• 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.

• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.103-112
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• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.419-428
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• 2018

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.108-118
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• 2021

Background: Korean ginseng (Panax ginseng Meyer) contains a variety of ginsenosides that can be metabolized to a biologically active substance, compound K. Previous research showed that compound K could be enriched in the red ginseng extract (RGE) after hydrolysis by pectinase. The current study investigated whether the enzymatically hydrolyzed red ginseng extract (HRGE) containing a notable level of compound K has cognitive improving and neuroprotective effects. Methods: A scopolamine-induced hypomnesic mouse model was subjected to behavioral tasks, such as the Y-maze, passive avoidance, and the Morris water maze tests. After sacrificing the mice, the brains were collected, histologically examined (hematoxylin and eosin staining), and the expressions of antioxidant proteins analyzed by western blot. Results: Behavioral assessment indicated that the oral administration of HRGE at a dosage of 300 mg/kg body weight reversed scopolamine-induced learning and memory deficits. Histological examination demonstrated that the hippocampal damage observed in scopolamine-treated mouse brains was reduced by HRGE administration. In addition, HRGE administration increased the expression of nuclear-factor-E2-related factor 2 and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase and heme oxygenase-1 in hippocampal tissue homogenates. An in vitro assay using HT22 mouse hippocampal neuronal cells demonstrated that HRGE treatment attenuated glutamate-induced cytotoxicity by decreasing the intracellular levels of reactive oxygen species. Conclusion: These findings suggest that HRGE administration can effectively alleviate hippocampus-mediated cognitive impairment, possibly through cytoprotective mechanisms, preventing oxidative-stress-induced neuronal cell death via the upregulation of phase 2 antioxidant molecules.

• Journal of Ginseng Research
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• v.48 no.5
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• pp.481-493
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• 2024

Background: Post-weaning social isolation (SI) reduces sociability, gene expressions including myelin genes in the medial prefrontal cortex (mPFC), and alters microbiome compositions in rodent models. Korean Red Ginseng (KRG) and its major ginsenoside Rb1 have been reported to affect myelin formation and gut metabolites. However, their effects under post-weaning SI have not been investigated. This study investigated the effects of KRG and Rb1 on sociability, gene expressions in the mPFC, and gut metabolites under post-weaning SI. Methods: C57BL/6J mice were administered with water or KRG (150, 400 mg/kg) or Rb1 (0.1 mg/kg) under SI or regular environment (RE) for 2 weeks during the post-weaning period (P21-P35). After this period, mice underwent a sociability test, and then brains and ceca were collected for qPCR/immunohistochemistry and nontargeted metabolomics, respectively. Results: SI reduced sociability compared to RE; however, KRG (400 mg/kg) and Rb1 significantly restored sociability under SI. In the mPFC, expressions of genes related to myelin, neurotransmitter, and oxidative stress were significantly reduced in mice under SI compared to RE conditions. Under SI, KRG and Rb1 recovered the altered expressions of several genes in the mPFC. In gut metabolomics, 313 metabolites were identified as significant among 3027 detected metabolites. Among the significantly changed metabolites in SI, some were recovered by KRG or Rb1, including metabolites related to stress axis, inflammation, and DNA damage. Conclusion: Altered sociability, gene expression levels in the mPFC, and gut metabolites induced by two weeks of post-weaning SI were at least partially recovered by KRG and Rb1.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.544-549
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• 2014

BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance is a strong risk factor for type 2 diabetes mellitus. The aim of this study was to investigate the effect of myricetin on adiposity, insulin resistance, and inflammatory markers in mice with diet-induced insulin resistance. MATERIALS/METHODS: Five-week-old male C57BL/6J mice were fed a basal diet, a high-fat, high-sucrose (HFHS) diet, or the HFHS diet containing 0.06% myricetin or 0.12% myricetin for 12 weeks after a 1-week adaptation, and body weight and food intake were monitored. After sacrifice, serum lipid profiles, glucose, insulin, adipocyte-derived hormones, and proinflammatory cytokines were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. RESULTS: Myricetin given at 0.12% of the total diet significantly reduced body weight, weight gain, and epidydimal white adipose tissue weight, and improved hypertriglyceridemia and hypercholesterolemia without a significant influence on food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, decreased significantly by 0.12% myricetin supplementation in mice fed the HFHS diet. Myricetin given at 0.12% of the total diet significantly reduced serum levels of leptin, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) in mice fed the HFHS diet. CONCLUSIONS: These findings suggest that myricetin may have a protective effect against diet-induced obesity and insulin resistance in mice fed HFHS diet, and that alleviation of insulin resistance could partly occur by improving obesity and reducing serum proinflammatory cytokine levels.

