• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.510-517
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• 2016

This study was conducted to investigate the antioxidant and hepatoprotective effects of eriodictyol compound against hydrogen peroxide-induced oxidative stress in HepG2 cells by measuring expression levels of antioxidant enzymes, liver function index enzyme activities, and inhibitory effects against reactive oxygen species (ROS) production. HepG2 cell viability was assessed using 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the concentration range of $10{\sim}50{\mu}g/mL$, eriodictyol displayed over 98% cell viability in HepG2 cells. The effects of increased gene expression on hydrogen peroxide-induced oxidative stress were analyzed by monitoring antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx) gene expression levels using real-time PCR. Eriodictyol compound significantly increased gene expression levels of SOD, CAT, and GPx in a dose-dependent manner ($10{\sim}50{\mu}g/mL$). Hepatoprotective effects against hydrogen peroxide-induced oxidative stress were analyzed by monitoring glutamic oxaloacetic transaminase (GOT), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) activities in HepG2 cell culture medium using a biochemistry analyzer. Eriodictyol compound significantly reduced GOT, LDH, and GGT activities in a dose-dependent manner in HepG2 cells. ROS level in HepG2 cells was analyzed by 2',7'-dichlorofluorescein fluorescence diacetate assay, and eriodictyol compound effectively reduced the intracellular ROS level in HepG2 cells. The results reveal that eriodictyol compound can be useful for development of effective antioxidant and hepatoprotective agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.1
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• pp.17-25
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• 2013

This study was performed to investigate the effects of the hot water extract of red garlic (RG) and RG-composites on fecal lipid levels and hepatic antioxidant enzyme activity in rats fed a high fat-cholesterol diet. Three different types of RG-composites prepared: RG and green tea (RGT), RG and dietary fiber (RGF), and RG, green tea, and dietary fiber (RGTF). Rats were divided into six groups: the control, the group fed a high fat-cholesterol diet (HFC), the RG-supplemented group (HRG), the RGT supplemented group (HRGT), the RGF supplemented group (HRGF), and the RGTF supplemented with HFC group (HRGTF). The antioxidant activity of these composites was tested, in vitro. The DPPH radical scavenging activity was higher RGT and RGTF than RG. ABTs radical scavenging activity of RGT was similar to RGTF. Their activities were significantly higher than RG. The reducing power was similar to their radical scavenging activities. Total lipid levels in the liver and triglyceride levels in the heart were lower in the groups fed RG-composites than the HRG group. Fecal total lipid level was higher in the HRGF and HRGTF groups than the HRG group after 4 weeks diet supplementation during 4 weeks. Lipid peroxide content was reduced to anywhere between 6.2% and 12.1% in the groups fed RG-composites, compared to the HFC group. Antioxidant activity was significantly higher in the groups fed RG-composites than the HFC group. Hepatic SOD activity was higher in the groups fed RG-composites than the HRG group. The HRGT group in catalase activity, and the HRGT and HRGTF groups in GSH-px activity were increased significantly compared to the HFC group. Hepatic UDPGT activity was increased significantly in the HRGT and HRGTF groups to the HFC group, as well. These results indicate that antioxidant activities of the RG-composites were related to the decrease of lipid levels by increasing the fecal excretion and enhancement of hepatic antioxidant enzyme activity in rats fed a high fat-cholesterol diet.

