• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.162-168
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• 2007

It is well known that oxidized low-density lipoprotein (oxLDL) is the most characterized humoral factor that plays an important role in the pathogenesis of atherosclerosis. The water extract of the Korean herbal remedy, ZoaGumHwan (ZGH), which is composed of roots of Coptis chinensis Franch and fruits of Evodia officinalis Dode with the ratio of 6 to 1, reduced the in vitro oxidation of low density lipoproteins (LDL). Also, the ZGH extract and berberine, one of the major components of ZGH, significantly prevented oxLDL-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). Furthermore, the ZGH water extract and berberine decreased oxLDL-induced expression of CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor, in U937 human monocytic cells. The protective effects of the ZGH water extract and berberine were similar to those of simvastatin, an effective lipid-lowering drug. The results suggest that Korean herbal remedy, ZGH, seems to have protective effect against oxLDL-induced monocyte chemoattractant protein (MCP)-1/CCR2-dependent monocyte recruitment onto endothelial cells.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.800-807
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• 2001

This study was designed to investigate the antioxidative activity of a substance isolated from. The antioxidative activity of procyanidine was higher than that of dl-tocopherol and BHA on low-density lipoprotein (LDL) oxidation by thiobarbituric acid reactive substance (TBARS). Procyanidine inhibited the copper-mediated oxidation of human LDL in a dose dependent manner with almost complete inhibition at $60{\mu}g/mL$. Procyanidine at a concentration of $80{\mu}g/mL$ in hibited oxidation of LDL induced by J774. LDL oxidized by copper-mediated or cell-induced oxidation was degraded at a much greater rate than native LDL. These results suggested the importance of further research to procyanidine in the investigation of atherosclerosis and free radical-induced injury.

• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.85-91
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• 2016

Objectives: This study investigated the effects of Scutellariae Radix extract (SRE) on lipids metabolism, oxidation and the production of pro-inflammatory cytokines in rats fed highly oxidized fat. Methods: To induce obesity, male Sprague‐Dawley rats were fed a highly oxidized fat diet for 10 weeks. SRE at 100 mg/kg were administered orally to obesity-induced rats for 6 weeks, and their lipid metabolism, oxidation and production of pro-inflammatory cytokines were examined. Results: The concentrations of free fatty acid, triglyceride, total cholesterol, and low density lipoprotein-cholesterol in plasma decreased in SRE-treated groups, although the difference was not significant between control and SRE-treated groups, while that of high density lipoprotein-cholesterol significantly increased in SRE group. The concentrations of total cholesterol and triglyceride in the liver were tended to decrease in SRE-treated group. The concentrations of thiobarbituric acid in plasma and liver were lower in SRE group than in control group. The levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in plasma were decreased in SRE group. Activities of glutathione peroxidase, superoxide dismutase, and catalase in liver were tended to increase in the SRE group. The plasma concentrations of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$ and IL-6 were lower in SRE group than in control group, while that of IL-10 was higher. The liver concentrations of $IL-1{\beta}$, $TNF-{\alpha}$, and IL-6 were tended to decrease while that of IL-10 tended to increase in SRE group. Conclusions: Finally SRE could be used in the production of nutraceuticals for lowering lipids and exerting anti-oxidation and anti-inflammatory effects in obesity rats fed highly oxidized rat.

• Journal of Microbiology and Biotechnology
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• v.32 no.11
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• pp.1406-1415
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• 2022

The formation of macrophage foam cells stimulated by oxidized low-density lipoprotein (ox-LDL) is deemed an important cause of atherosclerosis. Transcription factor Yin Yang 1 (YY1), which is a universally expressed multifunctional protein, is closely related to cell metabolism disorders such as lipid metabolism, sugar metabolism, and bile acid metabolism. However, whether YY1 is involved in macrophage inflammation and lipid accumulation still remains unknown. After mouse macrophage cell line RAW264.7 cells were induced by ox-LDL, YY1 and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions were found to be increased while low-density lipoprotein receptor (LDLR) expression was lowly expressed. Subsequently, through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, Oil Red O staining and cholesterol quantification, it turned out that silencing of YY1 attenuated the inflammatory response and lipid accumulation in RAW264.7 cells caused by ox-LDL. Moreover, results from the JASPAR database, chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and Western blot analysis suggested that YY1 activated PCSK9 by binding to PCSK9 promoter and modulated the expression of LDLR in the downstream of PCSK9. In addition, the results of functional experiments demonstrated that the inhibitory effects of YY1 interference on ox-LDL-mediated macrophage inflammation and lipid accumulation were reversed by PCSK9 overexpression. To sum up, YY1 depletion inhibited its activation of PCSK9, thereby reducing cellular inflammatory response, cholesterol homeostasis imbalance, and lipid accumulation caused by ox-LDL.

• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.965-974
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• 2017

The single-chain variable fragment (scFv) against lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a promising molecule for its potential use in the diagnosis and immunotherapy of atherosclerosis. Producing this scFv in several milligram amounts could be the starting point for further engineering and application of the scFv. In this study, the abundant expression of the anti-LOX-1 scFv was attempted using Escherichia coli (E. coli) and Brevibacillus choshinensis (B. choshinensis). The scFv had limited soluble yield in E. coli, but it was efficiently secreted by B. choshinensis. The optimized fermentation was determined using the Plackett-Burman screening design and response surface methodology, under which the yield reached up to 1.5 g/l in a 5-L fermentor. Moreover, the properties of the scFvs obtained from the two expression systems were different. The antigen affinity, transition temperature, and particle diameter size were 1.01E-07 M, $55.2{\pm}0.3^{\circ}C$, and 9.388 nm for the scFv expressed by B. choshinensis, and 4.53E-07 M, $52.5{\pm}0.3^{\circ}C$, and 13.54 nm for the scFv expressed by E. coli. This study established an efficient scale-up production methodology for the anti-LOX-1 scFv, which will boost its use in LOX-1-based therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.93-99
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• 2002

Effects of oxidized low-density lipoprotein (ox-LDL), $1-{\alpha}-stearoyl-lysophosphatidylcholine$ (LPC), on intracellular $Ca^{2+}$ concentration were examined in mouse endothelial cells by measuring intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ with fura 2-AM and reverse transcription-polymerase chain reaction (RT-PCR). LPC increased $[Ca^{2+}]_i$ under the condition of 1.5 mM $[Ca^{2+}]_o$ but did not show any effect under the nominally $Ca^{2+}-free$ condition. Even after the store depletion with $30{\mu}M$ 2,5-di-tert- butylhydroquinone (BHQ) or $30{\mu}M$ ATP, LPC could still increase the $[Ca^{2+}]_i$ under the condition of 1.5 mM $[Ca^{2+}]_o.$ The time required to increase [$Ca{2+}$]i (about 1 minute) was longer than that for ATP-induced $[Ca^{2+}]_i$ increase $(10{\sim}30\;seconds).$ LPC-induced $[Ca^{2+}]_i$ increase was completely blocked by $1{\mu}M\;La^{3+}.$ Transient receptor potential channel(trpc) 4 mRNA was detected with RT-PCR. From these results, we suggest that LPC increased $[Ca^{2+}]_i$ via the increase of $Ca^{2+}$ influx through the $Ca^{2+}$ routes which exist in the plasma membrane.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.2
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• pp.108-117
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• 2006

The oxidative notification of low density lipoprotein(LDL) has been implicated in the development of atherosclerosis. Oxidized LDL are found in macrophage foam cell, and it can induce an macrophage proliferation in atherosclerotic plaque. In this study, we investigated the hypothesis that Samkieum may reduce atherosclerosis by lowering the oxidiazability of LDL, To achieve this goal, we examined the effect of Samkieum on LDL oxidation nitric oxide production in mouse macrophage cell line, RAW264.7, and the effect of Samkieum on cupuric sulfate-induced cytotoxicity, LDH release, and macrophage activity. Samkieum inhibited the generation 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, Samkieum activated RAW264.7 cell, and prolonged the survival time, and increased nitric oxide production in Raw 264.7 cells.

• Journal of Society of Preventive Korean Medicine
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• v.5 no.1
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• pp.134-143
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• 2001

The oxidative modification of low density lipoprotein(LDL) has been implicated in the development of atherosclerosis. Oxidized LDL are found in macrophage foam cell, and it can induce an macrophage proliferation in atherosclerotic plaque. In this study, we investigated the hypothesis that gamisoyosan(GS) may reduce atherosclerosis by lowering the oxidiazability of LDL, To achive this goal, we examined the effect of GS on LDL oxidation, nitric oxide production in mouse macrophage cell line, RAW264.7, and the effect of GS on cupuric sulfate-induced cytotoxicity, LDH release, and macrophage activity. GS inhibited the generation 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, GS activated RAW264.7 cell, and prolonged the survival time, and increased nitric oxide production in Raw 264.7 cells.

• Molecules and Cells
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• v.38 no.12
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• pp.1096-1104
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• 2015

Particulate $matter_{2.5}$ ($PM_{2.5}$) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which $PM_{2.5}$ aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous $PM_{2.5}$ solution on lipoprotein metabolism. Collected $PM_{2.5}$ from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. $PM_{2.5}$ extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. $PM_{2.5}$ treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by $PM_{2.5}$ solution in a dose-dependent manner. Further, $PM_{2.5}$ solution caused cellular senescence in human dermal fibroblast cells. Microinjection of $PM_{2.5}$ solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of $PM_{2.5}$ induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.