• 대한의생명과학회지
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• 제12권2호
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• pp.65-72
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• 2006

Thiazolidinediones (TZDs) are widely used antidiabetic drugs that activate the nuclear peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$, and thereby improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin resistance, and cardiovascular disease. To determine whether the $PPAR{\gamma}$ ligand troglitazone regulates lipid metabolism with sexual dimorphism, we examined the effects of troglitazone on circulating lipids, body weight and the expression of hepatic genes responsible for lipid metabolism in both sexes of C57BL/6J mice. Compared to mice fed a low fat control diet, both sexes of mice fed a troglitazone-treated low fat diet for 14 weeks did not exhibit changes in body weight gain, serum total cholesterol, HDL-cholesterol and LDL-cholesterol levels. However, serum triglycerides were significantly reduced in both sexes of mice, although these effects were more pronounced among males. Furthermore, troglitazone regulated the expression of hepatic genes critical for lipid and lipoprotein metabolism, the magnitudes of which were much higher in males compared to females, as evidenced by results for increased acyl-CoA oxidase and decreased apolipoprotein C-III mRMA levels. These results suggest that $PPAR{\gamma}$ activator troglitazone may exert sexually dimorphic control of serum triglycerides in part through the differential activation of $PPAR{\gamma}$ in liver between male and female mice.

• 대한의생명과학회지
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• 제24권4호
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• pp.311-318
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• 2018

Vitamin C (ascorbic acid) supplementation has been suggested to negatively correlate with obesity in humans and other animals. Previous studies, including ours, have demonstrated that a high-fat diet (HFD) induces obesity and related diseases such as hyperlipidemia, hyperglycemia, insulin resistance, and nonalcoholic fatty liver disease. Here, we investigated the effects of vitamin C on visceral adipocyte hypertrophy and glucose intolerance in C57BL/6J mice. Mice received a low-fat diet (LFD, 10% kcal fat), HFD (45% kcal fat), or the same HFD supplemented with vitamin C (HFD-VC, 1% w/w) for 15 weeks. Visceral adiposity and glucose intolerance were examined using metabolic measurements, histology, and gene expression analyses. Mice in the HFD-VC supplementation group had reduced body weight, mesenteric fat mass, and mesenteric adipocyte size compared with HFD-fed mice. Vitamin C intake in obese mice also decreased the mRNA levels of lipogenesis-related genes (i.e., stearoyl-CoA desaturase 1 and sterol regulatory element-binding protein 1c) in mesenteric adipose tissues, inhibited hyperglycemia, and improved glucose tolerance. In addition, vitamin C attenuated the HFD-induced increase in the size of pancreatic islets. These results suggest that vitamin C suppresses HFD-induced visceral adipocyte hypertrophy and glucose intolerance in part by decreasing the visceral adipose expression of genes involved in lipogenesis.

• 대한한방내과학회지
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• 제30권2호
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• pp.410-421
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• 2009

Objective : The aim of this study is to investigate the preventive effect of Injinchunggan-tang (YJCGT) & Injinysaryung-san (YJSRS) on MCD-diet-induced NASH in A/J mice. Methods : A/J mice were divided into 4 groups: Normal group (normal diet without any treatment). Control group (MCD diet only), YJCGT group (MCD diet with YJCGT), and YJSRS group (MCD diet with YJSRS). After 5 weeks, body weight, liver weight, biochemical parameters for liver function test, histological changes, and real-time PCR were assessed. Results : Mice lost body weight with the MCD diet and the YJCGT and YJSRS groups lost less than the control group, though showed no statistical significance. Liver weights were decreased by the MCD diet, but not significantly. In the liver function test, all the values were increased with the MCD diet, though some did not show significance. Alp and ALT levels were significantly less increased by YJCGT compared to the normal (p<0.05). All values were decreased or increased compared to the control by treatment though showed no significance possibly due to insufficient sample numbers. In histological findings of the livers. MCD-diet induced severe fatty change and collagen accumulation in the livers, but this fatty change was reduced in the YJCGT and YJYRS groups and fibrogenesis was inhibited significantly with p<0.05 and p<0.01, respectively. In real-time PCR analysis, YJCGT and YJYRS showed inhibitory effect on liver fibrogenesis by reducing associated gene expressions caused by MCD diet. Conclusion : YJCGT and YJSRS are considered to be possible candidates for the treatment of patients with NASH and/or liver fibrosis.

