• Toxicological Research
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• v.12 no.2
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• pp.213-221
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• 1996

In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.

• Food Science of Animal Resources
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• v.28 no.4
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• pp.445-450
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• 2008

The effects of fermented goat milk supplemented with citrus concentrate on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats were examined. Streptozotocin-nicotinamide-induced diabetic rats (type II) were divided into five experimental groups treated with metformin, goat milk, fermented goat milk, fermented goat milk containing citrus concentrate, or no supplementation (control). The rats in each group were examined weekly for blood levels of glucose, total cholesterol, triglyceride. HDL-cholesterol, LDL-cholesterol. and body weight. On the $24^{th}$ day of the experiment, an oral glucose tolerance test (OGTT) was carried out. Administration of fermented goat milk to the diabetic rats significantly decreased blood glucose and triglyceride levels, while administration of metformin (33.3 mg/kg body weight) did not significantly lower blood glucose levels. Fermented goat milk containing citrus concentrate caused a significant decrease in blood glucose levels in the OGTT at 30 min. This study shows that supplementation with fermented goat milk containing citrus concentrate may be a practical method of reducing blood glucose levels in type II diabetics.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.101-106
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• 2019

Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, $10^{-4}M$). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine $A_1$ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an ${\alpha}_1$-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular $Ca^{2+}$ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.619-628
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• 2023

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.903-909
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• 2017

This study was conducted to develop Helianthus tuberosus (HT) juice mixed with dried bitter melon juice and assess its hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. HT juice mixed with 5.0% dried bitter melon juice was used in this study. Male Sprague-Dawley rats were divided into four groups (eight rats per group) and drunk each sample for 4 weeks: normal water [normal control (NC) group], STZ+normal water (STZ group), STZ+HT juice (HT group), STZ+HT juice mixed with 2.5% bitter melon juice (HT2.5 group), and STZ+HT juice mixed with 5.0% bitter melon juice (HT5.0 group). HT juice was diluted to 25% in distilled water and supplied to rats. Food intake, body weight gain, and food efficiency ratio were lower in the STZ group than in the NC group. HT, HT2.5, and HT5.0 groups showed higher parameters than the STZ groups. Water intakes were higher in the STZ group than in the NC group. After 3 weeks, HT, HT2.5, and HT5.0 groups showed lower parameters than the STZ group. After 1 week, blood glucose level of the STZ group ($476.7{\pm}22.8mg/dL$) was significantly higher than those of the HT group ($376.3{\pm}25.8mg/dL$), HT2.5 group ($405.2{\pm}35.1mg/dL$), and HT5.0 group ($342.8{\pm}29.7mg/dL$). After 4 weeks, blood glucose level of the STZ group were significantly higher than those of the HT, HT2.5, and HT5.0 group. Serum insulin levels of the HT group ($3.13{\pm}0.32ng/mL$), HT2.5 group ($3.40{\pm}0.23ng/mL$), and HT5.0 group ($3.48{\pm}0.43ng/mL$) were higher than that of the STZ group ($2.72{\pm}0.53ng/mL$). These results indicate that H. tuberosus juice mixed with dried bitter melon juice helps prevent or attenuate progression of diabetes in rats with STZ-induced diabetes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.969-975
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• 1996

The purpose of this study was to investigate the effect of dietary vitamin E on microsomal mixed function oxidase system of liver and lung in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140 $\pm$ 10mg were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were divided into DM-0E(vitamin E free diet), DM-40E(40mg vitamin E kg/diet) and DM-400E(400mg vitamin E kg/diet) according to the level of vitamin E supplementation. Diabetes was experimentally induced by intravenous administration of 55mg/kg b.w of STZ in citrate buffer(pH 4.3) after 4 week feeding of three experimental diets. Animals were sacrificed at the 6th day of diabetic state. The contents of cytochrome P$_{450}$ in DM-0E, DM-40E and DM-400E groups of liver were increased by 162%, 150% and 56%, respectively, compared with that of control. Also the contents of cytochrome P$_{450}$ in lung were similar to liver. The activities of cytochrome bs in DM-0E and DM-40E groups of the liver were increased by 70% and 53%, respectively, compared with that of control, but not in DM-400E group. The activities of bs in DM-0E, DM-40E and DM-400E groups of lung were signficantly increased. Activity of cytochrome P$_{450}$ reductase in DM-0E, DM-40E of liver and lung were higher than that of control group, but the activity of DM-400E group was not different from that of control. The lipid peroxide values of DM-0E, DM-40E and DM-400E groups were 143%, 95% and 31% higher than those of control. It was concluded that dietary vitamin E had protective effects on lipid peroxidation accompanied with increased mixed function of oxidase activity in diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.510-518
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• 2012

