• The Journal of Korean Medicine
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• v.38 no.2
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• pp.53-60
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• 2017

Objectives: Beakdugu-tang (BDGT) consists of three medicinal herbs, and this prescription has long been used in treatment of various digestant problem in Korea. In this study, we designed to clarify mechanisms by which Korean traditional digestive medicine, BDGT, may exert anti-hepatic steatosis effects via improved insulin resistance cell model in human hepatocellular carcinoma (HepG2) and monocyte (THP-1). Materials and methods: The preparation of BDGT and constituents were extracted with 70% ethanol. HepG2 and THP-1 were treated with different concentrations of BDGT and constituents in the presence and absence of stimulants such as free fatty acids (FFAs) and oxidized low-density lipoprotein (ox-LDL), respectively. Results: The BDGT and its constituents inhibited the FFAs-stimulated lipid accumulation in HepG2 cells. Ethanol extracts of Amomum cardamomum (ACE) improved the ox-LDL induced insulin resistance in THP-1 cells. Also, treatment of monocytic cells with ACE increased anti-hepatic steatosis related gene levels including ABCA, ABCG and SR-B1. Conclusion: The results suggest that the ethanol extract of BDGT and its constituents potently inhibit the FFAs- and ox-LDL induced liver steatosis via improved insulin resistance.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• 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 the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1147-1153
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• 2004

The effect of commercial deer antler drink (provided by Chung-yang Deer Farm) on blood glucose level, plasma lipids and antioxidants state in type 2 diabetic patients were studied. Ten patients with type 2 diabetes participated in the study and consumed 2 pouches (200 mL) of deer antler drink every day for 3 weeks. No significant differences were observed in levels of triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). However, oxidized LDL measured as conjugated dienes decreased in the patients after the trial. Plasma tocopherols and carotenoids levels showed no significant changes. No significant differences were observed in erythrocyte SOD, catalase and GSH-Px in the each group. No significant differences were observed in plasma TRAP. The results would suggest that deer antler drink influences conjugated dienes but long-term intervention trial may be necessary to see further beneficial effect of deer antler drink in diabetic patients.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.22.1-22.21
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• 2020

In the progression of atherosclerosis, macrophages are the key immune cells for foam cell formation. During hyperlipidemic condition, phagocytic cells such as monocytes and macrophages uptake oxidized low-density lipoproteins (oxLDLs) accumulated in subintimal space, and lipid droplets are accumulated in their cytosols. In this review, we discussed the characteristics and phenotypic changes of macrophages in atherosclerosis and the effect of cytosolic lipid accumulation on macrophage phenotype. Due to macrophage plasticity, the inflammatory phenotypes triggered by oxLDL can be re-programmed by cytosolic lipid accumulation, showing downregulation of NF-κB activation followed by activation of anti-inflammatory genes, leading to tissue repair and homeostasis. We also discuss about various in vivo and in vitro models for atherosclerosis research and next generation sequencing technologies for foam cell gene expression profiling. Analysis of the phenotypic changes of macrophages during the progression of atherosclerosis with adequate approach may lead to exact understandings of the cellular mechanisms and hint therapeutic targets for the treatment of atherosclerosis.

• Preventive Nutrition and Food Science
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• v.6 no.1
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• pp.51-56
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• 2001

This study was carried out to evaluate whether antioxidant nutrient suppplementation with $\alpha$-tocopherol, vitamin C, $\beta$-carotene, and selenium reduces the lipid peroxide levels and increases the antioxidative enzyme activities in patients with coronary hart disease. Eighty nine patients participated in a randomized, double-blind, placebo-controlled trial. The antioxidant group (45 patients) was given daily doses of $\alpha$-tocopherol (400 IU), vitamin C (50 mg), $\beta$-carotene (15 mg), and selenium (50 $\mu\textrm{g}$) and forty four patients received a placebo. Thirty eight subjects (84.4%) of the antioxidant group and thirty nine subjects (88.6%) of the placebo group completed the three-month supplementation. Serum levels of tocopherol, vitamin C and $\beta$-carotene significantly increased in the antioxidant group compared with the baseline (p<0.05). Thiobarbituric acid-reactive substances(TBARS) decreased significantly (0.6 nmol MDA/mL) in the antioxidant group compared with that (0.09 nmol MDA/mL) in the placebo group (p=0.03). However, antioxidant supplementation did not affect the level of oxidized-LDL measured as autoantibodies against oxidized-LDL. The superoxide dimutase activity in red blood cells increased in the antioxidant group compared with the baseline (p<0.05). However, glutathione peroxidase activities did not change after supplementation in both groups, and catalase activity significantly decreased in the placebo group (p<0.05). These results suggest that antioxidant supplementation for 3 months with $\alpha$-tocopherol, vitamin C, $\beta$-carotene and selenium in patients with coronary heat disease may be partially protective against oxidative stress.