• Korean Journal of Medicinal Crop Science
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• v.8 no.3
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• pp.225-233
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• 2000

There was not noticeable differences in decreasing blood alcohol concentrations between Korea and China-produced Hovenia dulcis $T_{HUNB}$, showing only 1-2 % higher decreasing rate for Korea-produced seed extracts than those from China. It was also found that the blood alcohol decreasing ability was greatly enhanced by partitioning the crude extracts produced from both places. The both extracts (crude and partitioned) accelerated the reducing rate of blood alcohol concentrations down to 1-2 hours, compared to that of control (taking only ethanol). The crude extracts from imported seeds seemed to have slightly better effect on improving in vivo ADH and ALDH activities than domestic ones; however, not for partitioned extracts. It was interesting that the partitioned extracts from both countries enhanced ADH enzyme activity up to 60% than the crude, compared to the control, while ALDH activity was not much affected by the partitioned extracts. It was also confirmed that both ADH and ALDH activities were well balanced in controlling blood alcohol concentration maintaining 28-29% of enzyme activities in vivo. The extracts proved to have better effect on enhancing ALDH activity than ADH activity, which is one of possible explanation that Hovenia dulcis $T_{HUNB}$ can effectively relieve the hangover by fast decreasing acetaldehyde concentration in the liver and blood. GST activity was also increased in the range of 120 to 300% by adding crude or partitioned extracts from both countries; however, there was no difference in enhancing GST activity between the extracts from two countries. The extracts showed competitive inhibition with GST activity, showing the reduction of enzyme activity at higher than 0. 6 (g/L) of the imported extracts.

• Journal of Nutrition and Health
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• v.35 no.4
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• pp.414-420
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• 2002

The effects of Cordyceps militaris on weight gain, flood intakes, flood efficiency ratios, serum and hepatic lipid concentrations, serum protein levels and serum enzyme activities, were studied in adult male rats. Sprague-Dawley rats, 35 weeks old, were given four different types of diets for a succeeding period of five weeks: either a normal diet(5% com oil), a high fat diet(5% com oil + 15% lard). a CF diet (high fat diet + 3% Suiting body of cordyceps militaris), or a CM diet (high fat diet + 3% mycelium of cordyceps military). The body weight gains, hepatic weights and food efficiency ratios of the rats find (high fat) diets with CF and CM were significantly decreased compared with those find the high fat diet, but were similar to those find the normal diet. The concentrations of serum and hepatic triglycerides, and hepatic total lipids and cholesterol, of rats given CF or CM diets were significantly lower than those given the high fat diet. But the concentrations of total cholesterol, HDL-cholesterol, phopholipid and total protein in the serum of rats find the high fat, CF or CM diets were significantly higher than those find the normal diet. In the serum of the rats find the CF diet, the HDL-cholesterol/total cholesterol ratio was significantly higher but the atherogenic index was significantly lower than those fed the high fat diet. The alkaline phosphatase activity in the serum of the rats find the high fat, CF, and CM diets was more significantly decreased compared to rats on the normal dirt. No differences were noted in the weights of the pancreas, kidney and heart, the serum concentrations of glucose, hemoglobin and albumin, and the activities of GOT, GPT and ${\gamma}$-GTP, among the rats on all the experimental diets. In conclusion, the rats find the Cf or CM diets maintained normal body and hepatic weights. Despite of the high intake of fats in the CF and CM diets, the concentrations of total lipids, cholesterol and triglycerides were decreased in the liver, also, the concentration of triglycerides was decreased in the serum.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.6
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• pp.987-995
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• 2009