This study examined the biological activity and synergistic effects of an extract of Wa-song ($Orostachys$ $japonicus$, OE), a medicinal plant mixture (MPE) and a combination of both at different ratios (1:1, OMPE-1 and 3:1, OMPE-3). Extracts of the medicinal plants mixture were comprised of Baekbokyung, Changchul and Sa-in at the same ratio. The antioxidant activity of the extracts and their complex were tested $in$ $vitro$. The $in$ $vivo$ antioxidant activity was also analyzed by examining the lipid composition in the liver and kidney of streptozotocin (STZ)-induced diabetes rats. The nitric oxide radical scavenging activity was more than 50% in OMPE-3 at a 1,000 ${\mu}g$/mL concentration. Regarding metal ions, such as $Fe^{2+}$ and $Cu^{2+}$, the antioxidant activity of OMPE-1 and OMPE-3 was higher than that of OE and MPE. OMPE-1 and 3 had higher activity on $Cu^{2+}$ ions than $Fe^{2+}$ ions. The ${\alpha}$-glucosidase inhibition activity of the OE extract was higher than that of MPE and OMPE-1 but the relative activity of OMPE-3 was significantly higher than the others. Freeze-dried MPE, OMPE-1 and OMPE-3 were added to the diet at a level of 1% given to STZ induced diabetes rats for 4 weeks. The OMPE-1 and OMPE-3 administered groups showed significant decreases in the total lipid, total cholesterol and triglyceride levels in the liver and kidney. In these groups, the glycogen accumulation level of the liver was increased significantly. The content of thiobarbituric acid reactive substances (TBARS) in the liver and kidney was decreased but the DPPH radical scavenging activity was increased. These results suggest that Wa-song extract exhibits antioxidant and antidiabetic activity, which are enhanced by a complex with a medical plants extract.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.5
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• pp.621-629
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• 2012

This study investigated the effect of soybeans, $chungkukjang$, and $doenjang$ on blood glucose and serum lipid profile in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing 205 g were divided into non-diabetic and diabetic groups. The diabetic groups were further subdivided into four experimental groups: a normal group (N), a diabetic control group (STZ-C), a diabetic group fed autoclaved soybean powder (STZ-S), a diabetic group fed $chungkukjang$ powder (STZ-CKJ) and a diabetic group fed $deonjang$ powder (STZ-DJ). Food and water intakes were higher in the diabetic groups than in the N group. The body weight gain and food efficiency ratios were higher in the STZ-S, STZ-CKJ, and STZ-DJ groups than in the STZ-C group, but created no significant changes between the diabetic groups on food intake and body weight gain. The whole blood level at 4 weeks of the STZ-CKJ group was significantly lower than the STZ-C group. Serum glucose levels of the STZ-S, STZ-CKJ, and STZ-DJ groups were significantly lower than the STZ-C group, but there was no significant change in serum insulin levels. The AST and ALP activities in serum were markedly higher in the STZ-C group, but these decreases in relation to diabetes increased in the STZ-S, STZ-CKJ, and STZ-DJ groups. The level of serum triglycerides was lower in the STZ-CKJ and STZ-DJ groups than in the STZ-C group, whereas level of serum HDL-cholesterol was higher in the STZ-CKJ and STZ-DJ groups. Levels of total serum and LDL-cholesterol were higher in the diabetic groups compared with the N group, but significantly decreased in the STZ-S, STZ-CKJ, and STZ-DJ groups compared to the STZ-C group. These results indicate that dietary supplements of soybean, $chungkukjang$ and $doenjang$ may improve blood glucose and lipid metabolism and help prevent or attenuate the progression of diabetes in STZ-induced diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.12
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• pp.1761-1768
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• 2010

Hypoglycemic effect through activity inhibition of $\alpha$-glucosidase and $\alpha$-amylase was evaluated using leaves of Eleutherococcus senticosu, Eleutherococcus gracilistylus, Eleutherococcus sieboldianus and Eleutherococcus sessiliflorus which belong to Acanthopanax sessiliflorus genus. As a result of measuring $\alpha$-glucosidase activity inhibition, extract of Eleutherococcus gracilistylus showed around 43.38% of activity inhibition compared with acarbose and extract of Eleutherococcus senticosu showed 41.24% inhibitory effect. As a result of measuring $\alpha$-amylase activity inhibition, acarbose showed 73.25% of activity inhibition in 10 mg/mL concentration, and the extract of Eleutherococcus senticosu leaves showed 91.90% higher activity inhibition compared with acarbose. Also, after subjects in a model were induced diabetes with streptozotocin (STZ) intake plant extract from Acanthopanax sessiliflorus for 2 weeks, effect of improving blood glucose level and fat was examined. In all groups with specimen, Eleutherococcus senticosu (T1), Eleutherococcus gracilistylus (T2), Eleutherococcus sieboldianus (T3) and Eleutherococcus sessiliflorus (T4), blood glucose level was significantly decreased compared with that in control group (C). In an experiment of examining changes in fat concentration in blood, total cholesterol content increased in a control group compared with a normal, while in T1, T3 and T4, it decreased significantly compared with the control group. As for HDL-cholesterol, it significantly increased in all diabetes induced groups compared with the normal group, and in T3, it increased the most significantly by 55.61% compared with the control group. In case of LDL-cholesterol, specific difference between the normal group and the control group was not found; however, significant increase was detected in T2 and T3, whereas in T1 and T4, it decreased significantly compared with the control group. As for triglyceride, its concentration increased in the control group like total cholesterol. It decreased 60.16% in T3, 60.80% in T4 and 50.16% in T1 compared with the control group. As a result of measuring the concentration of triglyceride in extracted liver, the control group showed significant increase compared with the normal group, whereas T1 and T2 showed significant decrease compared with the normal group. The above results show that extracts from Acanthopanax sessiliflorus genus are effective for hypoglycemic and improving fat metabolism due to diabetes.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.196-204
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• 2009

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.