polyphenols sush as 54.12% (-) epicatechin gallate, 26.21% (-) epicatechin, 10.71% epicatechin gallate, 7.09% (-) epicatechin and 1.85% catechin. The GTE inhibited the copper-catalyzed oxidation of human LDL at the concentrations of 50 and $100\;{\mu}g/ml$ GTE in the presence of $5\;{\mu}M$ $CuSO_{4}$. The electrophoretic mobility of the LDL oxidized in the presence of $5\;{\mu}M\;CuSO_{4}$ was higher than that of the native LDL. The GTE also inhibited LDL oxidation induced by J774, human monocyte-derived macrophages and vascular endotherial cells. The LDL modified by copper or cells was inhibited by human macrophages at a much greater rate than native LDL in the presence of GTE. The GTE was found to be a potent inhibitor of modification of LDL. GTE inhibited the uptake of cell-modified $^(125)I-labelled$ LDL by macrophages. The formation of conjugated dienes was strongly inhibited in the presence of 50 or $100\;{\mu}g/ml$ GTE.

• Nutrition Research and Practice
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• v.18 no.2
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• pp.194-209
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• 2024

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

• Journal of Animal Science and Technology
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• v.63 no.5
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• pp.1034-1063
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• 2021

The experiment was designed as a 3 × 3 × 2 factorial arrangement of treatments, including (i) pomegranate peel (zero, 4%, and 8 percent), (ii) oxidized soybean oil (zero, 2%, and 4 percent), and (iii) alpha-tocopherol (zero and 200 mg/kg). Supplementation of 8% pomegranate peel in diets significantly decreased the growth performance of broiler chickens. The supplementation of 4% oxidized oil in diets significantly reduced body weight gain and Feed intake whole experimental period (p < 0.05). The results showed that supplementation of 4% pomegranate peel in the diet was associated with low aspartate transaminase (AST), alanine transaminase, and malondialdehyde (MDA). However, 4% pomegranate peel increased the total antioxidant capacity (TAC) and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. The supplemental 4% oxidized oil increased the serum AST, alanine aminotransferase (ALT), and MDA concentrations. TAC, SOD, and Catalase (CAT) activities were affected by 4% oxidized oil and alpha-tocopherol. The use of oxidized oil and vitamin E decreased MDA concentration. The serum glucose and globulin concentrations were significantly lower in the 8% pomegranate peel. The results showed that supplementation with 4% pomegranate peel in diets reduced serum low-density lipoprotein (LDL). The inclusion of 4% oxidized oil in diets reduced serum glucose and increased the blood lipid concentration such as triglyceride, cholesterol and LDL. Vitamin E supplementation reduced the serum cholesterol and LDL concentrations. The use of 8% pomegranate peel reduced red blood cell (RBC), hemoglobin, and packed cell value (PCV). The results indicated that supplementation with 8% pomegranate peel and 4% oxidized oil in diets decreased the immunoglobulin concentration in broilers. In addition, it was found that the inclusion of 4% pomegranate peel in diets resulted in higher IgG, IgM and total immunoglobulin. Pomegranate peel supplementation significantly decreased meat MDA concentration. Supplementation of 4% oxidized oil increased MDA of meat (p < 0.05). Vitamin E supplementation (200 mg/kg) significantly decreased MDA of meat (p < 0.05). Consequently, the results of this experiment showed that supplementation with 4% pomegranate peel had beneficial effects on broiler chickens. It was also found that feeding 2% oxidized oil in diets had no adverse effect on broilers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.3
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• pp.402-408
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• 1994

Human plasma low density lipoprotein (LDL) is the major factor of coronary heart disease.But recent studies suggest the normal LDL can be realdily oxidized by oxygen free radicals and not interact with LDL receptors.Lipoprotei particles consist of lipid and protein, and fatty acids are prone to oxidatioin.The fatty acid compositions of LDL from Koreans was compared with that of Westerners.From the results, the raio of unsaturated fatty acids of korean and Westerner approximately 30 and 70%, respectively.which means Westerners are more labile in the lipid oxidation of LDL than Koreams.Normal LDL was incubated with $CuSO_4$ in PBS to lead for the peroxidation of LDL, and it was tested by the detection of TBARS and free radicals.Then, ascorbate, ${\alpha}-tocopherol$ and hyaluronic acid were found to have effects of antioxidants on LDL oxidation.The amount of free radical increased as the extent of oxidation increased.The time course of free radical formation was similar to TBARS.Therefore, determination of free radical by Luminometer was much more convenient than that of TBARS.

