• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.153-169
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT, Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT+YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.20-27
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• 2011

Hovenia dulcis Thunb (HDT) has been known folk medicine and has been used as therapeutic drug in the treatment of liver disease. Also it has been used as a detoxifying agents for alcoholic poisoning and promoting diuresis. However, there has not been any study on therapeutic effect of Hovenia dulcis extract on $CCl_4$ induced liver and kidney damage in rats. In this study, we report on therapeutic effects of Hovenia dulcis extract on $CCl_4$ induced liver and kidney damage in rats. Rats were divided into four groups of eighteen animals. Control group (DW) was administrated with distilled water 2.5 mL/kg per peritonial administration and then $CCl_4$ group (CCl) was administrated $CCl_4$ 2.5 mL/kg per peritonial administration, $CCl_4$+HDT extract group ($CCl_4$+HDT) was administrated HDT extrat (100 mg/kg) after $CCl_4$ 2.5 mL/kg administration, $CCl_4$+Silymarin group ($CCl_4$+Sily) was administrated Silymarin (50 mg/kg) after $CCl_4$ 2.5 mL/kg administration. The complete blood cell (CBC) count of RBC, WBC, PCV, Hb, MCH, MCV, MCHC and blood chemistry profile of AST, ALT, GGT, ALP, Total choloesterol, Tryglyceride, Total bilirubin, Amylase, Glucose, BUN, Creatinine, Lipase and pathologic changes were observed for 7 days after administration of D.W., $CCl_4$, $CCl_4$+HDT extract, $CCl_4$+Silymarin. The results are as follows : 1. RBC and PCV were significantly (p < 0.01) increased in all groups compared to D.W. but hemoglobin, MCH, MCV and MCHC were not showed significant difference during experimental periods. 2. AST, ALT, T-cholesterol, T-bilirubin, TG were significantly (p < 0.05) increased in all groups on day 3 compared to D.W. and were normal on day 7. 3. ALP was significantly (p < 0.05) decreased in $CCl_4$+HDT group on day 3 but Amylase was not showed significant difference during experimental periods. 4. BUN was significantly (p < 0.05) increased in $CCl_4$ group on day 7, but $CCl_4$+HDT group and $CCl_4$+Sily group were normal. Creatninie was significantly (p < 0.05) increased in $CCl_4$ group on day 3 and normal on day 7 but $CCl_4$+HDT group and $CCl_4$+Sily group were not showed significant difference during experimental periods.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.8
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• pp.1206-1211
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• 2006

The effects of taurine supplementation on growth performance, serum and liver concentrations of lipid, fatty acid composition and lipid peroxidation in the livers of broilers under chronic heat exposure conditions were investigated. The chicks with a similar body weight were equally assigned to one of three controlled-environment chambers. The brolier chicks, which were kept at $34^{\circ}C$ were fed either with a control diet or the control diet supplemented with 0.8% taurine, whereas broiler chicks kept at $22^{\circ}C$ were fed a control diet. Both of the BW and BW gains of broilers maintained at a temperature of $34^{\circ}C$ were significantly lower than those of the control group, which was maintained at a temperature of $22^{\circ}C$ (p<0.05). However, taurine addition in the diet of birds submitted to heat stress siginficantly improved BW gain (p<0.05). The feed intake of chicks declined with increases in temperature. The relative liver and gall bladder weights of chicks fed the control diet and maintained at $34^{\circ}C$ were significantly lower than those measured in the control birds (p<0.05). However, dietary taurine was found to compensate for these reductions in liver and gall bladder weights. Relative weights of abdominal fat did not differ significantly among the three groups. Serum triglyceride concentrations were significantly lower in the chicks fed the control diet and maintained at $34^{\circ}C$ compare to those measured in the chicks fed the control diet at $22^{\circ}C$ (p<0.05). Heat stress resulted in a significant reduction in total lipid and triglyceride levels, but also increased the levels of total cholesterol in the liver (p<0.05). However, dietary taurine supplementation under the heat stress condition resulted in the recovery, to control levels, of serum triglyceride concentrations, as well as the amounts of total lipids, triglycerides, and cholesterol in the liver. The livers of chicks fed on taurine diets at $34^{\circ}C$ showed significantly higher proportions of C14:0, C16:1, C18:1, C18:2, and 20:3, and lower C18:0 and C20:4 proportions than those of chicks fed on control diets at the same temperature (p<0.05). The total levels of saturated fatty acids decreased, but monounsaturated fatty acids and unsaturated fatty acid levels increased in chicks fed the taurine diet, as compared to chicks fed the control diet at $34^{\circ}C$ (p<0.05). Peroxidizability indices were significantly lower in the heat-exposed chicks fed the taurine diet than in the non-taurine heat-exposed groups (p<0.05). In conclusion, dietary taurine results in an increase in the growth performances of chicks under heat stress conditions via improvements in lipid absorption and metabolism, as well as an induced reduction in lipid peroxidation.

