• Korean Journal of Food Science and Technology
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• v.38 no.5
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• pp.679-683
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• 2006

The effects of dried and fermented guava (Psidium guajava L.) leaf extracts on blood glucose levels were investigated in low-dose streptozotocin(STZ)-induced diabetic mice. Fermented guava leaf extract (500 mg/kg/day) significantly decreased the fasting blood glucose levels after 2-4 weeks of treatment and improved the impaired glucose tolerance in STZ-induced diabetic mice. On the other hand, dried guava leaf extract lowered the blood glucose levels and improved glucose tolerance two weeks after treatment, but exacerbated STZ-induced high blood glucose levels three and four weeks after treatment. Histological and immunohistochemical observation showed that fermented guava leaf extract treatment improved STZ-induced pancreatic beta-cell damage, but dried guava leaf extract did not affect the damage to the beta-cells. These results suggest that fermented guava (Psidium guajava L.) leaf extracts improve the hyperglycemia by protecting the pancreatic beta-cells hom damage in STZ-induced diabetic mice.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.559-563
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• 2003

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of $\beta$-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired $\beta$-cell function in high glucose condition. By the screening of various natural products blocking $\beta$-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced $\beta$-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of $\beta$-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.95.1-95.1
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• 2003

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved evidently as a potential remedy for type 2 diabetes mellitus. Both in vivo and in vitro experiments with water extract of Sopungsungi-won have been reported to exhibit anti-diabetic effects in our previous studies. In the present study, we have chosen Rheum undulatum (RU), which is the main component of Sopungsungi-won, to examine its anti-apoptotic effect on pancreatic b-cells, HIT-T15, against oxidative stress induced by hydrogen peroxide (H$_2$O$_2$). (omitted)

• Journal of Ginseng Research
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• v.41 no.1
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• pp.103-112
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• 2017

Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.126-126
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• 1998

Studies on natural products are of great interest, due to the limits in development of synthesized medicine and its side effects. Deer antler is the most popular cure-all type drug among Asian folk medicines. In this study, we newly isolated the biologically active components from chloroform extract and 70% ethanol extract of deer antler, and analyzed their structures. First, the structure of monoacetyldiglyceride in deer antler was identified. To investigate the structure-activity relationship of monoacetyldiglycerides, we synthesized diverse substituted glycerides from glycerol, and confirmed their structures by spectroscopic methods. Among seven structurally-interesting compounds tested in this study, compound 1,2,3,5, and 6 showed activity toward [Ca$\^$2+/]$\_$i/ increase in fura-2 loaded rat pancreatic acinar cells. Second, 70% ethanol extract of deer antler stimulated insulin release from rat pancreatic islets. We found the most effective fraction was CN-Es-8 in 70% ethanol extract, and it increased intracellular Ca$\^$2+/ concentration in pancreatic ${\beta}$-cell.

• Journal of Life Science
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• v.19 no.7
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• pp.923-927
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• 2009

Effects of deep sea water on blood glucose and the Langerhans' islet in STZ-induced type I diabetic mice were investigated. Results showed that diabetic symptoms in STZ-induced diabetic mice improve with a supplement of deep sea water. That is, the level of blood glucose was lower, the area of the Langerhan' islet was wider, and the number of pancreatic $\beta$-cells was larger in the diabetic mice supplied with deep sea water than in the diabetic mice supplied with tap water. Such effects might be related to the high level of Mg$^{2+}$ in the deep sea water.

• Journal of Acupuncture Research
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• v.26 no.6
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• pp.1-9
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• 2009

