• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.49-56
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• 2016

To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic ${\beta}$-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-${\gamma}$, IL-$1{\beta}$,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE ($20{\mu}M$) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.494-500
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• 2014

BACKGROUND/OBJECTIVES: This study investigated whether Padina arborescens extract (PAE) protects INS-1 pancreatic ${\beta}$ cells against glucotoxicity-induced apoptosis. MATERIALS/METHODS: Assays, including cell viability, lipid peroxidation, generation of intracellular ROS, NO production, antioxidant enzyme activity and insulin secretion, were conducted. The expressions of Bax, Bcl-2, and caspase-3 proteins in INS-1 cells were evaluated by western blot analysis, and apoptosis/necrosis induced by high glucose was determined by analysis of FITC-Annexin V/PI staining. RESULTS: Treatment with high concentrations of glucose induced INS-1 cell death, but PAE at concentrations of 25, 50 or $100{\mu}g/ml$ significantly increased cell viability. The treatment with PAE dose dependently reduced the lipid peroxidation and increased the activities of antioxidant enzymes reduced by 30 mM glucose, while intracellular ROS levels increased under conditions of 30 mM glucose. PAE treatment improved the secretory responsiveness following stimulation with glucose. The results also demonstrated that glucotoxicity-induced apoptosis is associated with modulation of the Bax/Bcl-2 ratio. When INS-1 cells were stained with Annexin V/PI, we found that PAE reduced apoptosis by glucotoxicity. CONCLUSIONS: In conclusion, the present study indicates that PAE protects against high glucose-induced apoptosis in pancreatic ${\beta}$ cells by reducing oxidative stress.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.25-39
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• 2010

Background : At high glucose levels in $\beta$-cells, cell viability and insulin secretion are decreased by glucotoxicity. Sopyung-tang(SPT) had an effect on blood glucose level decrease and antioxidant enzyme activities in streptozotocin-induced diabetic rats. Objectives : This study performed a series of experiment to verify the effects of SPT extract on the cell viability, antioxidant enzyme activities, insulin secretion and insulin mRNA expression at hyperglycemic states of RIN-m5F. Methods : After treatment at various concentrations of SPT added to the RIN-m5F cells, cell viability by MTT assay, free radical-scavenging activity, SOD activity and insulin secretion were measured. Additionally, insulin-related gene expression was measured using real-time RT-PCR. Results : Compared to the control group, SPT extract showed considerable effects on RIN-m5F cell viability, DPPH radical-scavenging activity, superoxide dismutase (SOD) activity, insulin secretion and insulin-related gene expression. Conclusions : This study showed that SPT extract has an effect on $\beta$-cell cell viability, insulin secretion and insulin-related gene expression. Thus, SPT extract may be used for treatment of diabetes and its complications. Further mechanism studies of SPT seem to be necessary on the glucotoxicity and oxidative stress.

• Journal of Life Science
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• v.31 no.11
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• pp.969-979
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• 2021

Type 2 diabetes is a serious chronic metabolic disease, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent complications from diabetes. Hyperglycemia is a key pathologic feature of type 2 diabetes that mainly results from insulin resistance and pancreatic β-cell dysfunction. Chronic exposure of β-cells to elevated glucose concentrations induces glucotoxicity. In this study, we examined whether an 80% ethanol extract of Oxya chinensis sinuosa Mishchenko (OEE) protected INS-1 pancreatic β-cells against glucotoxicity-induced apoptosis and oxidative stress. Pretreatment with a high concentration of glucose (high glucose = 30 mM) induced glucotoxicity and apoptosis of INS-1 pancreatic β cells. Treatment with OEE significantly increased cell viability. Treatment with 0.01-0.20 mg/ml OEE dose dependently decreased intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels and increased insulin secretion in high glucose-pretreated INS-1 β cells. OEE also significantly increased the activities of antioxidant enzymes in response to high-glucose-induced oxidative stress. Moreover, OEE treatment significantly reduced the expressions of pro-apoptotic proteins, including Bax, cytochrome C, caspase-3, and caspase-9, and increased anti-apoptotic Bcl-2 expression. Apoptotic cells were identified using Annexin-V/propidium iodide staining, which revealed that treatment with OEE significantly reduced high-glucose-induced apoptosis. These findings implicate OEE as a valuable functional food in protecting pancreatic β-cells against glucotoxicity-induced apoptosis and oxidative stress.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.346-346
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• 2016

• CELLMED
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• v.8 no.3
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• pp.12.1-12.7
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• 2018

The study was designed to assess antioxidant and antidyslipidaemic effects of terpenoid-rich extract from the root of Aristolochia ringens V. Hyperglycemia-induced oxidative stress and dyslipidemia were established in rats by single intraperitoneal administration of 65 mg/kg bw streptozotocin. Based on therapeutic dose determined in previous study, streptozotocin-induced rats were orally administered with 75 and 150 mg/Kg bw of A. ringens extract for 14 days. Total protein, serum lipid profiles and biomarkers of oxidative stress in liver and kidney of the experimental rats were determined. Atherogenic and cardiovascular disease risk indices were computed. Streptozotocin-induced hyperglycaemia significantly (p < 0.05) decreased activities of superoxide dismutase, catalase and glutathione transferase as well as the amount of reduced glutathione in both tissues indicating oxidative stress induced kidney and liver injury due to glucotoxicity. In comparison to non-treated hyperglycaemic rats, activities of the antioxidant enzymes and concentration of glutathione-H were significantly (p < 0.0001) increased, whereas malondialdehyde was reduced in the tissues of rats treated with both 75 and 150 mg/Kg bw of the extract. The extract also caused significant (p < 0.001) reduction in elevated levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol levels, whereas concentration of the attenuated high density lipoprotein-cholesterol was increased in serum of the treated rats. Reduced atherogenic and cardiac risk indices were projected for the A. ringens extract-treated groups. Results from this study showed that extract from A. ringens root was rich in terpenoids and may reduce risks of complications associated with hyperglycemia-induced oxidative stress and dyslipidemia.

• Journal of Life Science
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• v.34 no.1
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• pp.9-17
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• 2024

Diabetes mellitus (DM) is one of the main global health problems. Chronic exposure to hyperglycemia can lead to cellular dysfunction that may become irreversible over time, a process that is termed glucose toxicity. Our perspective about glucose toxicity as it pertains to the pancreatic β-cell is that the characteristic decreases in insulin secretion are caused by regulated apoptotic gene expression. In this study, we examined whether ferulic acid protects INS-1 pancreatic cells against high glucose-induced apoptosis. High glucose concentration (30 mM) induced glucotoxicity and death of INS-1 pancreatic β cells. However, treatment with 1, 5, 10, or 20 μM ferulic acid increased the cell viability in a concentration-dependent manner. Treatment with ferulic acid dose-dependently decreased the intracellular levels of reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide in INS-1 pancreatic β cells pretreated with high glucose. These effects influence the apoptotic pathway, increasing the expression of the anti-apoptotic protein Bcl-2 and reducing the levels of pro-apoptotic proteins, including Bax, cytochrome C, and caspase 9. Annexin V/propidium iodide staining indicated that ferulic acid significantly reduced high glucose-induced apoptosis. These results demonstrate that ferulic acid is a potential therapeutic agent to protect INS-1 pancreatic β cells against high glucose-induced apoptosis.