• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.155-170
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• 2006

Objectives : This study aimed to evaluate the hypoglycemic, hepatoprotective, and nephroprotective effects of 'Saengjinyanghyul-tang($Sh\={e}ngj\={i}ny\v{a}ngxu\`{e}-t\={a}ng$ : SJYHT)' in streptozotocin (STZ)-induced diabetic SD rat model. Methods : SJYHT extracts were once a day dosed for 28 days at a dosage 1000, 500, and 250mg/kg/5ml from 25 days after STZ-dosing, and the changes on blood glucose levels, liver and kidney weight, serum AST, ALT, BUN and creatinine levels were observed with histological changes on the liver and kidney. Results : Increased blood glucose levels, and diabetic hepatopathy & nephropathy including increased serum AST, ALT, BUN and creatinine levels, histological changes after STZ-dosing were dose-dependently reduced by SJYHT extract-dosing. Conclusions : 'SJYHT' water extracts have favorable hypoglycemic, hepatoprotective, and nephroprotective effects on the STZ-induced diabetic SD rats. Therefore, it is expected that 'SJYHT' has potential for use in the management of diabetes and diabetic complications.

• Biomedical Science Letters
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• v.12 no.3
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• pp.217-224
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• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.25-33
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• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Kidney Research and Clinical Practice
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• v.35 no.2
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.383.2-383.2
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• 2002

Diabetic nephropathy is major chronic complication of diabetes mellitus. Advanced glycation endproducts(AGEs) are largely involved in the pathogenesis of diabetic nephropathy. The irreversibly formed AGEs do not return to normal even if hyperglycemia is corrected and continue to accumulate over the lifetime of protein. The AGEs inhibitor. aminoguanidine(AG), is the only protein glycation inhibitor currently under development. its safety however is desirable. To find possible AGEs inhibitor in herbal medicines, bovine serum albumin was added to a mixture of sugars and some of processed. unprocessed herbal medicines or AG. Cyperi rhizoma was processed in four different methods according to chinese pharmacopoeia and traditional literatures. In comparision to the negative control with no inhibitor and positive control with AG. alcoholic extracts of these processed cyperi rhizoma proved to have more potent inhibitory activities than that of unprocessed cyperi rhizoma. These results revealed that some processed herbal medicines have a more potent in vitro inhibitory action on AGEs formation than AG. suggesting the possible candidate for diabetic nephropathy from the processed herbal medicines.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.912-919
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• 2001

The increased oxidative stress may play an important role on the pathogenesis of diabetes and diabetic complications, and the blood level of vitamin C and lipid peroxidation in NIDDM patients may be used as an indicator for oxidative stress. However there is only scanty evidence on the blood level of vitamin C in NIDDM patients with or without diabetic complications. The study population consisted of 90 NIDDM patients(diabetes without complication, 48, and diabetes with complications, 42) and 41 normal subjects. The 42 diabetic complications were divided into 3 groups : 15 diabetic nephropathy, 18 diabetic neuropathy, 9 diabetic retinopathy. The anthropometric data and blood biochemical data were studied. The dietary intake was determined by 24 hour recall methods and food frequency questionnaire. The plasma concentrations of MDA and vitamin C were determined by fluorophotometer and HPLC respectively. 1) In blood lipoprotein study, diabetes with complication had higher level of TG than diabetes without complications, while no significant differences in total cholesterol, HDL, and LDL were shown. Diabetic neuropathy had the highest TG level among diabetic complication groups. 2) The intakes of vitamin B complexes(vitamin B$_2$, vitamin B$_{6}$, not vitamin B$_1$) and antioxidant vitamins(vitamin A and vitamin E, not vitamin C) and certain minerals such as iron and calcium in diabetes were not sufficient but the intakes of energy, protein, niacin, and phosphorus in diabetes were sufficient. The dietary intakes between diabetes with-and without complications were not significantly different. Among diabetic complications, the diabetic retinopathy had the lowest intake of vitamin B$_2$ and B$_{6}$(p < 0.05). the diabetic neuropathy or nephropathy consumed extremely low amount of vitamin A. 3) The MDA concentrations of NIDDM was significantly higher than that in controls(p < 0. 05) while no significant difference in the MDA concentration between with and without complications was shown. Although there were no statistical differences, the diabetic nephropathy and diabetic neuropathy showed the higher concentration of MDA than the diabetes without complications or diabetic retinopathy. 4) The plasma concentration of vitamin C in controls was higher than that in diabetes(p < 0.05) while the plasma vitamin C in diabetes with and without complications were similar. In diabetic complications, no differences in plasma vitamin C concentration of three groups were shown. This study showed that the oxidative stress in NIDDM patients was highly increased and the vitamin C reserve was significantly depleted, as compared with normals, although their intakes of vitamin C met korean RDA, which means that diabetes need more vitamin C intake to decrease oxidative stress in NIDDM patients.nts.

• Childhood Kidney Diseases
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• v.9 no.1
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• pp.97-101
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• 2005

Renal diseases other than diabetic nephropathy can occur In diabetic patients. Urinary abnormalities or clinical courses inconsistent with the natural progression of diabetic nephropathy are suggestive of non-diabetic renal diseases and should lead to more extensive investigations. Presence of non-diabetic renal diseases in diabetic patients can alter the treatment plan and the prognosis. We report a 9-year-old girl who had type 1 membranoproliferatiye glomerulonephritis as well as type 1 diabetes mellitus.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.379-388
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• 2013

Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat-processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat-processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat-processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy.

• 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.