• Title/Summary/Keyword: ob/ob mouse

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Effects of Ojung-hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in Ob/ob Mouse (Ob/ob mouse에서 오정환(五精丸)이 혈당, 고지혈증, Polyol Pathway 및 항산화작용에 미치는 영향)

  • Gong, Tae-Hyun;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.28 no.3 s.71
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    • pp.57-69
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    • 2007
  • Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications have shown that oxidative stress might play a major role. Therefore, many methods have been tried to regulate free oxygen radicals for treating diabetes and its complications. Ojung-hwan, composed of five crude herbs, has been considered effective for treating symptoms of aging. In male ob/ob mouse of severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activities and mechanisms of Ojung-hwan were examined. Methods : Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. The effects of Ojung-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical (${\cdot}\;O{_2}{^-}$), MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Results : Ojung-hwan lowered the levels of serum glucose and insulin in a dose-dependent manner. Total cholesterol, triglyceride and free fatty acid levels decreased, while the HDL-cholesterol level increased, in Ojung-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities increased in the ob/ob mice, whereas they were inhibited in the Ojung-hwan treated groups. Ojung-hwan inhibited the generation of ${\cdot}\;O{_2}{^-}$ in the kidney. Finally, MDA+HAE levels increased and GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Ojung-hwan treated groups. Conclusions : Ojung-hwan showed antidiabetic and antihyperlipidemic activities by regulating theactivities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

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Effects of Cheonghyul-san on Blood Glucose, Hyperlipidemia, Polyol Pathway and Reactive Oxygen Species in ob/ob Mice (청혈산(淸血散)이 ob/ob mouse의 혈당, 고지혈증, Polyol Pathway 및 Reactive Oxygen Species에 미치는 영향)

  • Park, Sang-Tae;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.2
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    • pp.350-356
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    • 2008
  • Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Cheonghyul-san has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs. In male ob/ob mouse with severe obesity, hyperinsulinemia, hypergiycemia, hyperlipidemia, the acting mechanisms of Cheonghyul-san were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Cheonghyul-san per 1 kg of body weight for 14 days. The effects of Cheonghyul-san extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Cheonghyul-san lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Cheonghyul-san treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Cheonghyul-san-administered groups. Cheonghyul-san inhibited the generation of ROS in the kidney. Finally, MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Cheonghyul-san-administered groups. The results suggested that Cheonghyul-san exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging ROS, regulating the MDA+HAE and GSH levels in the ob/ob mice.

Effects of Sotosajahwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse (소토사자환이 ob/ob mouse의 혈당, 고지혈증, Polyol Pathway 및 항산화작용에 미치는 영향)

  • Park, Seong-Ho;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1163-1169
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    • 2007
  • Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

Effects of Mori Fructus Extract on Hyperglycemia, Hyperlipidemia, Polyol Pathway, AGE and RAGE in ob/ob Mice (상침자(桑椹子)추출물이 ob/ob mouse의 혈당, 혈청 지질, Polyol Pathway, AGE 및 RAGE에 미치는 영향)

  • Lee, Min-Dong;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.351-359
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    • 2009
  • Etiological studies of diabetes and its complications showed that oxidative stress might play a major role, Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Mori Fructus extract has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs, The aim of this study was to investigate the effect of Mori Fructus extract in male ob/ob mouse with severe obesity, hyperinsulinemia, hyperglycemia, hyperlipidemia. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57BL/6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus extract per 1 kg of body weight for 14 days. The effects of Mori Fructus extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Western blotting was performed using anti-AGE, anti-RAGE respectively. Mori Fructus extract lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Mori Fructus extract treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the generation of ROS in the kidney. MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the expression of AGE, RAGE in the ob/ob mice. The results suggested that Mori Fructus exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging the ROS, decreasing the MDA+HAE level, increasing the GSH level and inhibiting the expression of AGE, RAGE in the ob/ob mice.

The Effect of Magnolia Bark on the Metabolic Inflammation and Insulin Resistance of ob/ob Mice (후박(厚朴)이 ob/ob 마우스의 대사성 염증과 인슐린 저항성에 미치는 영향 및 관련기전에 대한 연구)