The effects of Kwamaegi on serum lipid profiles and ROS(reactive oxygen spices) generating and scavenging enzyme activities were investigated in rats. The three experimental groups were divided as follows: normal control diet group (NC), 5% naturally prepared and freeze-dried Kwamaegi supplemented diet group (NPK) and 5% chitosan-ascorbate treated and artificially dried (CWDD: Chilly Wind & Dehumidification Drier) Kwamaegi supplemented diets group (CAK). There were no significant differences in weight gain, feed intake, feed efficiency ratio or organs weights per body weight including liver, kidney, heart and spleen among the group. In addition, there were no significant differences in serum triglyceride and total cholesterol contents. The HDL-cholesterol contents of the NC, CAK and NPK groups were 62.00, 36.48 and 78.44 mg/dL while LDL-cholesterol contents were 62.00, 36.48 and 78.44 mg/dL, respectively, which were significantly different. The atherogenic indeces in the experimental groups were 0.62, 1.20 and 0.13, respectively. There were no significant differences in total XOD (xanthine oxidoreductase) activities; however XOD type O activity was higher in the NPK group than un the NC group and in the CAK group XOD type O activity was 21~45% lower compared to NC and NPK groups. SOD (superoxide dismutase) activity was significantly higher in the CAK group than in the NC and NPK groups, while there were no significantly differences in GST (glutathione S-transferrase) activity among the groups. Furthermore, serum ALT activity was higher in the NPK group versus the NC and CAK groups. GSH (glutathione) content was higher and LPO (lipid peroxide) content lower in the CAK group compared to the NC and NPK groups. Forem the above results, we suggest that CA treated and artificially dried Kwamaegi is not only a hygienic product but also has lowering effects on LDL-cholesterol and the atherogenic index together with the lowering of ROS-generating and increasing of ROS-scavenging enzyme activities compared to other natural products.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.8
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• pp.1310-1317
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• 2003

Effects of dietary cholesterol and/or taurine supplementation on plasma and hepatic lipid peroxidation status and antioxidant enzyme activities were evaluated in rats fed one of the following semisynthetic diets for 5 weeks: control diet (CD, cholesterol-free and taurine-free diet); high cholesterol diet (HCD, CD+1.5% cholesterol): high taurine diet (HTD, CD+1.5% taurine): high cholesterol and high taurine diet (HCHTD, HCD + 1.5% taurine). Plasma malondialdehyde (MDA) level was not influenced by dietary cholesterol or taurine supplementation, while hepatic MDA level was 70% higher in rats fed HCD compared to the value for CD rats (p<0.05). Our observation that taurine supplementation significantly decreased the hepatic MDA level of rats fed HCD, but failed to decrease lipid peroxidation of rats fed CD indicates that the protective effect of taurine in the liver against lipid peroxidation is manifested only under the hypercholesterolemic environment. Plasma and hepatic glutathione peroxidase (GSH-Px) activities were not affected by dietary supplementation of cholesterol or taurine. However, hepatic superoxide dismutase (SOD) activity was significantly reduced by dietary taurine supplementation (p <0.05), and thus significantly lower in rats fed HTD compared to the value for CD (p<0.05). Plasma total cholesterol concentration was positively correlated with hepatic cholesterol concentration as expected (r=0.712, p<0.001). Plasma (r=0.399, p<0.05) and hepatic cholesterol levels (r=0.429, p<0.05) showed a significantly positive correlation with hepatic MDA concentration, respectively. Plasma taurine concentration was negatively correlated with hepatic SOD activity (r=-0.481, p<0.01), and tended to be negatively correlated with hepatic GSH-Px activity without showing statistical significance (r=-0.188, p<0.05). These results indicate an antioxidative effect of taurine in rats with elevated level of lipid Peroxidation due to high intake of dietary cholesterol. Future application of taurine as a safe candidate for a hypolipidemic agent without adversely affecting body's antioxidant defense system is speculated.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.72-79
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• 2007

Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.78-86
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• 2018

Purpose: We aimed to delineate clinical spectrum and short-term effects after enzyme replacement therapy (ERT) for 5 mucopolysaccharidosis type II (MPS II). Methods: Five patients were diagnosed with MPS II by clinical findings, enzyme activity, and genetic testing. Idursulfase was administered by intravenous infusion at a dose of 0.5 mg/kg every week. Observational chart analysis of patients, who underwent systematic investigations more than 12 months after initiation of ERT was done retrospectively. Results: Three patients were classified as having the attenuated type, and 2 patients were classified as having the severe type. The median age at the diagnosis was 9.6 years (range 3.4-26 years). Four different mutations in 5 Korean patients (4 families) with MPS II were identified, among which two were novel mutations (1 small insertion mutation: p.Thr409Hisfs*22, and 1 missense mutation: p.Gly134Glu). Two severe type sibling patients with the same mutation had different clinical manifestation. Urinary glycosaminoglycan excretion decreased within the twelve months of ERT (P=0.043). Liver and spleen volumes showed reductions that were maintained in all patients (P=0.043 and P=0.043, respectively). Improvements were also noted in left ventricular mass index (P=0.042), shoulder flexion (P=0.043), shoulder abduction (P=0.039), knee flexion (P=0.043), elbow flexion (P=0.042), and respiratory distress index (P=0.041). Conclusion: This study demonstrates that Korean patients with MPS II are clinically heterogeneous and indicates that idursulfase is relatively effective in several clinical parameters including heart size and respiratory distress index without infusion-related reactions in patients with MPS II.

