• Preventive Nutrition and Food Science
• /
• v.1 no.1
• /
• pp.134-142
• /
• 1996

Diabetes carries an increased risk of atherosclerotic disease that is not fully explained by known car-diovascular risk factors. There is accumulating evidence that advanced glycation of structural proteins, and oxidation and glycation of circulating lipoproteins, are implicated in the pathogenesis of diabetic ather-osclerosis. Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the ather-ogenic potential of certain plasma constituents, including low density lipoptotein(LDL). Glycation of LDL is significant increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls ; enhanced uptake of LDL by the macrophages, thus stimulating foam cell formation ; increased platelet aggregation; formation of LDL-immune complexes ; and generation of oxygen free radicals, resulting on oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterzied by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation" occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age : in diabetes, their rate of accumulate is accelerated. Inhibition of glycation, oxidation and glycoxidation may form the basis of future antiaterogenic strategies in both diabetic and nondiabetic individuals.dividuals.

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

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

• Molecules and Cells
• /
• v.42 no.11
• /
• pp.747-754
• /
• 2019

The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among $CD4^+$ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

• Asian-Australasian Journal of Animal Sciences
• /
• v.24 no.12
• /
• pp.1681-1689
• /
• 2011

The beneficial effects of tea catechins (TCs) are related not only to their antioxidant potential but also to the improvement of animal meat quality. In this study, we assessed the effects of dietary TC supplementation on plasma biochemical parameters, hormone responses, and glutathione redox status in goats. Forty Liuyang goats were randomly divided into four equal groups (10 animals/group) that were assigned to four experimental diets with TC supplementation at 4 levels (0, 2,000, 3,000 or 4,000 mg TC/kg DM feed). After a 60-day feeding trial, all goats were slaughtered and sampled. Dietary TC treatment had no significant effect on blood biochemical parameters, however, low-density lipoprotein cholesterol (p<0.001), triglyceride (p<0.01), plasma urea nitrogen (p<0.01), and glucose (p<0.001) decreased and total protein (p<0.01) and albumin (p<0.05) increased with the feeding time extension, and day 20 was the turning point for most of changes. Interactions were found in glutathione (p<0.001) and the ratio of reduced and oxidized glutathione (p<0.05) in whole blood between treatment and feeding time. Oxidized glutathione in blood was reduced (p<0.05) by 2,000 mg TC/kg feed supplementation, and a similar result was observed in longissimus dorsi muscle. Though plasma glutathione peroxidase (p<0.01) and glutathione reductase (p<0.05) activities were affected by treatment and feeding time interactions, and glutathione S-transferases activity increased with feeding day extension, no changed values appeared in longissimus dorsi muscle. In conclusion, dietary TC supplementation affected the concentrations of some blood metabolites and accelerated GSH depletion in the blood of goats. In terms of less high-density lipoprotein cholesterol, the highest insulin and IGF-I concentrations, the highest ratio of reduced and oxidized glutathione in plasma, the dosage of 2,000 mg TC/kg feed might be desirable for growing goats to prevent glutathione depletion and keep normal physiological metabolism.

• Journal of Applied Biological Chemistry
• /
• v.61 no.1
• /
• pp.1-8
• /
• 2018

The objective of this study was to compare the antihyperlipidemic effects of different Dendropanax morbifera leaf extracts in vitro. The extracts differed in terms of specimen age, harvesting season, and extraction method. RAW 264.7 cells were pretreated with these extracts and stimulated by oxidized low-density lipoprotein. Ethanol was used to induce toxicity in HepG2 cells. Cellular lipid accumulation was quantified using oil red O staining in both these cells. The extracts were evaluated for their inhibitory effects on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. RAW 264.7 cells treated with the 60% ethanol extract of an 8-year-old specimen harvested in November exhibited the lowest lipid accumulation. The 30% ethanol extract of a 5-year-old specimen harvested in May exhibited the greatest protection from ethanol-induced cytotoxicity in HepG2 cells. The hot water extract of an 8-year-old specimen harvested in May showed the greatest inhibition of HMG-CoA reductase. These results showed that D. morbifera extracts prepared from leaves that are harvested in May possess the highest antihyperlipidemic effects.

• IMMUNE NETWORK
• /
• v.24 no.3
• /
• pp.15.1-15.18
• /
• 2024

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

• Animal cells and systems
• /
• v.15 no.4
• /
• pp.259-267
• /
• 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.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.27 no.2
• /
• pp.189-195
• /
• 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.

• Proceedings of the Korean Vacuum Society Conference
• /
• 2016.02a
• /
• pp.372.1-372.1
• /
• 2016

Recently, there are a lot of diseases all around the world. Out of them, Atherosclerosis (AS) is the most common cause of stroke, cardiovascular mortality, and myocardial infarction. The macrophage-derived foam cell, which is formed by oxidized low-density lipoprotein (oxLDL), is the crucial marker for AS. In this study, we report a label-free capacitance imaging technique with multi-electrode array (MEA). The lipid-rich aorta arch lesions, which are derived from an apolipoprotein-E receptor-deficient (apoE-/-) mouse, exhibit higher capacitance than the lipid-free aorta arch, allowing the capacitance imaging of lipid region in atherosclerosis. To improve the contacts between MEA and tissue, polypyrrole(PPy)-coated multi walled carbon nanotubes (MWNTs) multi electrode array (PPy-MWNTs-MEA) was fabricated. Compared to TiN-MEA, PPy-MWNTs-MEA yielded lower contact impedance and better capacitance images. In addition, we have also developed a flexible MEA using single walled carbon nanotubes on a PET substrate. The lipid region could be discriminated in the capacitance images of the lipid-rich aorta arch lesions measured using flexible MEA, demonstrating a feasibility of in vivo applications.