  • Kim, Hyo-jae;Kim, Eun-ji;Ma, Young-hoon;Han, Yang-hee
    • The Journal of Internal Korean Medicine
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    • v.39 no.4
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    • pp.751-763
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    • 2018
  • Objective: This study was undertaken to investigate how magnolia bark extract affects ob/ob mouse in terms of metabolic inflammation and insulin resistance. Methods: Leptin-deficient ob/ob mice were divided into 2 groups (n=5): a normal saline treatment (=control) and magnolia bark treatment. Wild type mice were the lean group (n=5). After 5 weeks, we measured fasting blood sugar (FBS) and conducted oral glucose tolerance tests (OGTTs) in each group. After 6 weeks, we measured body weight, epididymal fat pad weight, liver weight, serum glucose, serum insulin, and gene expression of tumor necrosis factor-${\alpha}$, interferon-${\gamma}$, and interleukin-6. We characterized the phenotype of adipose tissue macrophages (ATMs) and analyzed fractions of the phenotype in each group by flow cytometry. Results: In the magnolia bark group, fasting blood sugar, oral glucose tolerance levels, and insulin resistance (HOMA-IR) were significantly decreased. The population and proportion of ATMs among leukocytes in adipose tissue were significantly decreased in the magnolia bark group. The population and proportion of M1 type ATMs among ATMs were significantly decreased in the magnolia bark group. Gene expression of tumor necrosis factor-${\alpha}$ was significantly decreased in the magnolia bark group. Conclusions: These results support a positive effect of magnolia bark on metabolic diseases such as insulin resistance and metabolic inflammation in leptin-deficient ob/ob mice.

Liver Plasma Membrane and Nuclear $T_{3}$ Receptor Binding in the Obese (ob/ob) Mouse (비만 쥐(ob/ob mouse)의 간 세포막과 핵에 있는 $T_{3}$ 수용체의 결합능력에 관한 연구)

  • Kim, Kyung-Ah;Lachance, Paul A.
    • Journal of Nutrition and Health
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    • v.24 no.4
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    • pp.356-365
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    • 1991
  • $L-Triiodothyronine(T_3)$ binding to purified plasma membrane and to isolated nuclei from the same liver in obese(ob/ob) mice and their lean littermates was examined. The maximal binding capacity(Bmax) for $T_3$ receptor of liver nuclei, as compared to lean control, was significantly lower in the obese mouse$(obese 527{\pm}80fmol/mg\;DNA ; lean 883{\pm}62fmol/mg\;DNA)$, without an apparent difference in dissociation constant(Kd). The finding that obese mice have fewer liver nuclear $T_3$ receptors confirms previous reports. The Bmax and Kd of liver plasma membrane $T_3$ receptor were not significantly different between obese and lean mouse, which suggests no defect to be occurring in the function of the plasma membrane $T_3$ receptor and reinforces the view that the peripherally impaired thyroid hormone action in obese mice is a post plasma membrane receptor event. These results further support the hypothesis that the major defect of the thyroid hormone metabolism in genetic obesity occurs at the level of the nuclear receptor.

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Effects of Sotosaja-hwan on the Generation of ROS, RNS, and on the Expression of NF-${\kappa}B$-dependent Proteins in ob/ob Mouse (소도사자환이 ob/ob mouse에서 ROS/ RNS 생성 억제 및 NF-${\kappa}B$ 의존성 단백질에 미치는 영향)

  • Bang, Yong-Suk;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.51-63
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    • 2009
  • Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

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Proteomic Analysis in ob/ob Mice Before and After Hypoglycemic Polysaccharide Treatments

  • Kim, Sang-Woo;Hwang, Hye-Jin;Baek, Yu-Mi;Hwang, Hee-Sun;Yun, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • v.19 no.10
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    • pp.1109-1121
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    • 2009
  • In an attempt to discover novel biomarker proteins in type 2 diabetes prognosis, we investigated the influence of hypoglycemic extracellular polysaccharides (EPS) obtained from the macrofungus Tremella fuciformis on the differential levels of plasma proteins in ob/ob mice using two-dimensional gel electrophoresis (2-DE). The 2-DE analysis demonstrated that 92 spots from about 900 visualized spots were differentially regulated, of which 40 spots were identified as principal diabetes-associated proteins. By comparing control with EPS-fed mice, we found that at least six proteins were significantly altered in ob/ob mice, including Apo A-I, IV, C-III, E, retinol-binding protein 4, and transferrin, and their levels were interestingly normalized after EPS treatment. Western blot analysis revealed that the altered levels of the two regulatory molecules highlighted in diabetes and obesity (e.g., resistin and adiponectin) were also normalized in response to EPS. The Mouse Diabetes PCR Array profiles showed that the expression of 84 genes related to the onset, development, and progression of diabetes were significantly downregulated in liver, adipocyte, and muscle of ob/ob mice. EPS might act as a potent regulator of gene expression for a wide variety of genes in ob/ob mice, particularly in obesity, insulin resistance, and complications from diabetes mellitus.