• Journal of Haehwa Medicine
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• v.25 no.1
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• pp.133-144
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• 2016

Objectives : This study was aimed to investigate the effect of ACLL extract (Artemisia capillaris Thunb, Curcuma longa L, Lycium chinense, Ligustrum lucidum Aiton complex extract) in a dyslipidemia animal model induced by a high-fat diet. Methods : ACLL extracts was administered at 200 mg/kg, and 400 mg/kg to Apoe mice, where arthritis was induced by high cholesterol diet. After mice were treated with GO for 4 weeks, we measured AST, ALT, BUN and lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride), atherogenic index(AI) and cardiac risk factor(CRF). Results : Serum AST, ALT, creatinine, BUN levels were not changed by ACLL extract do not show any toxic effects. Also, ACLL extract groups were found to have atherogenic Index and cardiac risk factor as well as lipid metabolism improvement (total cholesterol, LDL cholesterol and triglyceride decrease). Conclusions : We suggest that ACLL extract may have the control effects of Dyslipidemia by improving lipid metabolism.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.463-471
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• 1999

Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

• Molecules and Cells
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• v.45 no.8
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• pp.575-587
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• 2022

Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 Å resolution, respectively. Metal-free porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency.

• Herbal Formula Science
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• v.26 no.3
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• pp.237-250
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• 2018

Objectives : This study is a pharmacological network approach, aimed to identify the potential active compounds contained in Curcumae Radix, and their associated targets, to predict the various bio-reactions involved, and finally to establish the cornerstone for the deep-depth study of the representative mechanisms. Methods : The active compounds of Curcumae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : The target information from 32 potential active compounds of Curcumae Radix was collected through TCMSP analysis. The active compounds interact with 133 target genes engaging in total of 885 biological pathways. The most relevant pathway was the lipid-related metabolism, in which 3 representative active compounds were naringenin, oleic acid, and ${\beta}-sitosterol$. The mostly targeted proteins in the lipid pathway were ApoB, AKT1 and PPAR. Conclusions : The pharmacological network analysis is convenient approach to predict the overall metabolic mechanisms in medicinal herb research, which can reduce the processes of various experimental trial and error and provide key clues that can be used to validate and experimentally verify the core compounds.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.3
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• pp.530-539
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• 1994

All lipoproteins are made up of three major classes of lipids : triglycerides, cholesterol, and phospholipids. Lipoproteins vary in their relative content of these lipids as well as in size and protein content. Human low density lipoprotein (LDL) is a main carrier for cholesterol in the blood stream, and it is well established that cholesterol deposits in the arteries stem primarily from LDL and that increased levels of plasma LDL correlated with in increased risk of atherosclerosis. Various lines of research provide strong evidence that lDL may become oxidized in vivo and that oxidized-LDL is the species involved in the formation of early atherosclerotic lesions. the most crucial findings in this context are the following : (1) Oxidized -LDL has chemotactic properties and if present in the intimal space of the arteries would recruit blood monocytes which then can develop into tissue macrophages ; (2) marcrophages take up oxidized-LDL unregulated to from lipid laden foam cells ; (3) Oxdized-LDLis highly cytotoxic and could be responsible for damage of the endothelial layer and for the destruction of smooth muscle cells.

• Analytical Science and Technology
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• v.25 no.5
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• pp.333-338
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• 2012

IQ motif-containing GTPase-activating proteins (IQGAPs), which are well-known $Ca^{2+}$-independent calmodulin (CaM) binding proteins, are involved in various cellular functions such as cell proliferation, carcinogenesis and cell migration. The IQGAP3 similar to IQGAP1 has four repeated IQ motifs, which are crucial for CaM binding. It has been recently shown that all four IQ motifs of the IQGAP1 could bind to CaM, while not clear the binding of four IQ motifs of the IQGAP3. In this study, we examined the binding between CaM and each IQ motif of IQGAP3. As a result, we found that IQ2 and IQ3, but not IQ1 and IQ4, have a $Ca^{2+}$-independent CaM binding activity. We also found that IQ(3.5-4.4) on the IQGAP3 has $Ca^{2+}$-dependent CaM binding activity as similar with that of IQGAP1. This finding indicates that IQ motifs of the IQGAP3 plays a dynamic role via different interaction of IQ motifs with $Ca^{2+}$/CaM or apoCaM.

