• Archives of Pharmacal Research
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• v.25 no.6
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• pp.917-922
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• 2002

We investigated the long term effects of Sopungsungi-won (SP), a Korean traditional formula used for senile constipation and diabetes mellitus, on the development of diabetic nephropathy (DN) in Zucker diabetic fatty (ZDF) rats. ZDF rats were fed regular laboratory chow mixed with SP or rosiglitazone (RSG) for an 8-week period. Kidney hypertrophy was developed with increasing plasma glucose level, and glomerular hypertrophy was improved by 22% and 45% in SP- and RSG-treated rats, respectively. Urinary glucose and albumin excretions were also significantly lower in SP-treated rats than in ZDF control rats. Activation of the mitogen-activated protein kinase (MAPK)-transforming growth factor ${\beta}1$ (TGF ${\beta}1$)-fibronectin pathway in kidney, responsible for glomerular dysfunction, was markedly blunted by SP treatment in a dose dependent manner. Our findings, for the first time, provide strong evidence that long-term administration of SP formula prevents the development and progression of DN in ZDF rats. Human trials are needed to confirm these experimental results.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.1-14
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• 2014

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

• Journal of Korean Academic Society of Home Health Care Nursing
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• v.23 no.2
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• pp.139-146
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• 2016

Purpose: This research seeks to identify differences between general characteristics, disease-related characteristics, glycated hemoglobin (HbAlc) levels, and aspects of chronic complications of diabetes mellitus in type 2 diabetes. Methods: This research was conducted from the 1st to the 15th of February in 2016, on 263 in patients. Patients' electronic medical records were used to identify their general characteristics, disease-related characteristics, HbAlc, and chronic diabetic complications. Chi-square test, ANOVA, ANCOVA, and the Cochran-Mantel-Haenszel test were used for data analysis. Results: Statistical significance was observed for general characteristics, based on smoking status, such as age, and education level; disease-related characteristics differed according to the duration of diabetes. Smoking status did not differ according to HbAlc level. In term of chronic diabetic complications, statistically significance was observed for diabetic nephropathy, based on smoking status. Conclusion: Patients who had a history of smoking, but were not currently smoking, were likely to display higher HbAlc levels and diabetic nephropathy. Therefore, there is need for regular checkups for diabetic complications among patients with a history of smoking and it is important to emphasize smoking cessation.

• Bulletin of Food Technology
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• v.24 no.1
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• pp.53-61
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• 2011

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.2005-2017
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• 2007

Diabetic nephropathy remains a major cause of morbidity and mortality in the diabetic population and is the leading cause of end-stage renal failure. Despite current therapeutics including intensified glycemic control and blood pressure lowering agents, renal disease continues to progress relentlessly in diabetic patients, albeit at a lower rate. Since synthetic drugs for diabetes are known to have side effects, fungal mushrooms as a natural product come into preventing the development of diabetes. Our previous report showed the hypoglycemic effect of extracellular fungal polysaccharides (EPS) in streptozotocin (STZ)-induced diabetic rats. In this study, we analyzed the differential expression patterns of rat kidney proteins from normal, STZ-induced diabetic, and EPS-treated diabetic rats, to discover diabetes-associated proteins in rat kidney. The results of proteomic analysis revealed that up to 500 protein spots were visualized, of which 291 spots were differentially expressed in the three experimental groups. Eventually, 51 spots were statistically significant and were identified by peptide mass fingerprinting. Among the differentially expressed renal proteins, 10 were increased and 16 were decreased significantly in diabetic rat kidney. The levels of different proteins, altered after diabetes induction, were returned to approximately those of the healthy rats by EPS treatment. A histopathological examination showed that EPS administration restored the impaired kidney to almost normal architecture. The study of protein expression in the normal and diabetic kidney tissues enabled us to find several diabetic nephropathy-specific proteins, such as phospholipids scramblase 3 and tropomyosin 3, which have not been mentioned yet in connection with diabetes.