• Korean Journal of Community Nutrition
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• v.13 no.2
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• pp.263-275
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• 2008

Impaired fasting glucose (IFG) is one of significant risk factors of developing diabetes. The persons with IFG are, thus, an important target group for primary prevention of diabetes. It is well known that plasma homocysteine concentration may be increased in poor folate nutritional status. Elevated level of plasma homocysteine is considered as a marker of enhanced oxidative stress. In addition, the protective effect against oxidative stress may be diminished in poor antioxidative nutrient status as vitamin C. It is, therefore, important to maintain adequate nutritional status of folate and vitamin C in the patients with type 2 diabetes or IFG. This study was performed to determine the effects of supplementation of folic acid or vitamin C on plasma concentrations of homocysteine, oxidized LDL, and lipids and on the activity of plasma anti-oxidative enzyme in patients with IFG. A total of 97 patients with IFG were participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folatesupplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A were received 1,000 mg of vitamin C, and those in FA were given 1 mg of folate plus 1,000 mg of vitamin C daily for 4 weeks. No change in plasma concentrations of vitamin C, lipids, and oxidized LDL and the activity of GSH-Px were observed in vitamin C-supplemented group (A + FA) and folate-supplemented group (F + FA) compared to the placebo group (C + A). Only the folate-supplemented group (F + FA) had significantly increased average serum folate concentration and lowered plasma homocysteine concentration compared to the placebo group (C + A). Thus, it should be recommended the patients with IFG to increase folate intake through diets and, if it is not sufficient, to take folic acid supplements to prevent the development of complications induced by hyperhomocysteinemia as well as oxidative stress.

• Journal of Sericultural and Entomological Science
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• v.41 no.3
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• pp.135-140
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• 1999

This study was designed to investigate the effects of mulberry leaf extract (MLE) on oxygen radicals and their scavenger enzymes in serum of rats. Sprague-Dawley (SD) male rats (160${\pm}$10g) were fed experimental diets (MLE-100 and MLE-300 groups) added 100 and 300mg/kg BW/day for 6weeks. Triglyceride (TG) levels were significantly inhibited (10% and 20%) in MLE-100and MLE-300 groups, but there were no significant differences in total, LDL-and HDL- cholesterol levels in both MLE-100 and MLE-300 groups. Hydroxyl radical ($.$OH) formations resulted in a marked decreases(20∼25%) in MLE-100 and MLE-300 groups compared with control group, while superoxide radical (O2.-)and hydrogen peroxide formations resulted in a considerable decreases(7∼10% and 5∼10%) in MLE-100 and MLE-300 groups compared with control group. Lipid peroxide (LPO)and oxidized protein(>C=O group) productions resulted in a significant decreases (10% and 6∼10%) in MLE-100 and MLE-300 groups compared with control group. Superoxide dismutase (SOD)and catalase (CAT) activities were remarkably increased (30% and 40∼55%) in MLE-100 and MLE-300 groups, but glutathione peroxidase (GSHPX) activities were significantly increased (10∼15%) in MLE-100 and MLE-300 groups compared with control group. These results suggest that anti-aging effect of mulberry leaf extract (MLE) may play a pivotal role in attenuating a various agerelated changes.

• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.109-126
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• 2009

Objectives: To investigate the effects of Chrysanthemum indicum L. pharmacopuncture on lipids, antioxidant capacity and anti-inflammation in rats fed high-fat diet. Methods: Hyperlipidemic rats induced by high-fat diet were divided into 5 groups: no treatment control (normal, n=8), high-fat diet only control (control, n=8), high-fat diet and Chrysanthemum indicum L. pharmacopuncture at CV4 group (TI, n=8), high-fat diet and Chrysanthemum indicum L. pharmacopuncture at CV17 group (TII, n=8), and high-fat diet and Chrysanthemum indicum L. pharmacopuncture at EX-HN3 group (TIII, n=8). They were given pharmacopuncture accordingly every other day for two weeks followed by analyses of lowering lipids effects, oxidative capacity and anti-inflammatory effects. Results: Compared with the control, pharmacopuncture groups showed significantly decreased plasma total cholesterol (TC), liver thiobarbituric acid reactive substance (TBARS), catalase, glutathione peroxidase, neutrophils, monocytes, plasma and liver IL-$1{\beta}$, and plasma and liver IL-6. In other parameters including plasma and liver triglyceride, liver TC, LDL-cholesterol, HDL-cholesterol, liver TBARS, supraoxide dismutase, total protein, albumin, blood cell analysis, plasma and liver TNF-$\alpha$, and IL-10, there was no significant difference between control and pharmacopuncture groups. No clear acupoint-specificity was observed. Conclusions: Chrysanthemum indicum L. pharmacopuncture may improve control of hyperlipidemia.

• Korean Journal of Acupuncture
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• v.25 no.1
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• pp.139-154
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• 2008

Objectives & Methods : The purpose of this study is to observe the anti-oxidative effects of electroacupuncture to Yinlingquan(SP9) in AAPH induced oxidative stress of rats. The author performed several experimental items including measurements of body weight, levels of albumin, total bilirubin, LDL-cholesterol, GOT and GPT in serum, levels of SOD, glutathione, catalase, NO and MDA in liver, histological analysis of liver. The conclusions are as follows. Results : 1. In the SP9-EA group, the level of LDL-cholesterol was significantly decreased in comparison with that of the holder group and control group. 2. In the SP9-EA group, SOD activity, glutathione concentration in liver were increased, and NO concentration was decreased significantly in comparison with those of the control group and the holder group. 3. In the SP9-EA group, the density of liver tissue was maintained more similarly to the normal group in comparison with those of the control group and the holder group. 5. The results of the SP9-NR group showed similar tendencies with those of the SP9-EA group, but the effects were lower than those of the SP9-EA group. Conclusion : These results suggest that electroacupuncture at SP9 has an anti oxidative effect through suppressing both the reduction of anti-oxidative enzymes and production of oxidized substances.