• Journal of Nutrition and Health
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• v.40 no.7
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• pp.630-638
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• 2007

This study was performed to examine the combined effects of L-carnitine and isoflavone supplementation on weight reduction and body fat distribution in overweight women. Overweight/obese women (body mass index > $23kg/m^2$) who were not diagnosed any type of diseases were included in this study and sixty subjects ($41.1{\pm}1.5$ years, $25.9{\pm}0.3kg/m^2)$ were randomly assigned to a placebo (n=30) or a supplement group (n=30, L-carnitine 300 mg+isoflavone 40 mg/day). We measured anthropometric parameters, abdominal fat distribution by computerizd tomography and blood components before and after the 12 week intervention period. After the 12 weeks of supplementation, subjects in L-carnitine and isoflavone supplement group showed a significant reduction of body weight (p < 0.001), body fat % (p < 0.05), and waist to hip ratio (p < 0.01) whereas placebo group did not show any changes. In a CT-scanned results, total fat area at L4 level was significantly reduced by 8.1% (p < 0.01) with the reduction of visceral fat area (-11.1%, p < 0.001) and subcutaneous fat area (-7.0%, p < 0.05) in the supplement group. The supplementation of L-carnitine and isoflavone showed the significant improvement of HDL-C (p < 0.01) and apoB (p < 0.05) concentrations, however, change values in those markers were not significant compared with those of the placebo group. In addition, a significant increase of adiponectin level (p<0.001) was observed in the supplement group after the intervention. The result of present study demonstrated that supplementation of 300 mg L-carnitine and 40 mg isoflavone per day fur 12 weeks can give beneficial effects on weight reduction and visceral fat accumulation. These potential antiobesity supplement can produce more favorable effects when combined with lifestyle modification.

• Journal of Pharmacopuncture
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• v.9 no.1
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• pp.5-20
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• 2006

Objectives : This study was carried out to identified the effects of distilled cultivated wild ginseng pharmacopuncture to the obesity. Methods : Cultivated wild ginseng pharmacopuncture was administered on the points of chung-wan(CV12), $Ch'{\breve{o}}nch'u$(ST25), and Chok-samni(ST36) on lowering lipid and oxidative capacity in biochemical and molecular biological aspects were investigated in obese rats fed with high fat diet. Results : 1. The contents of plasma ${\beta}-lipoprotein$ showed a tendency to decrease in the pharmacopuncture groups compared to the control group. In the pharmacopuncture groups, the values of ST25 and ST36 pharmacopuncture groups showed lower value. 2. The contents of plasma free fatty acids showed a tendency to decrease in pharmacopuncture groups compared to the control group. However, in the pharmacopuncture groups, the values were not significantly different. 3. Plasma triglyceride and glucose showed lower value in the ST25 pharmacopuncture groups compared with the other groups. 4. The activity of AST showed a tendency to decrease in the pharmacopuncture groups. However, the activity of ALT was not significantly different in all the treatment groups. 5. Plasma total cholesterol and LDL-cholesterol showed lower value in the ST25 and ST36 pharmacopuncture groups and HDL-cholesterol showed higher value in the CV12 pharmacopuncture groups than that of the other treatment groups. 6. Liver total cholesterol values didn't show significant difference in all the treatment groups, and triglyceride showed lower value in the pharmacopuncture groups. 7. The contents of plasma TEARS showed lower value in the ST25 pharmacopuncture group and contents of liver TBARS showed a tendency to decrease in the pharmacopuncture groups. However these values didn't show significant difference in the pharmaco puncture groups. 8. Liver super oxide dismutase activity showed higher value in the ST25 and ST36 pharmacopuncture groups, and the value of liver glutathione peroxidase and catalase activity showed a tendency to increase in the pharmacopuncture groups. However, these values showed no significant difference in the pharmacopuncture groups. 9. Expression of apo-B and E mRNA in liver cells was lower in the ST25 pharmacopuncture group than that of the other treatment groups. However, expression of $TNF-{\alpha}$ and leptin mRNA in adipose cell showed no difference among all the treatment groups. 10. ST25 pharmacopuncture group showed a good histological character of liver. It showed similar to that of normal group. However other treatment groups and control group showed slight vasodilation and slight fat accumulation. Conclusion : These results indicate that distilled cultivated wild ginseng pharmacopuncture suppressed adipose tissue mass and lipid peroxidation, and increased antioxidant capacity.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.339-344
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• 2004

Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

• Journal of Nutrition and Health
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• v.43 no.2
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• pp.123-131
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• 2010

This study was performed to examine the combined effects of gamma linolenic acid and isoflavone supplementation on menopausal symptoms and serum lipids in 73 postmenopausal women. A total subjects were randomly assigned to isoflavone (30 mg) + gamma-linolenic acid (110 mg) group or placebo group. We measured menopausal symptoms by modified Kupperman Index (KI) and oxidized LDL, lipid peroxides, blood components and anthropometric parameters before and after the 12 week intervention period. After the 12 weeks of supplementation, supplement group and placebo group showed a significant reduction of modified kupperman index (p < 0.001). Isoflavone (30 mg) + gamma-linolenic acid (110 mg) supplement group showed a significant reduction of oxidized LDL cholesterol concentration (p = 0.006) whereas placebo group did not show significant change. Isoflavone and gamma-linolenic acid consumption did not significantly affect plasma concentrations of total, LDL, HDL cholesterol, triglyceride, apo A1, B and blood components. The result of present study demonstrated the supplementation of 30 mg isoflavone and 110 mg gamma-linolenic acid per day for 12 weeks may protect LDL cholesterol from oxidative stress.