• Proceedings of the Ginseng society Conference
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• 2007.12a
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA 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 RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.452-458
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• 2008

The effect of fermented soybean culture of Bacillus subtilis MORI mixed with mulberry leaves on the lowering the levels of blood glucose and cholesterol was examined using neonatal streptozotocin-induced diabetic (n-STZ) rats. B. subtilis MORI produces 1-deoxynojirimycin (DNJ), an $\alpha$-glucosidase inhibitor. The content of DNJ of soybean fermented culture mixed with mulberry was higher (4.1$\pm$0.0 mg/g dry base) than that (1.5$\pm$0.0 mg/g) of mulberry. The concentration of 50% inhibition (IC50) against rat intestinal $\alpha$-glucosidase of soybean fermented culture mixed with mulberry was $5.6{\pm}0.1{\mu}g$/mL and that of mulberry was $17.0{\pm}0.5{\mu}g$/mL. Experimental groups of diabetic rats were randomly assigned to normal control group (NC group), diabetic control group (DC group) and three diabetic groups fed with DNJ food product. One of the three diabetic groups was M group (60 mg DNJ food product/kg) (DNJ food product containing 30% mulberry) and the other two were MM-60 group (60 mg/kg) and MM-120 group (120 mg/kg) (DNJ-fortified food product containing 30% fermented soybean culture mixed with mulberry leaves). The glucose in serum was significantly decreased in the MM-60 and MM-120 groups fed with DNJ-fortified food product for 4 weeks, compared with DC group. Total cholesterol and triglyceride in serum were also lower in MM-60 and MM-120 groups than the DC group. These results support that the fermented soybean culture of B. subtilis MORI mixed with mulberry leaves improved the metabolism of blood glucose and lipid in the n-STZ rat model.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.9
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• pp.1166-1171
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• 2006

This study was performed to investigate the effect of silk protein hydrolysates on blood glucose in diabetic mice (C57BL/KsJ db/db). The silk protein hydrolysates hydrolyzed by protease contains 87.52% of peptides of which molecular weight was below 2,000 dalton. The content of free amino acids was 14.80 g/100 g silk protein hydrolysates and major free amino acids were Pro, Thr, Arg and Ala. Silk protein hydrolysates were administered to the animals for 9 weeks at doses of 0.2, 0.5% and 0.8% solution. The body weight increase in the 0.5 and 0.8% fed groups were higher than control group. Food and water intake in the silk protein hydrolysates fed groups were lower than control group. The weight of liver was not different among groups, while the weight of kidney in control group was higher than silk protein hydrolysates fed groups. The blood glucose level in silk protein hydrolysates fed groups was lower than control group. In the glucose tolerance test, the blood glucose level in control group was the highest at 15 minutes after glucose injection while those in silk protein hydrolysates fed groups were the highest at 30 minutes. Results in this study suggest that silk protein hydrolysates show hypoglycemic effect in C57BL/KsJ db/db mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.321-326
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• 2011

The aim of the present study was to investigate antihyperglycemic effect of Gleditschiae Spina (GS) in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. The rats were divided into four groups: normal control (NC), diabetic control (DC), diabetic rats supplemented with acarbose (AC, 4 mg/kg), and with GS ethanol extracts (GSE, 50 mg/kg). Weekly fasting blood glucose (FBG) for 10 weeks and oral glucose tolerance test (OGTT) at 10th week were monitored using glucose oxidase-peroxidase reactive strips. The FBG level was significantly reduced in AC group after 8 weeks and in GSE group at the end of period. The AUCs for the glucose response from OGTT and blood glucose level after sacrifice were significantly lower in the AC and GSE groups than the DC group. GSE supplementation significantly increased plasma total radical-trapping antioxidant potential (TRAP) in STZ-NA-induced diabetic rats, compared with DC group. The present study indicates that GSE could ameliorate type 2 diabetes and be comparable to acarbose, a standard hypoglycemic drug. Also, we suggest that GSE may possess antioxidant activity against the STZ-NA-induced oxidative stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.10
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• pp.1611-1617
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• 2004

