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Background: GS-E3D is a newly developed pectin lyase-modified red ginseng extract. The purpose of this study was to investigate the therapeutic effects of GS-E3D on diabetes-related renal dysfunction in streptozotocin-induced diabetic rats., Method: GS-E3D (25, 50, and 100 mg/kg body weight per day) was administered for 6 weeks. The levels of blood glucose and hemoglobin A1c, and of urinary albumin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and advanced glycation end-products (AGEs) were determined. Kidney histopathology, renal accumulation of AGEs, and expression of α-smooth muscle actin (α-SMA) were also examined., Results: Administration of GS-E3D for 6 weeks reduced urinary levels of albumin, 8-OHdG, and AGEs in diabetic rats. Mesangial expansion, renal accumulation of AGEs, and enhanced α-SMA expression were significantly inhibited by GS-E3D treatment. Oral administration of GS-E3D dose-dependently improved all symptoms of diabetic nephropathy by inhibiting renal accumulation of AGEs and oxidative stress., Conclusion: The results of this study indicate that the use of GS-E3D as a food supplement may provide effective treatment of diabetes-induced renal dysfunction.

High-mobility group box-1 (HMGB1) is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE) on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day) was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE) and the activity of nuclear factor-kappa B (NF-κB) in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.

The retinal accumulation of advanced glycation end products (AGEs) is a condition, which is found in diabetic retinopathy. The purpose of the present study was to investigate the protective effect of Litsea japonica extract (LJE) and to elucidate its underlying protective mechanism in model diabetic db/db mice. Male, 7 -week-old db/db mice were treated with LJE (100 or 250 mg/kg body weight) once a day orally for 12 weeks. The expression levels of AGEs and their receptor (RAGE) were subsequently assessed by immunohistochemistry. An electrophoretic mobility shift assay and southwestern histochemistry were used to detect activated nuclear factor κB (NF-κB). The immunohistochemical analysis demonstrated that LJE significantly reduced the expression levels of the AGEs and RAGE in the neural retinas of the db/db mice. LJE markedly inhibited the apoptosis of retinal ganglion cells. In addition, LJE suppressed the activation of NF-κB. These results suggested that LJE may be beneficial for the treatment of diabetes-induced retinal neurodegeneration, and the ability of LJE to attenuate retinal ganglion cell loss may be mediated by inhibition of the accumulation of AGEs.

Many dietary supplements have been sold through advertising their large number of beneficial effects. The aim of this study was to determine whether bilberries (Vaccinium myrtillus) help to prevent diabetes-induced retinal vascular dysfunction in vivo. V. myrtillus extract (VME; 100 mg/kg) was orally administered to streptozotocin-induced diabetic rats for 6 weeks. All diabetic rats exhibited hyperglycemia, and VME did not affect the blood glucose levels and body weight during the experiments. In the fluorescein-dextran angiography, the fluorescein leakage was significantly reduced in diabetic rats treated with VME. VME treatment also decreased markers of diabetic retinopathy, such as retinal vascular endothelial growth factor (VEGF) expression and degradation of zonula occludens-1, occludin and claudin-5 in diabetic rats. In conclusion, VME may prevent or delay the onset of early diabetic retinopathy. These findings have important implications for prevention of diabetic retinopathy using a dietary bilberry supplement.

Background: Platelet-derived growth factor-BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats., Methods: PCE (100, 350 mg/kg/day) was administered to diabetic rats for 16 weeks. Blood glucose and albuminuria were measured. Renal histology, α-smooth muscle actin (α-SMA), and proliferating cell nuclear antigen (PCNA) expression levels were also examined., Results: After 16 weeks of treatment with PCE, severe hyperglycemia and albuminuria were observed in the diabetic rats. The expressions levels of α-SMA and PCNA proteins were significantly increased in the glomeruli of the diabetic rats. The expression levels of PDGF-BB and its receptor expressions were greatly increased in the glomeruli of the diabetic rats. However, PCE markedly reduced albuminuria in the diabetic rats. PCE inhibited α-SMA and PCNA up-regulation and ameliorated PDGF-BB and PEGFR-ß protein expression in the diabetic rats. In addition, the binding of PDGF-BB/PDGFR-ß was inhibited by PCE as shown by an in vitro assay., Conclusions: These results suggest that PCE has an inhibitory effect on mesangial proliferation in diabetic renal tissues via the inhibition of the interaction of PDGF-BB with its receptor. PCE may have beneficial effects in preventing the progression of diabetic nephropathy.

Chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs), which accelerates the development of diabetic complications. Previous studies have shown that extract of Cassiae semen (CS), the seed of Cassia tora, has inhibitory activity on AGEs formation in vitro and reduces transforming growth factor-beta1 (TGF-β1) and extracellular matrix protein expression via inhibition of AGEs-mediated signaling in glomerular mesangial cells. In this study, to examine the preventive effects of CS extract on the development of diabetic nephropathy in vivo, streptozotocin (STZ)-injected diabetic rats were orally administered CS extract (200 mg/kg body weight/day) for 12 weeks. Serum glucose, triglycerides, and total cholesterol in diabetic rats were significantly higher compared to control rats. CS or aminoguanidine (AG) treatment significantly reduced these factors. Proteinuria and creatinine clearance were also significantly decreased in the CS-treated group compared with the untreated diabetic group. The CS-treated group had significantly inhibited COX-2 mRNA and protein, which mediates the symptoms of inflammation in the renal cortex of diabetic rats. Furthermore, histopathological studies of kidney tissue showed that in diabetic rats, AGEs, the receptor for AGEs, TGF-β1, and collagen IV were suppressed by CS treatment. Our data suggest that oral treatment of CS can inhibit the development of diabetic nephropathy via inhibition of AGEs accumulation in STZ-induced diabetic rats., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Objectives: KIOM-79, a combination of four plant extracts, has a preventive effect on diabetic nephropathy and retinopathy in diabetic animal models. In this study, we have investigated the inhibitory effects of KIOM-79 on diabetic cataractogenesis., Methods: We evaluated aldose reductase activity during cataractogenesis using Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. ZDF rats were treated orally with KIOM-79 (50 mg/kg body weight) once a day for 13 weeks., Key Findings: In vehicle-treated ZDF rats, lens opacity was increased, and lens fibre swelling and membrane rupture were observed. In addition, aldose reductase activity and aldose reductase protein expression in diabetic lens were markedly enhanced. However, the administration of KIOM-79 inhibited the development of diabetic cataract through the inhibition of aldose reductase activity and protein expression in diabetic lenses., Conclusions: These observations suggested that KIOM-79 was useful against the treatment of diabetic cataractogenesis., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Background: The purpose of the experiment reported here was to assess the involvement of advanced glycation end products (AGEs), oxidative stress, and nuclear factor kappa-B (NF-κB) activation in the development of diabetic keratopathy., Methods: Diabetes was induced by intraperitoneal streptozotocin injection in male Sprague-Dawley rats. The thickness of the cornea was measured. Apoptosis was detected by TUNEL assay and western blot for caspase-3. The expression of AGEs and 8-hydroxydeoxyguanosine (8-OHdG) were studied by immunohistochemistry in corneal tissues of normoglycaemic and diabetic rats. NF-κB activation was evaluated by electrophoretic mobility shift assay and southwestern histochemistry., Results: Corneal edema was observed in diabetic rats. The thickness of cornea was higher in diabetic than in control rats. AGEs were accumulated in corneal tissues. 8-OHdG and NF-κB were identified in corneal epithelium, stroma and endothelium, and its expressions were greater in diabetic than in those of control rats. Diabetes induces significant alterations in rat corneal tissue structure., Conclusions: The higher expression of AGE, 8-OHdG and NF-κB in corneal tissues of diabetic rats suggests that these factors are involved in apoptosis and in subsequent corneal alterations related to diabetic keratopathy.