• Korean Journal of Medicinal Crop Science
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• v.10 no.1
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• pp.29-36
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• 2002

Epimedium koreanum Nakai(EKN) has traditionally been well-known as a herbal medicine for the promotion of stamina and the improving sexual activity of human in oriental countries including Korea and China. The aim of this study was to investigate the effect of dietary supplementation of EKN water-extract(0.025%,w/v) on age-related change of xenobiotic metabolizing system in rat liver. Long-term supply of the EKN extract to rats did not induce any discernible signs. However, the mass of liver and kidney were slightly increased by the dietary supplementation. Level of cytochrome P450, NADPH cytochrome P450 reductase, P450 dependent ethoxycoumarin O-deethylase benzphetamine N-demethylase and glutathione-S-transferase in liver were decreased with age, but, these activities in 24 months of age were declined more in rats supplied with EKN extract. Level of cytochrome b5 and NADH-cytochrome b5 reductase were also decreased with age, however, there was no significant difference between with and without EKN extract. These results indicate that long-term supplementation of EKN extract to rats from weaning to 24 months may be a burden on the liver function in old age, and may aggregate the decline of xenobiotic metabolizing enzymes activities in old age.

• Applied Biological Chemistry
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• v.42 no.1
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• pp.29-33
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• 1999

To investigate the effects of Angelica gigas Nakai diet on lipid metabolism, alcohol metabolism and liver function of rats administered with chronic ethanol, Sprague-Dawley male rats were fed either AIN-76 diet (control), control diet with ethanol, control plus Angelica gigas Nakai diet, or control plus Angelica gigas Nakai diet with ethanol for 30 days. On the 21st day, all of the rats were given an oral dose of ethanol and blood-ethanol concentration was monitored for the next 5 hours. The results obtained were: 1) Upon ethanol administration, the blood ethanol concentration was decreased from 2 hr significantly in the group of control plus Angelica gigas Nakai diet compared with control diet group; 2) The blood ethanol oxidation rate was increased in the group of control plus Angelica gigas Nakai diet with ethanol compared with control diet group or control plus Angelica gigas Nakai diet group. After 30 days, rats were sacrificed and then lipid and enzyme determinations in blood and liver were carried out. The results obtained were: 1) LDL-cholesterol in the blood of control plus Angelica gigas Nakai diet group was decreased significantly compared with control diet group; 2) Angelica gigas Nakai diet decreased liver triglyceride and total lipid and blood ${\gamma}-GTP$ level increased due to the chronic ethanol administration. These data suggest that Angelica gigas Nakai can have a recovery function on the symptoms of alcohol related diseases.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.392-402
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• 2017

Background: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. Methods: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides. $H_2O_2$ productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and small interfering RNA (siRNA) transfection. Results and conclusion: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-$\text\tiny L$-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S-PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.

