• Preventive Nutrition and Food Science
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• v.16 no.3
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• pp.272-277
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• 2011

The hypoglycemic effects of germinated rough rice extract in streptozotocin (STZ)-induced diabetic rats were investigated. Weight gain was significantly lower in the diabetic groups than in the normal control (NC); however, they were higher in the 1% and 3% diabetic groups given germinated Goami2 rough rice extract (DM-3%GGRRE) than in the diabetic control (DC). While food intake in all diabetic groups was significantly higher than that of the NC, there was no significant difference among all diabetic groups. The weight percentages of liver and kidney in all diabetic groups were significantly higher than that of the NC. In terms of blood glucose, the diabetic group showed about a three times larger value than the normal group. Moreover, in the 3% germinated rough rice extract group, the blood glucose level became lowered. The levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine phosphokinsae, and creatinine increased in general with the induction of diabetes using STZ; however, the 3% GGRRE-treated group displayed a significant decrease in these levels compared to the diabetic group. The results show that the 3% GGRRE, rather than the 1% GGRRE, was considerably more effective at reducing blood glucose and improving impaired glucose tolerance, suggesting the germinated rice extracts may play a role in preventing liver and kidney damage.

• Journal of the East Asian Society of Dietary Life
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• v.15 no.2
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• pp.158-164
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• 2005

The present study was undertaken to evaluate the effect of Rhodiola sachalinensis root ethanol extract (RS), on the body weight, organ weight, plasma glucose and plasma lipid in diabetic rats caused by streptozotocin (STZ). The body weight decreased more slowly in the RS group than in the diabetic, and the food intake increased significantly in all diabetic groups. The food efficiency was very low in all diabetic groups, but increased significantly in the RS groups than diabetic control (p<0.05). In comparing the weight of organ, the weight of liver and kidney were increased in all diabetic groups than in the control, and decreased slightly in RS groups. The weight of heart and spleen were not different among all test groups. The glucose in serum was decreased significantly in the RS groups fed the RS for 4 weeks, compared to the diabetic control (p<0.05). Total cholesterol, triglyceride and atherogenic index (AI) in serum were significantly higher in diabetic control, compared to the normal (p<0.05), and decreased $16.7\%,\;18.3\%\;and\;45.0\%$, respectively, in the RS fed $300\;\cal{mg/kg}$ of RS. HDL-cholesterol was increased slightly more in the $RS-300\;\cal{mg/kg}$, compared to diabetic control. These findings suggest that RS treatment has protective effect in diabetes.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.808-812
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• 2009

The ${\alpha}-glucosidase$ inhibitory and antioxidant effects of water chestnut (Trapa japonica Flerov.) were assessed to explore its possible use as an anti-diabetic agent. Methanol extracts of the fruit shell and meat of water chestnut were assayed for inhibitory activity against yeast ${\alpha}-glucosidase$ and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Effect of fruit shell extract on postprandial glucose response was assessed. Compared with fruit meat, shell extract showed stronger inhibition against ${\alpha}-glucosidase$ with an $IC_{50}$ of 273 ${\mu}g/mL$. Oral administration of fruit shell extract (500 mg/kg) significantly lowered the postprandial area under the glucose response curve to starch (1 g/kg) in streptozotocin (STZ)-induced diabetic rats (p<0.01). Compared with fruit meat, shell extract showed stronger scavenging activity against DPPH, with an $IC_{50}$ of 27.1 ${\mu}g/mL$. The results indicate that the fruit shell of water chestnut was effective in controlling postprandial hyperglycemia and exerted an antioxidant effect. Therefore, water chestnut may be useful in treating diabetes.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.341-354
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• 2021

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

• Journal of the Korean Applied Science and Technology
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• v.36 no.3
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• pp.898-904
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• 2019

This study was carried to investigate the antidiabetic effect of ethanol extract of Astragali Radix(A.R) in Streptozotocin(STZ) induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose of 45mg/kg dissolved in citrate buffer. The ethanol extract of A. R was orally administrated once a day for 7 days at a dose of 1,000mg/kg. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in A.R treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucokinase(GK) and glucose-6-phosphate dehydrogenase(G-6-PDH) were significantly increased, and activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in A.R treated group compared to the those of STZ-control group, These results indicated that ethanol extract of A.R would have antidiabetic effect in STZ-induced diabetic rats.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.826-833
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• 2002

This study was conducted to investigate the effects of YK-209 mulberry leaves on HMG-CoA reductase activity and lipid composition of liver in streptozotocin-induced diabetic rats. Sprague-Dawley male rats weighing 100 $\pm$ 10 B were randomly assigned as a normal group and four STZ-induced diabetic groups according to the level of dietary mulberry leaves supplement. The experimental diets were fed ad libidum, so that diabetes was experimentally induced by intravenous injection of STZ 55 mg/kg of body weight after feeding for 3 weeks. Animals were sacrificed on the 9th day of diabetic states. The levels of serum triglyceride, total-cholesterol and LDL-cholesterol in DM group were higher than mulberry leaves supplemented groups and normal group, but those of the mulberry leaves supplemented groups were significantly decreased to normal level. In contrast, the leavels of serum HDL-cholesterol in DM group was significantly reduced than that of normal group, but mulberry leaves supplemented groups were increased to normal level. Atherogenic index in DM group was higher about 3 fold than the normal group but the DM-0.1Y and DM-0.2Y groups were maintained the normal level. Contents of total lipid and triglyceride of liver in DM group were significantly lower than that of normal group, but the mulberry Leaves supplemented groups increased than that of DM group. The contents of hepatic cholesterol in DM group was 160% higher than that of normal group, but the mulberry leaves supplementation groups maintained the normal level. The activity of hepatic 3-hydroxy -3-methylglutaryl Coenzyme A (HMG-CoA) reductase in DM group was 43% lower than that of normal group, but had no significant difference between DM-0.1Y, DM-0.2Y and normal groups. In conclusion, YK-209 mulberry loaves has improving effect of the lipid metabolism in STZ-induced diabetic rats through hepatic HMG-CoA reductase activity, and the change of lipids contents in serum and liver.