• 대한의생명과학회지
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• 제18권3호
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• pp.227-236
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• 2012

Previous study showed that swimming improved obesity but was not through $PPAR{\alpha}$ activation in liver and skeletal muscle in high fat diet-fed female mice with functioning ovaries as an animal model of obese premenopausal women. Thus, this study was aimed at investigation of the effects of swimming on the promotion of health and its molecular mechanism in adipose tissue of high fat diet-fed female mice. Eight-week-old female C57BL/6J mice were randomly divided into two groups (a non-swim control group and a swim group, n=8/group). Mice in the swim group swam for 2 h daily for 6 weeks in water bath with temperature of $35{\pm}1^{\circ}C$. All the animals received high fat diet (45% kcal fat) for 6 weeks. Reverse transcription-polymerase chain reaction was used to elucidate the molecular mechanism. Female mice subjected to swimming had significantly decreased body weight gain and white adipose tissue mass compared with the female control mice. Histological studies illustrated that swimming decreases the hepatic lipid accumulation. As expected, swimming did not affect the expression of mRNA levels of peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 and medium chain acyl-CoA dehydrogenase in the white adipose tissue. However, mice that underwent 6-weeks of swimming exercise had decreased the mRNA expression of lipogenic genes, such as sterol regulatory element-binding proteins-1C and fatty acid synthase in comparison to sedentary control mice, with decreased $PPAR{\gamma}$ target genes involved in adipocyte-specific marker genes, such as adipocyte fatty acid binding protein and leptin in the white adipose tissue. These results suggest that swimming can effectively prevent obesity induced by high fat diet-fed, in part through down-regulation of adipogenesis and lipogenesis in white adipose tissue of female obese mice. Moreover, these results suggest that swimming maybe contributing the promotion of health through regulation of adipogenesis and lipogenesis in overweight premenopausal women.

• 혜화의학회지
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• 제20권1호
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• pp.11-23
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• 2011

Systemic Lupus Erythematosus(SLE) is an autoimmune disease invading the skin, joint, kidney, intestinal membrane, neurosystem and other organs. SLE is an autoimmune disease characterized by immune dysregulation resulting in the production of antinuclear antibodies(ANA), generation of circulating immune complexes, and activation of the complement system. In Korean medicine, lupus can be classified as acute arthritis, reddish butterfly erythema, asthenic disease, edema and so on. The cause and procedure of the diseases are flourishing noxious heat, excessive fire due to deficiency of yin, blood stasis due to stagnation of qi, internal movement of the liver-wind, congenital deficiency, exhausted vital-qi, which are treated by clearing away heat and cooling the blood, nourshing yin and extinguishing fire, treating flatulence and activating blood circulation, nourishing the blood to expel wind, invigorating the liver and kidney, invigorating qi and replenishing the blood. To experimentally examine the influence of Insam-Buja-Tang (Ginseng & Aconiti Extract, IBT) on the outbreak and development of lupus, lupus induce MRL/MpJ-Faslpr lupus-prone mice model was used. As IBT was orally administrated to a lupus model mouse, various tests such as the weight, urine protein, renal function, Lymph cell test of the spleen, Cytokine expression, histopathological analysis of kideny were performed to see the influence on the kidney and whether it work effectively on the immune function. The main purpose of this study is to evaluate the effect of IBT on MRL/MpJ-Faslpr lupus-prone mice model. The effect of IBT on MRL/MpJ-Faslpr lupus-prone mice that can have autoimmune disease similar to SLE in human was evaluated after IBT per oral in the present study.

• 대한수의학회지
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• 제48권3호
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• pp.327-336
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• 2008

Many herbal extracts have been reported to have a preventive or therapeutic effect of on diabetes mellitus. Momordica Charantia commonly known as bitter melon or karela has been reported to be a medicinal plant for treating various diseases including cancers and diabetes. The objectives of this study were to investigate anti-diabetic effects of bitter melon (BM) as determined by blood glucose levels, glucose tolerance test (GTT), insulin tolerance test (ITT), insulin and HbA1C activities in serum, serum biochemical and lipid levels, histopathology, immunohistochemistry and AMPK-${\alpha}2$ expression of skeletal muscle in male C57BL/6J db/db mice. There were four experimental groups including vehicle control, BM 10 mg/kg, BM 50 mg/kg, and BM 250 mg/kg. BM at doses of 10, 50, and 250 mg/kg was orally administered to the diabetic mice everyday for 8 weeks. The treatments of BM 10, 50, and 250 mg/kg significantly decreased the blood glucose level in the diabetic mice compared with vehicle control (p < 0.05). The treatments of BM 10 and 50 mg/kg significantly decreased the GTT, ITT and HbA1c levels in the diabetic mice compared with vehicle control (p < 0.05). All BM groups significantly decreased GOT, GPT, BUN, LDL and glucose levels in the diabetic mice compared with the vehicle control mice (p < 0.05). The livers of mice treated with the BM 10, 50, and 250 mg/kg showed a remarkable decrease in the number of lipid droplets compared with the vehicle control. The pancreas of mice treated with the BM 10, 50, and 250 mg/kg showed a remarkable increase in insulin concentration of ${\beta}$-cells compared with the vehicle control. In addition, the treatments of BM 10, 50, and 250 mg/kg actually increased the expression of AMPK-${\alpha}2$ compared with vehicle control. These results suggest that BM has a respectable anti-diabetic effect resulting from inhibition of blood glucose level and lipid level in serum and that consumption of BM may give a benefit for controlling diabetes mellitus in humans.