• Korean Journal of Food Science and Technology
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• v.31 no.6
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• pp.1661-1666
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• 1999

Yungmijihwgang-Won, Yollyunggobon-Dan and Palmi-Hwan, Korea traditional prescriptions composed of oriental medical herbs, have been used successfully to improve human health and regimen. This study was designed to examine the mechanism of healthful effects of the Korea traditional prescriptions through its antioxidative potentials. Using in vitro antioxidative activity assay system such as DPPH radical quenching assay, superoxide anion radical scavenging assay and inhibition of TBARS production, three Korea traditional prescriptions were observed to have nearly the same antioxidative potentials as ascorbic acid, a well-known strong water-soluble antioxidant. Moreover, we observed reinforced antioxidative effects of these drugs in liver from mouse fed these drugs with 4 weeks. When liver homogenate was incubated with 2.2'-azobis(amidinopropane) dihydrochloride(AAPH), as a free radical initiator, we observed that oxidative damages were decreased and antioxidative potentials were increased in liver homogenate treated these drugs. However, enzymatic antioxidative system as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was not affected by drug administration.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.11
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• pp.1499-1505
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• 2009

This study investigated the effect of improved liver function in rats administered with ethanol by kimchi lactic acid bacteria with high GABA producing capacity. Sprague-Dawley male rats were divided into four groups; normal diet control (NC), ethanol control (EC), ethanol＋Lactobacillus sp. OPK2-59 normal powder (EL1), ethanol＋Lactobacillus sp. OPK2-59 GABA powder (EL2) and fed for 6 weeks. Analysis showed that there were no significant differences in body weight and feed consumption among the groups during the experimental period. Also, there were no significant differences in organ weight among the groups. The test results showed total cholesterol and triglyceride in the blood concentration that were increased by ethanol administration were significantly lowered in EL2 group. Liver triglyceride was also significantly lowered in the EL2 group compared with the EC group. Serum GOT and GPT, and liver GOT levels were significantly lower in the EL2 group compared with the EC group. Serum ethanol concentration was lower in the EL1 and EL2 groups compared with the EC group. SOD activities in liver were significantly increased in the EL1 and EL2 groups compared with the EC group. These results suggest that Lactobacillus sp. OPK2-59 GABA powder improves lipid and enzyme profiles of rats administered with ethanol.

• Journal of Nutrition and Health
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• v.44 no.1
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• pp.5-15
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• 2011

Although iron is an essential mineral, excess iron intake during pregnancy may increase oxidative stress in tissues. This study was conducted to investigate the effects of iron overload during pregnancy on iron status and oxidative stress in maternal rats. Ten week-old female Sprague-Dawley rats were mated with male rats. Non-pregnant (control) and pregnant rats were fed diets containing normal Fe (35 mg/kg diet), high Fe (350 mg/kg diet), or excess Fe (1,050 mg/kg diet) during pregnancy. Rats were sacrificed on pregnancy day 19. No significant difference in weight gain, diet intake, or litter size was observed according to iron intake levels. Furthermore, serum iron, hemoglobin, and hematocrit were not different among the rats administered the three levels of Fe both in the control and pregnant groups. However, the iron levels were lower in pregnant rats than those in the control. The liver and spleen iron contents increased significantly in the excess Fe group. An increase in liver ferritin levels with increasing iron intake was observed. Protein carbonyl content, as a marker of oxidative stress, increased significantly in liver with increasing iron intake but not malondialdehyde. Glutathione peroxidase activity in the liver of pregnant rats fed excess iron decreased significantly. Bcl-2 protein expression in the liver declined remarkably with increasing maternal iron intake in pregnant rats. Taken together, iron overload during pregnancy had little effect on hematology. However, the deposits of iron in the liver and the decline in antioxidant enzyme activity implied increased oxidative stress in tissues of the excess Fe group. These results suggest that excess iron intake during pregnancy increases oxidative stress in maternal tissues and may also affect fetal tissues.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.418-427
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• 2003

Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.