• Nutrition Research and Practice
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• v.9 no.1
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• pp.22-29
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• 2015

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

• Proceedings of the Ginseng society Conference
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• 2007.12a
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

• Journal of Korean Neurosurgical Society
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• v.48 no.4
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• pp.319-324
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• 2010

Objective : The aim of this study was to analyze the correlation between thromboembolic complications and anti platelet drugs before and after neurointervention. Methods : Blood samples and radiographic data of patients who received a neurointervention (coil embolization, stent placement or both) were collected prospectively. Rapid platelet function assay-aspirin (RPFA-ASA) was used to calculate aspirin resistance in aspirin reaction units (ARU). For clopidogrel resistance, a P2Y12 assay was used to analyze the percentage of platelet inhibition. ARU > 550 and platelet inhibition < 40% were defined as aspirin and clopidogrel resistance, respectively. Results : Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures. The mean resistance values of all patients were 484 ARU and < 39%. Ten (17.0%) of 53 patients showed resistance to aspirin with an average of 597 ARU, and 33 (62.3%) of 53 patients showed resistance to clopidogrel with an average of < 26%. Ten patients demonstrated resistance to both drugs, 5 of which suffered a thromboembolic complication after neurointervention (mean values : 640 ARU and platelet inhibition < 23%). Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU, and mean clopidogrel resistances of < 33.8% and < 40.7%, respectively. Conclusion : Identifying individuals with poor platelet inhibition using standard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future. Neurointerventional research should focus on ideal doses, timing, choices, safety, and reliable measurements of anti platelet drug therapy, as well as confirming the clinical relevance of aggregometry in cerebrovascular patients.

• Preventive Nutrition and Food Science
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• v.5 no.3
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• pp.174-176
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• 2000

Seventeen wild vegetables consumed commonly in Korea were tested for inhibitory activities against alpha-glucosidase, followed by Bupleurum longeradiatum and Angelica decursiva. The hexane-soluble fractions of Hosta longipes, Ainsliaea acerifolia, Pedicularis resupinata, Bupleurum longeradiatum, and Angelica decursiva all at the concentration of 5 mg/ml, inhibited enzyme activity by greater than 50%, and the ethylacetate-soluble fractions of Hosta longipes, and Codonopsis lanceolata, and Bupleurum longeradiatum had relatively strong inhibitory activity against the enzyme. These results suggest that some edible plants merit further evaluation for clinical usefulness as anti-diabetic drugs.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.141-148
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• 2022

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• The Korean Journal of Pain
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• v.14 no.1
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• pp.98-103
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• 2001

Neuropathic pain originating from multiple condition of nerve cell injury is common, but is difficult to treat. Even though many drugs such as anti-convulsants, anti-depressants, NSAIDs, opioids have been used, their clinical analgesic action were not satisfactory due to occur severe side effects. Gabapentin was introduced in 1994 as a novel antiepileptic drug and has been used to treat partial seizure. After 1995 gabapentin treatment for reflex sympathetic dystrophy (RSD) started, 45% of the reports about the analgesic efficacy of gabapentin were restricted to the treatments of non-epileptic pain syndrome. This drug is preferred to treat neuropathic pain because of a lower incidence of its side effects than those of other anti-convulsants and anti-depressants. For evaluating it's analgesic efficacy, the changes in the patients' subjective pain intensity was measured by the score on the visual analogue scale (VAS) and patient's objective pain intensity by measuring the skin temperature via infrared thermography were investigated respectively. Side effects of gabapentin were look into. We observed successful relief of neuropathic pain in the three patients which included post-herpetic neuraligia, complex regional pain syndrome (CRPS) and diabetic neuropathic pain, and the side effects of gabapentin were at acceptable levels.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.401-408
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• 2011

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

• Korean Journal of Medicinal Crop Science
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• v.24 no.2
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• pp.115-120
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• 2016

Background: This study examined the hypoglycemic and kidney protective effect of black ginseng in streptozotocin-induced diabetic mice. Methods and Results: Diabetes was induced by treating mice with streptozotocin (STZ) for four weeks. In vivo studies were performed in order to investigate the hypoglycemic effect of the black ginseng prosapogenin (GBG05-FF) extract. The body weight and blood glucose level were measured. Moreover, after the mice were sacrificed, the kidneys were isolated and histological changes were observed with hematoxylin and eosin staining. Blood urea nitrogen and creatinine levels were also measured. The results showed that administration of black ginseng increased body weight. Compared to blood glucose levels in STZ mice, blood glucose levels were reduced by 48% in STZ mice supplemented with 300 mg/kg of black ginseng, and by 69% in STZ mice supplemented with 900 mg/kg. Furthermore, histopathological examination of STZ mouse kidneys revealed, changes in the kidneys, epithelial cell damages, inflammatory cell infiltration and glomerulus hypertrophy. However, a significant reduction of glomerular water droplets (indicative of glomerulus hypertrophy) was observed in the kidneys of STZ mice supplemented with black ginseng extract. Conclusions: These results suggest that black prosapogenin (GBG05-FF) ginseng extract has a significant hypoglycemic effect and can be used as an anti-diabetic substance and renal protective agents as part of dietary supplements or novel drugs.

• Korean Journal of Food Science and Technology
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• v.41 no.1
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• pp.77-81
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• 2009

This study examined the effects of black ginseng (9 times-steamed ginseng) on hypoglycemic action in streptozotocininduced diabetic rats as well as changes in ginsenoside composition by the steaming process. As the number of steaming cycles increased, the amounts of crude saponin and most ginsenoside contents decreased, while the amount of ginsenoside- Rg3 and the ratio of PD/PT (=[$Rb_1+Rb_2+Rc+Rd+Rg_3]/[Re+Rb_1+Rh_1]$) increased. This ginsenoside composition is a unique characteristic compared to other types of ginseng products. In order to investigate the hypoglycemic effect of the black ginseng extract, in vivo studies were performed in rats with streptozotocin-induced diabetes. The studies showed that the administration of the black ginseng extract decreased high blood glucose levels (more than 300 mg/dL) to a normal level (102 mg/dL). These results suggest that this black ginseng extract has a significant hypoglycemic effect and can be used as an anti-diabetic substance for dietary supplements or new drugs.