This study was carried out to examine the effects of pills made of mulberry leaves and silkworm powder on lowering blood glucose level. Experimental animals were Sprague-Dawley male rat weighing 100$\pm$10 g and pills were supplemented with 0.4% (4 g/kg) diet. Experimental groups were assigned to diabetic group (DM group) and pill supplemented groups. Pill supplemented groups were classified 100% mulberry leaves (M group), mixing 25% silkworm powder to mulberry leaves (25SM group), mixing 50% silkworm powder to mulberry leaves (50SM group), mixing 70% silkworm powder to mulberry leaves (75SM group) and 100% silkworm powder (100S group). Experimental diets and water fed ad libitum, and streptozotocin was injected to induce diabetic state after 3rd weeks and sacrificed on the 9th day. The contents of 1-deoxynojirimycin(DNJ) were increased with adding the silkworm powder. The contents of GABA and rutin were increased with adding the mulberry leaves. In vitro, intestinal mucosa $\alpha$-glucosidase inhibitory activities were significantly increased in pills which mixed with silkworm powder by 50%. Blood glucose levels were high in groups which mixed with silkworm powder by 50% compared to DM group. Intestinal mucosa maltase activity in proximal part was significantly reduced in pill supplemented group compared to DM group and pill supplemented groups were no significant difference. Enzyme activity in middle part was no significant difference in experimental groups. Enzyme activity in distal part was decreased in pill supplemented groups, especially in 50SM, 75SM and 100S groups were significantly reduced compared to DM group. Sucrase and lactase activities in pill supplemented groups were significantly reduced at proximal part, and there was no significant difference in middle and distal parts. In conclusion, pills made of mulberry leaves and silkworm powder increased the $\alpha$-glucosidase inhibitory activity in vitro and reduced the blood glucose levels by controlling the disaccharidase activities of intestinal proximal part in STZ-induced diabetic rat. The synergistic effect was the highest when mulberry leaves was mixed with silkworm powder by the ratio of 50 : 50.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.6
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• pp.759-765
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• 2012

This study was performed to investigate improvements in diabetes mellitus by extracts of yacon in streptozotocin (STZ)-induced diabetic rats. Fifty rats were divided into a normal group and four experimental groups. STZ (45 mg/kg) was injected intraperitoneally to induce type I diabetes in the four experimental groups. Yacon extracts were administered for 5 weeks. Forty-five ICR mice were also divided into one positive control group and four experimental groups for the oral glucose tolerance test (OGTT) after fed yacon extract. The control group did not eat any yacon extracts, while Group 1 (GI) was fed 125 mg/kg of yacon extracts, Group 2 (GII) was fed 250 mg/kg of yacon extracts, and Group 3 (GIII) was fed 500 mg/kg of yacon extracts. After treatment for 5 weeks, blood glucose in GIII group showed decreased tendency at the 5 week. In OGTT by glucose, the glucose level of yacon treatment group in diabetic rats was significantly decreased compared to the glucose level of the control group, but there was no difference in OGTT by maltose. In ICR mice, the glucose level of the experimental group in OGTT by maltose was significantly decreased compared to the control group. The area of the islets of Langerhans was increased by yacon treatment in a dose-dependent manner on diabetic rats. Insulin concentration of the GIII group was also decreased compared to the control group, while the concentration of fructosamine, total cholesterol, and triglycerides in serum showed no difference. OGTT by glucose or maltose in ICR mice or diabetic rats, area of the Islets of Langerhans, and insulin concentration improved. Yacon treatment may be a useful therapeutic and preventive strategy for diabetes mellitus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1071-1077
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• 2002

The purpose of this study was investigated the effects of YK-209 mulberry leaves on disaccharidase activites of small intestine and blood glucose-lowering in diabetic rats induced with streptozotocin (STZ). Male Sprague-Dawley rats weighing 100$\pm$10 g were randomly assigned to one normal and four STZ-induced diabetic groups; YK-209 0% mulberry leaves diet (DM group),0.1% YK-209 mulberry loaves diet (DM-0.1Y group),0.2% YK-209mulberry leaves diet (DM -0.2Y group), and 0.4% YK-209 mulberry leaves diet (DM -0.4Y group). Diabetes was induced by intravenous injection of 55 mg/kg body weight of STZ in sodium citrate buffer (pH 4.3) via tail vein after 3 weeks feeding of experimental diets. Rats were sacrificed at the 9th day of diabetic states. The functional ingredients in the mulberry leaves, the 1-deoxynojirimycin (DNJ) contents of YK-209 mulberry leaves was higher than those of the Cheongil mulberry leaves. ${\gamma}$ -Aminobutyric acid (GABA) and rutin contents of YK-209 mulberry leaves were 1.3 and 1.4 times higher than those of the Cheongil mulberry leaves, respectively, and vitamin C contents of YK-209 mulberry leaves were also higher than those of the Cheongil mulberry leaves. Intestine index was increased in all diabetic groups, compared with normal group but not significantly different among all diadetic groups. Level of blood glucose was decreased in diadetic rats by supplementation YK-209 mulberry leaves. The disaccharidase activities in proximal part of intestine such as maltase, sucrase, and lactase in YK-209 mulberry leaves supplementation groups were significantly lower than those of DM group, In conclusion, this research indicated that the functional ingredients of YK 209 mulberry leaves were higher than those of the Cheongil leaveses, and YK-209 mulberry leaves has the hypoglycemic effect in STZ-induced diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.8
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• pp.1086-1093
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• 2012

