• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.163-171
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• 2020

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

• Polymer(Korea)
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• v.34 no.6
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• pp.527-533
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• 2010

The pioglitazone loaded poly(lactide-co-glycolide)(PLGA) nanospheres were prepared by emulsion-evaporation method and optimized for particle size and entrapment efficiency. The optimized particles were 125~170 nm in size with narrow size distribution and showed above 85% entrapment efficiency at 30% of pioglitazone loading when prepared with 3% w/v of poly(vinyl alcohol) (PVA) as a surfactant. These particulate carriers exhibited a controlled in vitro release of pioglitazone for 40 days at a nearly constant rate. The pioglitazone loaded PLGA nanospheres were not only effective to reduce the blood sugar level of diabetic rats but also non-toxic for the animal body, in particular for sensitive organs like kidney, liver, heart, lung and spleen. These results indicate that PLGA nanospheres have a great potential for oral delivery of pioglitazone.

• The Korean Journal of Mycology
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• v.30 no.2
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• pp.131-135
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• 2002

The optimum conditions for the production of Lentinus edodes mycelia and it's hypoglycemic effect was studied. Optimum pH and temperature for the production of mycelia in shaken flask culture were 5 and $30^{\circ}C$, respectively, for 24 days cultivation. Culture period for maximum production of mycelia (8.13 g/l) in 5-l jar fermenter cultivation was shortened as much as 6 days compared to shaken flask culture. The mycelial dose of 5 % proved almost equally effective in lowering the plasma glucose, total cholesterol, and triglyceride level as much as 23.0, 20.7, and 27.1%, respectively. The values of alanine transaminase and aspartate transaminase were also estimated and exhibited a substantial reduction (29.6 and 34.3%, respectively) in activity after the administration of dried mycelia.

• Korean journal of food and cookery science
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• v.10 no.4
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• pp.412-419
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• 1994

The Contents of proximate compositions, vitamin C and minerals(Ca, P, Fe and Zn) of five Korean wild vegetables were analyzed. Twenty four cooking recipes with three of the vegetables were developed and their taste characteristics were evaluated by 12-trained panels. The five Korean wild vegetables are Cassia tora(C.t.), Lycium chinese Mill(L.c.), Trichosanthes quadricirra MIQ(T.q.), Polygonatum japonicum MORR et DECAIS(P.j.) and Articum lappa L.(A.l.). They have been known as the efficacious plants agaginst diabetes mellitus. In our previous work, their hypoglycemic effects have been studied through streptozotocin-induced diabetic rats and fed on the wild vegetables. Contents of moisture were 14~86% in the samples and L.c. showed relatively higher content of crude protein(16.4%). High level of crude fat was seen in C.t.(9.4%). Contents of vitamin C were also relatively high in the wild vegetables(14.2~42.0 mg%). Analysis of minerals revealed the high level of Ca in L.c. leaves, P in A.l. and Fe in C.t. and L.c. leaves. All of the samples contained Zn in 5.0~14.6 mg%. Twelvetrained taste panels indicated that the 24-preparations of L.c. leaves, fruites and P.j. were well accepted in taste, color and odor. Although L.c. fruit gruel, L.c. cream soup and P.j. saute were evalulated as less acceptable, their sensory scores were in 3.6~5.4 which were not undesirable. The newly developed cooking recipes of L.c. fruits and leaves showed better scores in color and texture, P.j. in texture and odor.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.279-286
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• 2017

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-${\beta}$-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

• Journal of Environmental Science International
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• v.29 no.8
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• pp.837-846
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• 2020

In present study, we investigated the antidiabetic effect of Momordica charantia(as well known "bitter melon"). This study was conducted to determine antidiabetic mechanism of Bitter Melon Extract (BME). We measured blood glucose, insulin, glucagon level in a Sprague-Dawley rat model of high-fat diet/streptozotocin(HFD/STZ)-induced diabetes. Five experimental groups were used: normal, HFD/STZ, BME 62.5 mg/kg HFD/STZ, BME 125 mg/kg HFD/STZ and BME 250 mg/kg HFD/STZ. BME was orally administered to the rats every other day for 9 weeks. Results showed that fasting blood glucose levels were significantly lower in the BME 125 mg/kg(150.17 ± 20.22 mg/dL) and 250 mg/kg(124.17 ± 22.17 mg/dL) groups than in the vehicle group(188.83 ± 26.63 mg/dL)(p<0.05). In addition, glucagon levels were lower in the three BME treatment groups than in the vehicle group(p<0.05). Oral glucose tolerance tests revealed that the BME 250 mg/kg group had significantly(p<0.05) reduced 120-minute blood glucose levels and areas under the curve. Our results suggest that BME induces antidiabetic effects via the reduction of glucagon and blood glucose levels.

• 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.