Advanced glycation end products including Nε-(carboxymethyl)lysine (CML) are believed to contribute to retinal pericyte loss in diabetic retinopathy. Nuclear factor-κB (NF-κB) activation has been considered as a potential cytotoxic modulator of retinal pericytes. Herein, we investigated whether CML accumulation can trigger NF-κB activation and apoptosis of retinal pericytes in streptozotocin (STZ)-induced diabetic rats. Seven-week-old Sprague-Dawley rats were made diabetic (STZ, 60 mg/kg). After 5 months, CML level and NF-κB activation were measured in trypsin-digested retinal vessels. In diabetic rats, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive and caspase 3-positive retinal pericytes were significantly increased. CML and NF-κB activation was also markedly increased in diabetic retinal vessels. Moreover, the immunoreactivity of NF-κB was localized within the region where CML were accumulated. Apoptosis occurred in CML-accumulating retinal pericytes. These results suggest that NF-κB could be activated in CML-accumulating pericytes from diabetic retina. CML accumulation is responsible, at least in part, for the apoptosis of retinal pericytes., (Copyright © 2011 S. Karger AG, Basel.)

Advanced glycation end products (AGEs) is produced from glycolysis in vivo, which may result in diabetic nephropathy. Podocyte loss has been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the protective effects of Aster koraiensis extract (AKE), on the damage of renal podocytes in streptozotocin (STZ)-induced diabetic rats. AKE (100, 200mg/kg per day) was given to diabetic rats for 13weeks. Blood glucose, glycated haemoglobin (HbA1c), proteinuria and albuminuria were examined. Kidney histopathology, AGEs accumulation, apoptosis, and expression of Bax and Bcl-2 also were examined. In 20-week-old STZ-induced diabetic rats, severe hyperglycemia was developed, and proteinuria and albuminuria were markedly increased. TUNEL-positive signals were highly detected in glomeruli of STZ-induced diabetic rats. However, AKE reduced proteinuria and albuminuria in diabetic rats. AKE prevented AGEs deposition and podocyte apoptosis. Expression of Bax and Bcl-2 protein were restored by AKE treatment in the renal cortex. These results suggested that AKE has an inhibitory effect of AGE accumulation and anti-apoptotic effect in the glomeruli of diabetic rat. AKE could be beneficial in preventing the progression of diabetic nephropathy., (Copyright 2009 Elsevier Inc. All rights reserved.)

We investigated the effect of KIOM-79, 80% ethanolic extract of a new herbal prescription, on non-obese type 2 diabetic Goto-Kakizaki (GK) rats. The rats were treated orally with KIOM-79 (500 mg/kg body weight) once a day for 13 weeks to examine the long-term effects on hyperglycemia and glomerular histology as well as biochemical and functional abnormalities in kidney. As the results, we found that KIOM-79 reduced hyperglycemia (p<0.01), ameliorated insulin resistance (p<0.001), urinary protein excretion (p<0.01) and creatinine clearance (Ccr) (p<0.001), and inhibited glomerular AGE formation (p<0.001) in diabetic GK rats. We also found that KIOM-79 prevented the glomeruli enlargement, overexpression of type IV collagen (p<0.001), PKC protein (p<0.01), TGF-beta mRNA (p<0.05) and VEGF mRNA (p<0.05). Thus, based on our finding, KIOM-79 could reduce the hyperglycemia, and prevent or retard the development of diabetic nephropathy.

We investigated the effect of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl), a marker compound isolated from the cortex of Magnolia officinalis, in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. The rats were treated orally with magnolol (100 mg/kg body weight) once a day for 13 weeks. In magnolol-treated GK rats, fasting blood glucose and plasma insulin were significantly decreased, and the pancreatic islets also showed strong insulin antigen positivity. Urinary protein and creatinine clearance (Ccr) were significantly decreased. Pathological examination revealed the prevention of the glomeruli enlargement in magnolol-treated GK rats. The overproduction of renal sorbitol, advanced glycation endproducts (AGEs), type IV collagen, and TGF-beta1 mRNA were significantly reduced in magnolol-treated GK rats. Thus based on our findings, the use of magnolol could result in good blood glucose control and prevent or retard development of diabetic complications such as diabetic nephropathy.