• Archives of Plastic Surgery
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• v.41 no.5
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• pp.466-471
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• 2014

Background Bleeding can be a problem in wound debridement. In search for an effective hemostatic agent, we experimented with a chitosan film combined with the recombinant human epidermal growth factor (rh-EGF), hypothesizing that it would achieve effective hemostasis and simultaneously enhance arterial healing. Methods Forty-eight Sprague-Dawley rats were used, and 96 puncture wounds were made. The wounds were divided into the following four groups: treated with sterile gauze, treated with gelatin sponge, treated with chitosan, and treated with chitosan combined with rh-EGF. Immediate hemostasis was evaluated, and arterial healing was observed histologically. Results Groups B, C, and D showed a significant rate of immediate hemostasis as compared to group A (P<0.05), but there were no significant differences among groups B, C, and D. Histologically, only group D showed good continuity of the vessel wall after 1 week. It was the only group to show smooth muscle cell nuclei of the vessel wall. Conclusions We observed that chitosan has an effective hemostatic potential and the mix of rh-EGF and chitosan does not interfere with chitosan's hemostatic capabilities. We also identified enhanced healing of vessel walls when rh-EGF was added to chitosan. Further research based on these positive findings is needed to evaluate the potential use of this combination on difficult wounds like chronic diabetic ulcerations.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.683-690
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• 2011

The object of this study was to observe the effects of Hwanggeum-tang (HGT) aqueous extracts on Streptozotocin-induced rat's diabetes and related complications. Three different dosages of HGT extracts were orally administered oncea day for 28 days from 3 weeks after Streptozotocin treatment (60 mg/kg, single intraperitoneally administered). All the rats were checked at 3 weeks after Streptozotocin treatment as follows. Changes on the body weight, blood glucose level, kidney weight, serum BUN and creatinine level, liver weight, serum AST and ALT level, serum LDL, HDL, triglyceride and total cholesterol level were observed with changes on the pancreatic MDA content and GSH content. The results were compared with a potent antioxidant silymarin 100 mg/kg in which the effects on Streptozotocin-induced diabetes and related complications were already confirmed. As results of Streptozotocin-injected diabetes and related complications, dramatical decreases on the body weight, increase of the kidney and liver weight, increase of serum BUN, creatinine, AST, ALT, LDL, triglyceride, total cholesterol level and decreases of serum HDL level were detected in streptozotocin control as compared with intact control. In addition, marked increases of pancreatic MDA content and decreases of GSH content were also detected in streptozotocin control as compared with intact control. However, these diabetes and related complications, and inhibition of antioxidant effects induced by Streptozotocin were inhibited by 28 days continuous treatment of 50, 100 and 200 mg/kg of HGT extracts in the present study. HGT have favorable effects on the diabetes and various diabetic complications. Therefore, more detail mechanism studies should be conducedin future with the efficacy tests of individual herbal composition of HGT and the screening of the biological active compounds in herbs.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• 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.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.486-491
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• 2010

Tight control of blood glucose is the most important strategy for the treatment of diabetes mellitus. Here, we investigated the beneficial effects of Welsh onion on fasting and postprandial hyperglycemia. Inhibitory activities of hot water extracts from the green stalk and white bulb, which are the edible portions of the Welsh onion, and the fibrous root extract against yeast ${\alpha}$-glucosidase were measured in vitro. To study the effects of Welsh onion on postprandial hyperglycemia, a starch solution (1 g/kg) with and without Welsh onion fibrous root extract (500 mg/kg) or acarbose (50 mg/kg) was administered to streptozotocin-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the hypoglycemic effects of chronic feeding of Welsh onion, five-week-old db/db mice were fed an AIN-93G diet or a diet containing either Welsh onion fibrous root extract at 0.5% or acarbose at 0.05% for 7 weeks after 1 week of adaptation. Fasting plasma glucose and blood glycated hemoglobin were measured. Compared to the extract from the edible portions of Welsh onion, the fibrous root extract showed stronger inhibition against yeast ${\alpha}$-glucosidase, with an $IC_{50}$ of 239 ${\mu}g/mL$. Oral administration of Welsh onion fibrous root extract (500 mg/kg) and acarbose (50 mg/kg) significantly decreased incremental plasma glucose levels 30-120 min after oral ingestion of starch as well as the area under the postprandial glucose response curve, compared to the control group (P < 0.01). The plasma glucose and blood glycated hemoglobin levels of the Welsh onion group were significantly lower than those of the control group (P < 0.01), and were not significantly different from those fed acarbose. Thus, we conclude that the fibrous root of Welsh onion is effective in controlling hyperglycemia in animal models of diabetes mellitus.