The hypoglycemic and hypolipidemic effects of autoclaved soy flour and DJI chungkukjang powder fermented using Bacillus subtilis DJI were investigated in type 2 diabetic animal models. After a 2-week adaptation period, the diabetic animal model db/db mice were divided into the diabetic control group (D-C group), a diabetic group fed with soybean (D-S group), and a diabetic group fed with DJI chungkukjang (D-CJ group). The body weight gain, food intake, water intake, liver, and adipose tissue weights were not significantly different between the experimental groups. The supplementation of DJI chungkukjang or autoclaved soy flour diet induced a marked reduction of fasting blood glucose, blood glycosylated hemoglobin levels, and glucose levels in the oral glucose tolerance test and AUC for glucose compared with the diabetic control group. However, DJI chungkukjang showed a much stronger antidiabetic effect than unfermented autoclaved soy flour. Serum insulin levels were the same among the groups. The supplementation of DJI chungkukjang or autoclaved soy flour diet also significantly lowered the serum triglyceride, total cholesterol, and LDL-cholesterol levels compared with the control diabetic group, while it elevated the HDL-cholesterol level in the serum. This data suggests that the dietary supplementation of autoclaved soy flour or DJI chungkukjang may be useful in the control of blood glucose in animals with type 2 diabetes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.3
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• pp.321-327
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• 2006

This study was performed to investigate the hypoglycemic effect of pine needle extract oil against type 2 diabetes. Six-week-old male C57BL/Ks(db/db) mice were divided into four groups : negative control, pine needle extract oil low dose, high dose and positive control groups, which fed daily for 6 weeks with corn oil, pine needle extract oil 112.5 mg/kg, 450 mg/kg or metformin (150 mg/kg ), respectively. The oral administration of the pine needle extract oil resulted in the significant and dose-dependent decreases of blood glucose levels in comparison with corn oil treatment. The levels of HbAlc showed a tendency of the decrease by the high dose treatment of the pine needle extract oil and were positively correlated with blood glucose levels (r=0.5046, p=0.0023) . However, the levels of serum insulin and C-peptide were not affected by pine needle extract oil or metformin treatments. The levels of serum leptin, which is related with the insulin sensitivity, showed a tendency of the increases by pine needle extract oil treatment and were negatively correlated to blood glucose levels (r=-0.4754, p=0.0052). In conclusion, these results suggest that the pine needle extract oil have a potential for the oral anti-hyperglycemic agent and the mode of action may be related with the improvement of the insulin sensitivity through blood leptin.

• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.83-88
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• 1984

It is now well established that the rodenticide Vacor (N-3-pyridyl-mehtyl-N'-p-nitropheny-lurea) causes a hyperglycemia in human and rats. It is also reported that there are some components (DPG-3) in ginseng radix which cause hypoglycemic effect on alloxan diabetic mice. In the present study, attempts were made to demonstrate in Vacor-poisoned rats the hypo-glycemic activity of red ginseng component(RGC), which was extracted by Kimura's DPG-3 extraction procedure and found to be effective for lowering a hyperglycemia in alloxan-diabetic rats. Vacor in a dose of $LD_{50}$ (10mg/kg) produced a glucose intolerance with a paradoxical moderate increase in blood immunoreactive insulin and derangement in glucose metabolism of epididymal adipocytes in rats. Although RGC (20mg/kg, i.p.) did not exert any significant influence on a hyperglycemia induced by large lethal doses (25mg/kg) of Vacor ingestion, it improved the LDso Vacor-induced glucose intolerance and caused a further increase in blood insulin levels in Vacor-poisoned rats. The administration of RGC (20mg/kg, i.p.) normalized Vacor-induced depression of glucose metabolism and lipogenesis in the epididymal adipocytes with an improvement of reduced responses to insulin of adipocytes from Vacor-poisoned rats. These results suggest that some red ginsneng components contained in RGC fraction normalize the depressed peripheral glucose unitlization and insulin response and eventually lead to an improvement of abnormal glucose tolerance developed in rats poisoned with small doses of Vacor.