• Korean Journal of Pharmacognosy
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• v.47 no.4
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• pp.312-318
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• 2016

Advanced glycation end products (AGEs) such as $N^{\varepsilon}$-(carboxy-methyl)lysine (CML) have been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the inhibitory effects of ethanolic extract of Aster koraiensis (AKE) on AGEs formation and AGEs-collagen cross-linking in vitro and CMLs formation in streptozotocin (STZ)-induced diabetic rats. AKE significantly inhibited AGEs formation ($IC_{50}$ value of $18.74{\mu}g/mL$) and AGEs-collagen cross-linking ($IC_{50}$ value of 0.274 mg/mL) in vitro than the well-known glycation inhibitor aminoguanidine ($IC_{50}$ value of $72.12{\mu}g/mL$ and 1.99 mg/mL, respectively). AKE (100 mg/kg per day) was given to diabetic rats for 9 weeks. In STZ-induced diabetic rats, severe hyperglycemia was developed, and urinary CMLs and plasma CMLs were markedly increased. Immunohistochemical stain revealed that CMLs were accumulated within renal glomerulus in STZ-induced diabetic rats. However, AKE significantly reduced urinary CMLs and plasma CMLs in diabetic rats. CMLs accumulation was inhibited by AKE treatment in the renal glomerulus. These results suggest that AKE had an inhibitory effect of AGE accumulation in the glomeruli of diabetic rat and could be an inhibitor of AGE-induced protein cross-linking. The oral administration of AKE may significantly help to prevent the progression of diabetic nephropathy in patients with diabetes.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.137-152
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• 1998

Acute complications of diabetes mellitus were diminished after Banting and Best discovered insulin. But chronic complications of diabetes mellitus have been increased. The main complications of diabetes mellitus are diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic foot lesion and macrovascular complication. These complications can result in renal failure, loss of sight, cerebral infarction and myocardial infarction. So it is very difficult to treat the complications of diabetes mellitus. In oriental medicine, the transformations(傳變症) of Sogal(消渴) are edema, carbuncle, loss of sight and so on. The comparative study between the trcmsformations(傳變症) of SogaI(消渴) and the complications of diabetes mellitus has come to the following conclusions. 1. In oriental medicine, diabetic retinopathy was expessed as loss of sight and the treament of diabetic retinopathy should be started at an early stage, to prevent vitreous hemorrhage and traction retinal detachment. 2. In oriental medicine. diabetic nephropathy was expressed as edema and the treatment should be started at an early stage of renal injury when the protein comes from urine.3. Symmetrical distal polyneuropathy is the main part of diabetic neuropathy and it was expressed as weakness of the lower limbs and pain of joints in the symptoms of Haso(下消). In Oriental medicine, acupuncture and herb medicine which effect is SopungHwalHyul can treat polyneuropathy. 4. Chief macrovascular complications are coronary artery disease and cerebrovascular disease, The cause of macrovascular complication is atherosclerosis. So the method of treating atherosclerosis should be studied in oriental medicine. 5. Diabetic foot were expressed as carbuncle and its main causes are decreasing perfusion of fool, diabetic neuropathy and infection. So these causes should be studied in oriental medicine. 6. The complications of diabetes mellitus afe very similar to the transfonnatiuns of Sogal(消渴).The control of blood glucose is indispensable to prevent and delay the complication of diabetes mellitus.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.367-386
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• 2012

Objectives : The object of this study was to observe the effects of Gamioryung-san (GOS), which consists of 22 types of herbs, on streptozotocin (STZ)-induced diabetic nephropathy rats. Methods : Three different dosages of GOS were orally administered once a day for 28 days from 3 weeks after STZ treatment. Six groups, each of 8 rats per group were used. Changes on the body weights, blood glucose levels, serum BUN and creatinine levels, urine volumes, and UAER were observed with changes on the kidney malondialdehyde contents and glutathione, dismutase and catalase contents. In addition, histopathology of kidney, pancreas, thymus and spleen were observed. The results were compared with antioxidant silymarin 100 mg/kg, of which the effects on STZ -induced diabetes and related complications are already confirmed. Results : As a result of treatment of GOS 800, 400 or 200 mg/kg for 28 days, STZ-induced decreases of body weights, hyperglycemia, atrophic changes of pancreatic islets with decreases of insulin-immunoreactive cells and decreases of glucagon -immunoreactive cells were inhibited dose-dependently. Increases in kidney weight, serum BUN and creatinine levels, urine volumes, UAER, vasodilated atrophic glomerulus and abnormal tubules were inhibited dose-dependently. Also increases of kidney MDA contents and decreases of GSH contents, SOD and CAT activities, decreases of thymus and spleen weights, and atrophic changes at histopathological observation were also inhibited. The effects of GOS 400 mg/kg showed similar effects to silymarin 100 mg/kg. Conclusions : These results suggest that 400 mg/kg of GOS retarded the STZ-induced diabetic nephropathies as similarly to silymarin 100 mg/kg, through modulations of oxidative stress and immune systems.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.45-53
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• 1997

In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and $AT_1$ subtypes ($AT_{1A}$ and $AT_{1B}$) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and $AT_{1A}$ mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. $AT_1$B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.187-193
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• 2013

The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-${\alpha}$ and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.