• Journal of Life Science
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• v.34 no.2
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• pp.113-121
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• 2024

Endoplasmic reticulum (ER) stress responses are markedly induced during toxic responses caused by various chemical substances, including difenoconazole, but no research has been conducted on 1,2,3-trichloropropane (TCP), a chemical that is generally used in agriculture and industry, which induces hepatotoxicity. Therefore, in this study, the changes in indicators for hepatotoxicity, apoptosis, and ER stress were analyzed in TCP-treated Sprague Dawley (SD) rats to study the regulatory mechanism of ER stress during the hepatotoxicity. The TCP-treated group decreased in body weight and dietary intake compared to the vehicle-treated group, and necrosis and vacuolation increased significantly in liver histology. In addition, the expression of apoptosis-related factors, including Bax/Bcl-2 and cleaved caspase (Cas)-3/Cas-3 increased significantly in the TCP-treated group compared to the vehicle-treated group. In the analysis of ER stress response indicators, the expression of C/EBP homologous protein (CHOP), phospho-eukaryotic translation initiation factor 2 alpha subunit (eIF2α), and phospho-inositol-requiring enzyme 1α (IRE1α) increased only in the TCP100-treated group and decreased in the TCP200-treated group. However, the transcriptions of growth arrest and DNA damage-34 (GADD34) increased in the TCP200-treated group, while Spliced X-box binding protein-1 (XBP1s) and unspliced XBP1(XBP1u) decreased in the same group. These results suggest that the ER stress response is successfully triggered during the hepatotoxicity induced by TCP treatment through the alternative regulation of the unfolded-protein response (UPR) pathway.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.16-22
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• 2004

Background: To develop a novel treatment strategy for hepatitis B virus infection, a major cause of liver chirosis and cancer, we aimed to make human monoclonal antibodies inhibiting RNase H activity of P protein playing in important role in HBV replication. In this regard, phage display technology was employed and demonstrated as an efficient cloning method for human monoclonal antibody. So this study analysed the usability of human monoclonal antibody as protein based gene therapy. Methods: RNase H of HBV was expressed as fusion protein with maltose binding protein and purified with amylose resin column. Single chain Fv (scFv) phage antibody library was constructed by PCR cloning using total RNAs of PBMC from 50 healthy volunteers. Binders to RNase H were selected with BIAcore 2000 from the constructed library, and purified as soluble antibody fragment. The affinity and sequences of selected antibody fragments were analyzed with BIAcore and ABI automatic sequencer, respectively. And finally RNase H activity inhibiting assay was carried out. Results: Recombinant RNase H expressed in E. coli exhibited an proper enzyme activity. Naive library of $4.46{\times}10^9cfu$ was screened by BIAcore 2000. Two clones, RN41 and RN56, showed affinity of $4.5{\times}10^{-7}M$ and $1.9{\times}10^{-7}M$, respectively. But RNase H inhibiting activity of RN41 was higher than that of RN56. Conclusion: We cloned human monoclonal antibodies inhibiting RNase H activity of P protein of HBV. These antibodies can be expected to be a good candidate for protein-based antiviral therapy by preventing a replication of HBV if they can be expressed intracellularly in HBV-infected hepatocytes.