• Biomolecules & Therapeutics
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• 제26권2호
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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.

• 동의생리병리학회지
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• 제27권2호
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• pp.189-195
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• 2013

This study was designed to analyze the effects of methanol extracts and solvent fractions of the young branch of Prunus persica on scavenging activity of ROS, RNS and inhibiting activity of oxidative modification in human LDL induced by copper ion or free radical generator. The scavenging capacities of the fractions on DPPH radical, superoxide radical, nitric oxide and peroxynitrite were exhibited the highest in ethylacetate fraction, followed by butanol fraction. In the copper-induced LDL oxidative modification system, the highest antioxidant activity was revealed in ethylacetate fraction, and butanol fraction exhibited a similar activity. However, solvent fractions of the young branch of Prunus persica showed a relatively low antioxidant activity in the AAPH-mediated LDL oxidation. In addition, ethylacetate and butanol fractions also inhibited the copper-mediated LDL oxidation in the REM assay, which was comparable to that of the positive controls, including EDTA, ascorbic acid and BHT. Futhermore, a content of total phenolics in these two fractions was higher than that of the other fractions. These results indicated that ethylacetate and butanol fractions of the young branch of Prunus persica were useful for the prevention of the free radical- or metal ion-induced oxidative damages.

• Animal cells and systems
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• 제15권4호
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• pp.259-267
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• 2011

This study was undertaken to produce a $F_{ab}$ fragment of a human monoclonal antibody reactive to oxidized and carbamylated low-density lipoprotein (oxLDL and cLDL) using phage display technology. An analysis of DNA sequences of this $F_{ab}$, termed plaque 15,16-46 $F_{ab}$, revealed that the rearranged $V_H$ was highly mutated. Complementarity-determining regions of the $V_H$ showed a very high R/S ratio and contained many positively charged amino acids. In direct binding and competitive ELISA, the $F_{ab}$ reacted strongly with both MDA-LDL and Cu-oxLDL forms of oxLDL, and also showed high affinity for cLDL. Immunofluorescence and immunohistochemical analyses showed that this $F_{ab}$ positively stained atherosclerotic aortic plaques in $ApoE^{-/-}$ mice as well as those in patients with atherosclerosis. The $F_{ab}$ also showed positive staining in placental decidua from patients with preeclampsia. It is suggested that the plaque 15,16-46 $F_{ab}$ against oxLDL and cLDL might possibly be applicable for developing a diagnostic reagent for both human and rodent animal research to detect and characterize atherosclerotic disease progression in atherosclerotic lesions as well as exploring the pathogenesis of atherogenic diseases such as preeclampsia.

• Nutrition Research and Practice
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• 제10권5호
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• pp.477-486
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• 2016

BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

• Journal of Community Nutrition
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• 제4권3호
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• pp.151-158
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• 2002

The purpose of this study was to investigate the correlations among the anthropometry, serum lipid levels and nutrient intake in Korean female university students. The subjects were 119 female students at a university located in Incheon. This study was conducted using a self-administered questionnaire. Anthropometric data were measured and blood lipid levels were analyzed. Nutrient intake collected from 3 day-recalls was analyzed by the Computer Aided Nutritional Analysis Program. The data were analyzed by SPSS 10.0 program. Average age, height and weight of the subjects were 20.9 years, 160.1cm and 54.3kg, respectively. Average serum TG (triglyceride), total cholesterol, HDL-C (high density lipoprotein-cholesterol) and LDL-C (low density lipoprotein-cholesterol) levels of the subjects were 69.47mg/dl, 146.85 mg/dl, 50.49mg/dl and 82.52mg/dl, respectively. Average AI (atherogenic index) of the subjects was 2.03, which was in the normal range based on risk values. Average intake of most nutrients except protein, vitamin B$_1$, vitamin C and phosphorus were lower than the Korean RDA. Especially calcium and iron intakes of the subjects were under 65% of the Korean RDA. Serum TG, total cholesterol and LDL-C levels were negatively correlated with DBP (diastolic blood pressure). HDL-C/LDL-C and HDL-C/total cholesterol were positively correlated with height. Age was positively correlated with phosphorus intake. DBP of the subjects was positively correlated with calcium and iron intakes. Serum TG level was positively correlated with total cholesterol, HDL-C, LDL-C and AI, while negatively correlated with HDL-C/total cholesterol. Total cholesterol level was positively correlated with HDL-C, LDL-C and AI, while negatively correlated with HDL-C/LDL-C, HDL-C/total cholesterol. HDL-C level was positively correlated with LDL-C, HDL-C/LDL-C and HDL-C/total cholesterol, while negatively correlated with AI. LDL-C level was negatively correlated with HDL-C/LDL-C and HDL-C/total cholesterol, while positively correlated with AI HDL-C/LDL-C ratio was positively correlated with HDL-C/total cholesterol and AI. HDL-C/total cholesterol was negatively correlated with AI. Fat intake was positively correlated with total cholesterol, HDL-C level, and vitamin B$_2$ intake was positively correlated with TG, HDL-C/LDL-C. Therefore, nutrition education is necessary for female university students to promote the lipid profile and to optimize the nutritional status. (J Community Nutrition 4(3) : 151∼158, 2002)

• Nutrition Research and Practice
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• 제16권6호
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• pp.716-728
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• 2022