Objectives : For evaluation of preventive and anti-diabetic activities of Cinnamomi ramulus(CR) herbal acupuncture on pancreatic islet damage in streptozotocin(STZ)-induced diabetic rat. Methods : CR herbal acupuncture was performed at Bisu($BL_{20}$) for 3 weeks subcutaneously starting1 week before STZ i.p. injection. SD rats were divided into four groups(n=10 for each group); 1) NC group, non-treated normal control group, 2) STZ group, STZ administered control group, 3) CR125 group, CR(125mg/kg) + STZ administered group, and 4) CR250 group, CR(250mg/kg) + STZ administered group. Results : Both of CR250 and CR125 groups showed increase in insulin secretion and decrease in the level of serum triglyceride and non-esterified fatty acid in a dose-dependent manner compared to the STZ group. Only CR250 group showed decrease in the levels of glucose and total cholesterol compared to the STZ group. CR herbal acupuncture prevents $\beta$-cell damage of pancreatic islet, showing round figure on the sections of the pancreas. In the pancreatic cells, expressions of iNOS, JNK-2, P-JNK-1/2 and ERK-1/2 were decreased compared to the STZ group. CR herbal acupuncture solution did not show any cytotoxicity by MTS assay and inhibited expressions of iNOS and COX-2 in the STZ-induced diabetic rats. Conclusions : Therefore, we suggest that CR herbal acupuncture may act as a prophylactic as well as a therapeutic modality for diabetes mellitus.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.400-405
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• 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

• The Korean Journal of Food And Nutrition
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• v.25 no.1
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• pp.123-131
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• 2012

The objective of the present study was to evaluate the potential antidiabetic and antioxidant effect of the ethanol extract from Chrysanthemum cornarium L. var. spatiosum(CSE) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. In this study, the antidiabetic effect of CSE was examined using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide(MTT) cell proliferation assay, lactate dehydrogenase(LDH) release assay, $NAD^+$/NADH ratio and insulin secretion. To further investigate whether CSE is involved in the antioxidant activity of alloxan-damaged HIT-T15 cells, its antioxidant effect against alloxan-induced oxidative stress was measured in HIT-T15 cells by determining the levels of antioxidant enzymes including superoxide dismutase(SOD), glutathione S-transferase(GST), glutathione reductase(GR) and glutathione peroxidase(GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$/NADH ratio and insulin secretion in HIT-T15 cells. However, CSE significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular NAD+/NADH ratio and insulin secretion were also significantly increased by 1.7-fold and 1.3-fold, respectively, after treatment with 100 ${\mu}g/m{\ell}$ CSE. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while CSE significantly elevated the levels of antioxidant enzymes. These findings suggest that CSE could have a protective effect against cytotoxicity and dysfunction of pancreatic cells in the presence of alloxan-induced oxidative stress.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.1
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• pp.253-270
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• 2007

Objectives : This study has been carried out to understand the effect of Cimicifugae Rhizoma and Seungmagalgeuntang on the hyperglycemic mice induced with Streptozotocin(STZ). Methods : The 60mg/kg of STZ was fed into mice twice by 24 h interval and then 120mg/kg STZ was fed again 3 days after the earlier feeding, Control group was administered mice with 0.9% saline(2mL/kg/day), and experimental groups were administered Cimicifugae Rhizoma extract(CA group, 10mg/kg/day; CB group, 30mg/kg/day) or Seungmagalgeuntang(SA group, 10mg/kg/day; SB group, 30mg/kg/day) after hyperglycemic induction for 6 weeks. Results : The body weight of experimental groups higher than control. The blood glucose concentration of the control group increased continuously reaching to 298.9 mg/dL after 6 weeks, however, significantly(p<0.01 or p<0.05) decreased in the SA and SB groups compared with control group. Blood insulin level significantly(p<0.01) increased in the experimental groups. The activities of SOD and catalase were more decreased in the experimental group than control group compared with normal group. In the point of pancreatic immunohistochemical change, the experimental group's pancreatic islets have increased and enlarged and the concentration of insulin-positive beta cells has also increased, comparing with the control group. Meanwhile forms of nucleus and mitochondria in the experimental group's hepatic cells were almost similar to the normal group. Conclusion : The result from the six weeks of observation demonstrates that the extracts from Cimicifugae Rhizoma and Seungmagalgeuntang have positive effects on lowering blood sugar level and elevating insulin concentration. The extract had also effects on recovering and regenerating pancreatic tissue of the hyperglycemic mice induced with STZ. At the same time, it had a protective effect against hepatotoxicity as well.