• 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.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.23-33
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• 2011

Objectives : The present study investigated effects of Artemisia Capillaris Thunberg ethanol extract(EtOH ext). on lowering lipid, anti-oxidation and concentration of plasma inflammatory mediators using rat fed on high oxidized fat. Methods : We divided fat sprague-dawley rats fed on high oxidized into 4 groups. They were normal group, feed with 100 mg/kg Artemisia Capillaris Thunberg group, feed with 200 mg/kg Artemisia Capillaris Thunberg group and feed with 300 mg/kg Artemisia capilaris Thunberg group. They were administered for 4 weeks. We measured concentration of plasma free fatty acid(FFA), plasma triglyceride, plasma total cholesterol, and plasma low density lipoprotein-cholesterol(LDL-cholesterol), plasma high density lipoprotein-cholesterol(HDL-cholesterol), concentration of liver total cholesterol and liver triglyceride (TG), concentration of plasma thiobarbituric acid reactive substance(TBARS) and liver thiobarbituric acid reactive substance(TBARS), glutathione peroxidase (GSH-Px) activity, superoxide dismutase(SOD) activity and catalase(CAT) activity, plasma nitric oxide(NO), ceruloplasmin and ${\alpha}-glycoprotein$. Results : 1. The Artemisia Capillaris Thunberg EtOH ext. groups showed low concentration of plasma FFA, plasma triglyceride, plasma total cholesterol and plasma LDL-cholesterol compared to control group. However, concentration of plasma HDL-cholesterol was increased in the Artemisia Capillaris Thunberg EtOH ext. groups. 2. Concentration of liver total cholesterol and liver TG showed a significantly decrement in all Artemisia Capillaris Thunberg EtOH ext. groups than that of control group. 3. The Artemisia Capillaris Thunberg EtOH ext. groups showed lower values in concentration of plasma TBARS and liver TBARS than that of control group. The values of GSH-Px activity, SOD activity and CAT activity were increased in the Artemisia Capillaris Thunberg EtOH ext. groups. 4. The values of plasma NO, ceruloplasmin and ${\alpha}-glycoprotein$ were decreased in Artemisia Capillaris Thunberg EtOH ext. groups. Conclusions : Based on the results in this study, the Artemisia Capillaris Thunberg EtOH ext. showed a positive effect in lowering lipid, anti-oxidation and decrement of plasma inflammatory mediators.

• Biomedical Science Letters
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• v.26 no.3
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• pp.164-169
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• 2020

Atherosclerosis is a cardiovascular disease in which plaque builds up inside of an artery and can lead to various complications such as myocardial infarction, stroke, and thrombosis. Recently, hypertriglyceridemia has attracted significant attention as contributors to development of atherosclerosis. However, molecular mechanism of its contribution to atherosclerosis is poorly understood. Here we proposed a potential link between triglyceride (TG) and atherosclerosis. TG treatment promoted downregulation of certain scavenger receptor, macrophage scavenger receptor-1 (MSR-1) in phorbol myristate acetate (PMA)-derived human macrophages. TG treatment caused reduction of MSR-1 mRNA expression in a time- and dose-dependent manner. Using chemical inhibitors, we found that inhibition of signaling pathways associated with PI3K and PLC enhances TG-induced reduction of MSR-1 expression in THP-1 macrophages implying that PI3K and PLC is implicated in the expression of MSR-1 in macrophages. Since MSR-1 is associated with uptake and clearance of atherogenic lipoprotein, oxidized low density lipoprotein (oxi-LDL), our data suggest that increase of oxi-LDL due to TG-mediated reduction of its receptor MSR-1 can promote atherosclerosis.

• Korean Journal of Pharmacognosy
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• v.35 no.3 s.138
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• pp.233-238
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• 2004

Lipoprotein-associated phospholipase $A_2\;(Lp-PLA_2)$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. Also acyl-CoA: cholesterol acyltransferase (ACAT) and oxidized low-density lipoprotein (LDL) playa key role in atherosclerosis, respectively. And so, the inhibitory activities of the methanol extracts of 42 insect resources were examined on $Lp-PLA_2$, ACAT, and LDL oxidation for screening of anti-atherogenic substances. Among them, the methanol extracts of Eurydema rugosa significantly inhibited all of upper three activities. Several kinds of tested insects having high inhibitory effect with the methanol extracts were extracted with n-hexane, ethyl acetate, and acetone, and their inhibitory activities were tested.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.2
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• pp.113-124
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• 2012

The oxidative modification of low density lipoprotein(LDL) has been implicated in the development of atherosclerosis. Oxidized LDL(oxLDL) is captured into macrophage and stimulates to form macrophage foam cell. And it can induce an inflammation and smooth muscle proliferation in atherosclerotic plaque. Objective : In this study, we aimed to investigate the effect of Bupleuri radix(SH) on the foam cell formation, a critical initiation stage of atherosclerosis. Methods : To achieve the goal, we examined the effect of SH on LDL oxidation, nitric oxide production in RAW264.7, and the effect of SH on cupuric sulfate-induced cytotoxicity, LDH release, and macrophage activity. Results : SH inhibited the formation of oxidized LDL from native LDL in RAW264.7 cell culture, and decreased the release of LDH from cupric sulfate-stimulated RAW264.7 cell. In other experiments, SH activated RAW264.7 cell, and prolonged the survival time, and inhibited foam cell formation induced by oxLDL in Raw 264.7 cells. Conclusion : These results showed that SH might prevent atherosclerosis by controlling the early stages of foam cell formation.