BACKGROUND/OBJECTIVES: An imbalanced adipokine profile in obesity increases the susceptibility to obesity-related cardiometabolic alterations, including type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease. The mulberry plant has been reported to have health benefits, such as hypolipidemic and hepatoprotective effects. This study examined the effects of a mulberry (Morus alba L.) fruit ethanol extract (MBEE) on dyslipidemia, liver steatosis, and adipokine imbalance in response to a high-fat diet. MATERIALS/METHODS: Male Sprague-Dawley rats were assigned to one of 4 groups containing 6 rats each and fed either a control diet (CON), a high-fat diet (HFD), or a high-fat diet with MBEE of 150 mg/kg/day (LMB) or 300 mg/kg/day (HMB). The triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured spectrophotometrically. The leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were determined by an enzyme-linked immunosorbent assay. RESULTS: The plasma TG levels were similar in the 4 groups. Plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and TC/HDL-C ratio increased in the HFD group compared with the CON group, whereas those values decreased in the LMB group (P < 0.05), indicating that MBEE had a plasma lipid-lowering effect. HDL-C decreased in the HFD group, but MBEE did not affect the HDL-C level. The HFD rats significantly increased hepatic TG and cholesterol levels and plasma ALT and AST activities compared to the CON group. The hepatic TG level and ALT and AST activities were reduced markedly by the MBEE treatment. The HFD group showed a higher PAI-1 level, whereas MBEE treatment, especially in the HMB group, significantly reduced leptin level, and leptin/adiponectin and PAI-1/ adiponectin ratios. These findings suggest that MBEE altered the imbalance between the pro-and anti-inflammatory adipokines to a more anti-inflammatory state. CONCLUSIONS: MBEE could protect against abnormal lipid metabolism and hepatic steatosis induced by a high-fat diet, lowering plasma cholesterol, LDL-C and TC/HDL-C, and hepatic TG. These findings are associated with the regulating effect of MBEE on the leptin/adiponectin and PAI-1/adiponectin ratios.

• BMB Reports
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• 제35권2호
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• pp.172-177
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• 2002

We previously reported that cholesteryl ester transfer protein (CETP) inhibitory peptides (designated $P_{28}$ and $P_{10})$ have anti-atherogenic effects in hypercholesterolemic rabbits (Biochim. Biophys. Acta (1998) 1391, 133-144). To further investigate those effects, we studied rabbit plasma that was collected after 30 h of a $P_{28}$ or $P_{10}$ injection. We found that there is a strong correlation between the in vivo CETP inhibition effects and alterations of lipoprotein particle size distribution in rabbit plasma, as determined on an agarose gel electrophoresis and gel filtration column chromatography. In vivo effects of the peptide were observed again in C57BL/6 mice that expressed simian CETP. The $P_{28}$ or $P_{10}$ peptide ($7\;{\mu}g/g$ of body weight) that was dissolved in saline was injected subcutaneously into the mice. The $P_{28}$ injection caused the partial inhibition of plasma CETP activity up to 50%, decreasing the total plasma cholesterol concentration by 30%, and increasing the ratio of HD/total-cholesterol concentration by 150% in the CETP-transgenic (tg) mice. The CETP inhibition by the $P_{28}$ or $P_{10}$ made alterations that modulated the size re-distribution of the lipoproteins in the blood stream. Particle size of the very low (VLDL) and low density lipoproteins (LDL) from the peptide-injected group was highly decreased compared to the saline-injected group (determined on the gel filtration column chromatography). In contrast, The HDL particle size of the $P_{28}$-injected group increased compared to the control group (saline-injected). The expression level of the CETP mRNA of the $P_{28}$-injected CETP-tg mouse appeared lower than the saline-injected CETP-tg mouse. These results suggest that the injection of the CETP inhibitory peptide could affect the CETP expression level in the liver by influencing lipoprotein metabolism.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1238-1254
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• 2023

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m² or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers.

• 생명과학회지
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• 제28권2호
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• pp.187-194
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• 2018

표고버섯으로부터 유래한 eritadenine (EA)은 혈중 low density lipoprotein (LDL), triglyceride (TG), phospholipid를 감소시키는 물질이다. 최근 저희 연구팀은 in vitro 연구에서 EA가 angiotensin converting enzyme (ACE)의 활성을 저해함을 밝혔다. 본 연구에서는 EA와 EA 함유한 표고버섯균사체 고체배양 효소추출물(EA-LEMCEE)이 본태성 고혈압 쥐 SHR의 혈압을 낮추었음을 보고한다. EA 및 EA-LEMSCEE는 인체 탯줄 혈관내피세포 EA.hy926 세포의 ACE 활성을 억제하였다. EA-LEMSCEE는 SHR의 수축기 및 이완기 혈압을 Control 처리구에 비해 유의성 있게 낮추어 처리 5주에는 Positive control인 captopril (CP) 처리와 비슷한 혈압감소 효과를 나타내었다. EA-LEMCE는 LEMSCEE에 비해 수축기 및 이완기 혈압을 감소시켰지만 유의성은 없었다. EA- LEMSCEE는 renin과 ACE 활성을 Control 처리에 비해 유의성 있게 억제하였고, angiotensin II (Ang II) 함량을 감소시켜, 처리 5주 후에 이러한 CP의 효과와 유사하였다. 또한 EA-LEMCEE는 LEMCEE에 비해 유의성 있게 renin 및 ACE 활성을 억제하였고 및 Ang II 함량을 감소시켰다. 이와 같은 결과는 EA 및 EA-LEMCEE는 본태성 고혈압 SHR의 renin과 ACE 활성을 억제하여 혈압을 낮추었고, EA 및 EA-LEMSCEE는 인체 고혈압을 낮출 수 있음을 의미한다.

• Nutrition Research and Practice
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• 제5권5호
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• pp.435-442
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• 2011

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of ${\alpha}$-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. S1 tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ${\geq}$ 150 mg/dl, or LDL ${\geq}$ 120 mg/dl, or HDL <40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.