• The Journal of Internal Korean Medicine
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• v.35 no.2
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• pp.119-132
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• 2014

Objectives : This study was undertaken to investigate the effects of Samulhwalhyeol-tang (SM) in a hyperlipidemic animal model induced by a high-fat diet using diverse biological methods. Methods : This study was to determine whether fractionated EtOH extracts of SM inhibit reactive oxygen species (ROS) and nitric oxide (NO) in RAW 264.7 cells. Hyperlipidemia was induced by a high-fat diet fed for 6 weeks. Total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, glucose, liver function, cholesterol gene revelation control efficiency, and histologic change of liver were measured after oral administration of SM. Results : 1. Compared to the control group, ROS production (%) and NO production (%) were decreased significantly by SM. 2. Total cholesterol, LDL cholesterol, triglyceride were decreased significantly by SM. 3. HDL cholesterol was increased significantly by SM. 4. Rats' body weight and glucose were decreased significantly by SM. 5. AST, ALP were decreased significantly by SM. 6. In histopathologic examination, fatty liver and fiver fibrosis were inhibited, almost eliminated as round of fat was observed in the liver. Conclusions : SM would appear that effective in the prevention and treatment of atherosclerosis, ischemic heart disease, other cardiovascular diseases, fatty liver and nephrotic syndrome caused by hyperlipidemia.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.94-103
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• 2008

Objectives: The aim of this study was to determine whether celastrol, the triterpenoid component of Celastrus orbiculatus, offers neuroprotection against Parkinson's disease (PD) in mice administered 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine(MPTP). Methods: We examined how celastrol affected MPTP-induced neuronal loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) in the midbrain of mice. C57BL/6J mice were divided into four groups: (1) saline-saline, (2) saline-celastrol, (3) MPTP-saline, and (4) MPTP-celastrol. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (18mg/kg) at 2 h intervals and then i.p. administered celastrol (3mg/kg) two times at 12 h after last celastrol administration. Expression of TH on the SNpc of brain tissues were analyzed at 7 days after the treatments by immunohistochemistry and Western blot. Results: Immunohistochemical analysis using TH antibody showed that celastrol provided significantly protective effects against MPTP-induced loss of TH-positive dopaminergic neurons in the SNpc region of the midbrain of mice. Our Western blot study also showed that celastrol significantly inhibits the MPTP-induced neuronal damage via the up-regulation of TH protein levels in MPTP mice. Conclusions: The present results suggest that it may be possible to use celastrol for the prevention of nigral degenerative disorders including PD, caused by exposure to toxic substances.

• The Journal of Korean Medicine
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• v.39 no.2
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• pp.1-12
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• 2018

Objectives: The objective of this study is to develop a new animal model with Kidney-hypofunction for Sasang Constitutional Medicine, especially for partial Soyangin(one of four constitution which has good digestive function and poor renal function) by Unilateral Ureteral Obstruction, and to estimate the factor related to obesity, dyslipidemia, and metabolic syndrome. Methods: The C57BL/6J mice were divided into 3 groups : normal group, high fat diet(HFD) control group, and HFD group with Unilateral Ureteral Obstruction(UUO). Then, the HFD control group and the experimental group were fed with high fat diet for 6 weeks. Food intake and body weight were measured at regular time by week. After the final experiment, blood was gathered for bloodchemical examination and organs(liver, fatty tissue) were remoed, weighted, and mRNA was analyzed with real-time PCR. Results: The weight growth rate with High fat diet went down by 8.35% in experimental group and had similar FER with the normal group, while HFD control group had higher weight growth rate and FER than any other groups. Also The experimental group had lower triglyceride and LDL cholesterol rate and higher glucose rate in serum. and in mRNA expression, GLUT-9, the protein related to excretion of uric acid and metabolic syndrome, expressed lower rate than that of HFD control group. and IL-6, a kind of cytokine related to obesity and metabolic syndrome, expressed more than HFD control group. Conclusions: It was found that Kidney-hypofunction animal-experimental model is susceptible to metabolic syndrome.

• Nutrition Research and Practice
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• v.6 no.3
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• pp.201-207
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• 2012

This study investigated the hypoglycemic, hypolipidemic, and antioxidant effects of dietary quercetin in an animal model of type 2 diabetes mellitus. Four-week-old C57BL/KsJ-db/db mice (n = 18) were offered an AIN-93G diet or a diet containing quercetin at 0.04% (low quercetin, LQE) or 0.08% of the diet (high quercetin, HQE) for 6 weeks after 1 week of adaptation. Plasma glucose, insulin, adiponectin, and lipid profiles, and lipid peroxidation of the liver were determined. Plasma glucose levels were significantly lower in the LQE group than in the control group, and those in the HQE group were even further reduced compared with the LQE group. The homeostasis model assessment for insulin resistance (HOMA-IR) showed lower values for LQE and HQE than for the control group without significant influence on insulin levels. High quercetin increased plasma adiponectin compared with the control group. Plasma triglycerides in the LQE and HQE groups were lower than those in the control group. Supplementation with high quercetin decreased plasma total cholesterol and increased HDL-cholesterol compared with the control group. Consumption of low and high quercetin reduced thiobarbituric acid reactive substances (TBARS) levels and elevated activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver. Thus, quercetin could be effective in improving hyperglycemia, dyslipidemia, and antioxidant status in type 2 diabetes.