• The Korean Journal of Food And Nutrition
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• v.18 no.2
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• pp.140-145
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• 2005

Changes of plasma lipids, total cholesterol and phospholipids content according to diet of silkworm extract powder were as follows. Decrease ratios of plasma lipids at 3, $5\%(w/w)$ treating groups were plasma lipids 5.16, $9.15\%$, those of total cholesterols were 1.63, $2.76\%$ and those of phospholipids were 1.37, $2.00\%$, respectively. Decreasing effects of plasma triglyceride content according to diet of silkworm extract powder was higher than those of total cholesterols and phospholipids contents. Decrease of plasma glucose concentrations were $4.62\%\;and\;6.46\%\;at\;3\%,\;5\%(w/w)$ treating group than control group, respectively. These results were not proportional decrease according to treating amount. In the other hand, changes of insulin concentration of plasma, pancreas and femur were appeared the similar tendency with plasma glucose concentration. Relationship between treating amount of silkworm extract powder and insulin concentration had not positive relativity, In conclusion, treatment of silkworm extract powder about $3\%(w/w)$ could be expected to prevention and/or medical treatment effect of diabetic patients.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.1
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• pp.75-86
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• 1998

Studies were conducted on anti-dibetic effect of the water extract from leaves of Eriobotryae folium, which had been used in Korea as a remedy for dibetes. The extract was found to inhibit the increase in the plasma level of sugar bu the not the decrease in the plasma level of insulin in alloxan-induced dibetic rats. Also, we investigated the in vivo effect of an aqueous extract (referred to as EF) from Eriobotryae folium on glucokinase and hexokinase activities of diabetes mellitus induced by interleukin-$1{\beta}$ ($IL-1{\beta}$). After 1 week of $IL-1{\beta}$ injection, the levels of serum glucose concentration and insulin secretion were dramatically increased. However, the insulin secretion was decreased with administration of EF. The level of glucose concentration was decreased by EF administration. Furthermore, it was observed that EF was effective in recovering the levels of insulin secretion. Enzyme activities of the glucokinase and hexokinase, which are key enzymes of glucose phosphorylastion, were decreased by $IL-1{\beta}$. EF administration to the mice allowed proportional increasing by stimulation of induction of enzyme activities as high as normal group. These results suggested that EF is highly effective in treatment of diabetes mellitus induce by $IL-1{\beta}$.

• Journal of Life Science
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• v.18 no.3
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• pp.329-335
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• 2008

Korean Deep ground sea-like water (KDSW) has a similar mineral composition with deep sea water. KDSW has demonstrated its usefulness and attracted in the medical fields. KDSW and Danasoo (desalted deep ground sea-like water) intake improve antioxidant, antidiabetic activity and immunity. Antioxidant activities of KDSW and Dnansoo were measured by using 2,2-diphenyl-l-picryl-hydrazyl (DPPH) free radical, superoxide dismutase-like activity (SODA) and photochemiluminescence (PCL). DPPH radical scavenging and SOD-like activities of KDSW and Danasoo were remarkably increased in a dose-dependent manner. Antioxidant activities of KDSW and Danasoo 85.32 and 14.02 nmol of ascorbic acid equivalent/ml KDSW and Danasoo, respectively, using the PCL method. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages RAW264.7 cells was inhibited up to 30% by treatment with Danasoo (20%). NO is synthesized by the enzyme of nitric oxide synthase (NOS) and plays an important role tumor growth and angiogenesis. The anticancer effects of Danasoo on human gastric and lung cancer cells was performed by levels of inducible nitric oxide synthase (iNOS). Danasoo significantly reduced iNOS expression of human gastric cancer (SNU-l) and lung carcinoma (A549). The serum glucose level was significantly reduced by Danasoo (20%) diet in streptozotocin (STZ)-induced diabetic rats. These result suggest that KDSW has excellent biological activities and thus it has great potential as a source for natural health products.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.10
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• pp.1257-1262
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• 2007

To develop basidiomycetes-fermented cereals with hypoglycemic property, inhibitory effects of basidiomycetes mycelia and basidiomycetes-fermented cereals on postprandial glucose were investigated. In vitro effect of basidiomycetes mycelia on retarding the membrane transport of glucose was compared with pectin. For basidiomycetes mycelia, $13.1{\pm}3.6{\sim}41.8{\pm}8.0%$ of total glucose remained in inner solution of dialysis membrane after dialysis for 120 min, indicating that most of basidiomycetes mycelia might effectively retard membrane transport of glucose. Glucose tolerance of basidiomycetes mycelia and basidiomycetes-fermented cereals was tested on streptozotocin-induced diabetic rats administrated with maltose. Postprandial glucose levels of basidiomycetes mycelia, $389.4{\pm}43.8{\sim}426.3{\pm}49.4mg/dL$, were considerably lower than that of control, $535.3{\pm}78.6mg/dL$, at 30 minutes after maltose administration. Namely, basidiomycetes mycelia showed better postprandial glucose lowering effect than pectin. Brown rice and barley fermented with Paecilomyces japonica showed much lower postprandial glucose level than raw brown rice and barley, especially hypoglycemic effect of barley fermented with Paecilomyces japonica was significant.