• 한국응용과학기술학회지
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• 제34권3호
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• pp.427-435
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• 2017

제니스테인(genistein)이 폐경으로 유도된 비만을 조절하는지를 알아보기 위해 폐경기 여성의 동물모델인 난소절제 암컷 쥐에서 항비만 효과에 대한 제니스테인의 영향을 연구하였다. 7주령의 C57BL/6J 암컷쥐를 무작위로 3그룹으로 나누어 8주 동안 고지방식 사료 또는 제니스테인이 첨가된 고지방식 사료를 섭취시킨 후 비만의 결정요소들을 측정하였다. 난소절제 쥐는 난소가 절제되지 않은 쥐에 비해 몸무게와 지방조직무게가 증가되었다. 그러나 제니스테인의 처리는 난소절제 쥐의 몸무게, 지방조직무게 및 지방세포 크기를 감소시켰다. 난소절제 쥐에 비해 제니스테인이 처리된 난소절제 쥐는 혈청 속의 중성지방과 총 콜레스테롤이 유의적으로 낮아졌다. 또한 난소절제 쥐에서 간조직의 지질성분 축적도 제니스테인에 의해 감소되었다. 이러한 결과는 제니스테인이 난소절제로 유도된 지방과다, 지방세포비대 및 지질이상을 효과적으로 개선시킬 수 있다는 것을 시사하고 있다. 따라서 본 연구는 폐경기 여성의 비만과 고지혈증을 포함한 신진대사 장애의 개선에 공헌할 것이다.

• Journal of Radiation Protection and Research
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• 제38권4호
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• pp.166-171
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• 2013

While high-dose ionizing radiation results in long term cellular cytotoxicity, chronic low-dose (<0.2 Gy) of X- or ${\gamma}$-ray irradiation can be beneficial to living organisms by inducing radiation hormesis, stimulating immune function, and adaptive responses. During chronic low-dose-rate radiation (LDR) exposure, whole body of mice is exposed to radiation, however, it remains unclear if LDR causes changes in gene expression of the whole brain. Therefore, we aim to investigate expressed genes (EGs) and signaling pathways specifically regulated by LDR-irradiation ($^{137}Cs$, a cumulative dose of 1.7 Gy for total 100 days) in the whole brain. Using microarray analysis of whole brain RNA extracts harvested from ICR and AKR/J mice after LDR-irradiation, we discovered that two mice strains displayed distinct gene regulation patterns upon LDR-irradiation. In ICR mice, genes involved in ion transport, transition metal ion transport, and developmental cell growth were turned on while, in AKR/J mice, genes involved in sensory perception, cognition, olfactory transduction, G-protein coupled receptor pathways, inflammatory response, proteolysis, and base excision repair were found to be affected by LDR. We validated LDR-sensitive EGs by qPCR and confirmed specific upregulation of S100a7a, Olfr624, and Gm4868 genes in AKR/J mice whole brain. Therefore, our data provide the first report of genetic changes regulated by LDR in the mouse whole brain, which may affect several aspects of brain function.

• Journal of Ginseng Research
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• 제32권3호
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• 한국환경보건학회지
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• 제38권6호
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• pp.541-549
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• 2012

Objectives: This study was undertaken in order to evaluate a potential mechanism involved in gastro-intestinal problems observed in autistic subjects and uses an animal model of autism investigation. Methods: BTBR T+tf/J, a mouse strain with typical socio-behavioral characteristics of autistic subjects and FVB mice with highly social behaviors as the control strain were used. Both genders of mice aged three weeks and six months were used from four separate litters for each strain. Serum was prepared following cardiac puncture, and mesenteric lymph nodes were collected for in vitro stimulation and enumeration of major immune cell proportion. Results: The level of serum IgA was significantly enhanced in six-month-old BTBR mice compared with three-week-old BTBR, which was not observed with the FVB control mice. The serum IgE level was also higher among BTBR mice than among age-sex matched FVB mice, respectively. Considering the ratio of interleukin-4 vs interferon-gamma production from mesenteric lymph node T cells, skewedness toward type-2 reactivities was observed. In addition, the proportion of B cells in mesenteric lymph nodes was significantly higher in BTBR mice than in FVB mice. Conclusion: Upregulation of mucosal immunity related with enhanced type-2 immune reactivity observed in BTBR mice could be involved with the etiology of gastro-intestinal abnormalities in autism.