• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• Journal of Life Science
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• v.25 no.11
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• pp.1311-1318
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• 2015

The effects of fruit maturation on changes in the total phenolics, flavonoids, and carotenoids of methanolic extracts of Citrus sudachi, in addition to its antioxidant and antidiabetic activities, were determined. Generally, the concentration of these chemical constituents increased as C. sudachi reached maturity. C. sudachi contained high levels of total phenolics, flavonoids, and carotenoids at maturity, contributing 6339.5 mg of gallic acid equivalent per 100 g, 2364.2 mg of rutin equivalent per 100 g, and 678.7 mg/ml, respectively. The scavenging activities of 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydrogen peroxide and nitric oxide radicals and the reducing power of mature fruits were significantly higher at all data points than those of immature fruits (p<0.05). In contrast, the ferrous ion chelating activity of mature and immature C. sudachi fruits was similar. The 50% effective concentrations (EC₅₀) of mature fruits were 4.1±0.10 mg/ml for scavenging DPPH radicals, 3.1±0.02 mg/ml for scavenging hydrogen peroxide, 3.9±0.01 mg/ml for scavenging nitric oxide, and 3.8±0.02 mg/ml for chelating ferrous ion. The antidiabetic activity of C. sudachi was studied in vitro using the α-glucosidase inhibitory method. The inhibitory activity of mature C. sudachi fruits on α-glucosidase was higher than that of immature fruits. These results suggest that the content of bioactive compounds and the antioxidant and antidiabetic activities of C. sudachi change during maturation. These findings can be further extended to exploit them for their possible application for the preservation of food products, as well as their use as health supplements and nutraceuticals.

• Proceedings of the Korean Nutrition Society Conference
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• 2003.10a
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• pp.162-162
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• 2003

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.177.2-177.2
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• 2003

Thiazolidinediones (TZDs) are a new class of compound that increase insulin sensitivity in type 2 diabetic patients. Thiazolidinediones (TZDs) act as ligands for a member of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptor-$\gamma$ (PPAR-$\gamma$), which is highly expressed in fatty tissue and, moreover, has been shown to play an important role in fat cell differentiation. The strong interaction between the antidiabetic activity ofTZDs and their ability to activate PPAR-$\gamma$ suggests that PPAR-$\gamma$, through downstream-regulated genes, mediates the effects of TZDs. (omitted)

• Biomedical Science Letters
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• v.18 no.4
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• pp.345-354
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• 2012

Angelica keiskei has exhibited numerous pharmacological effects including antitumor, antimetastatic, and antidiabetic effects. However, the anti-inflammatory effects and mechanisms employed by xanthoangelol E isolated from Angelica keiskei are incompletely understood. In this study, we attempted to determine the effects of Xanthoangelol E on the lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophage. The findings of this study demonstrated that xanthoangelol E inhibited the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and prostaglandin $E_2$ ($PGE_2$). Xanthoangelol E inhibited the enhanced levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) caused by LPS. Additionally, we showed that the anti-inflammatory effect of xanthoangelol E is through the regulation of the activation of nuclear factor (NF)-${\kappa}B$ and caspase-1. These results provide novel insights into the pharmacological actions of xanthoangelol E as a potential candidate for the development of new drugs to treat inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.351-359
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• 2009

Etiological studies of diabetes and its complications showed that oxidative stress might play a major role, Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Mori Fructus extract has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs, The aim of this study was to investigate the effect of Mori Fructus extract in male ob/ob mouse with severe obesity, hyperinsulinemia, hyperglycemia, hyperlipidemia. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57BL/6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus extract per 1 kg of body weight for 14 days. The effects of Mori Fructus extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Western blotting was performed using anti-AGE, anti-RAGE respectively. Mori Fructus extract lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Mori Fructus extract treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the generation of ROS in the kidney. MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the expression of AGE, RAGE in the ob/ob mice. The results suggested that Mori Fructus exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging the ROS, decreasing the MDA+HAE level, increasing the GSH level and inhibiting the expression of AGE, RAGE in the ob/ob mice.

• Journal of the East Asian Society of Dietary Life
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• v.25 no.2
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• pp.270-277
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• 2015

This study was performed to investigate the antidiabetic and antioxidant activities of Crataegus pinnatifida which was extracted with water and different concentrations of EtOH (0~100%). The extraction yield of 70% EtOH (33.16%) was higher than that of 50% EtOH (27.79%), water (21.71%), 30% EtOH (21.88%) and 100% EtOH (19.03%). Total polyphenol contents of 50% EtOH extract from C. pinnatifida were the highest. DPPH and ABTS radical scavenging activities were $80.79{\pm}0.83%$ and $34.92{\pm}0.97%$ in 50% EtOH extract, respectively, which were higher than those of other extracts. The inhibitory activities of 50% ethanol extract from C. pinnatifida against advanced glycation end products (AGEs) formation and ${\alpha}$-glucosidase were determined to be $27.09{\pm}2.27%$ and $58.87{\pm}0.70%$, respectively. The inhibitory activity of water extract from C. pinnatifida against aldose reductase was higher ($30.68{\pm}1.41%$) than those of other extracts. Overall, 50% EtOH extract from C. pinnatifida showed the highest antidiabetic and antioxidant effects. These results suggest that 50% ethanol extracts from C. pinnatifida have potential as a useful ingredient with antidiabetic and antioxidant effects.

• Food Science and Preservation
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• v.18 no.6
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• pp.923-929
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• 2011

For the purpose of investigating the in vitro antidiabetic activity of a medicinal herb mixture prepared through traditional antidiabetic prescription, the study analyzed the existence of insulin-similar components and examined ${\alpha}$-amylase and ${\alpha}$-glucosidase inhibition activity. As a result of arranging the medicinal herb mixture extracts over the 3T3-L1 fibroblast in the concentration of $10{\mu}g/mL$, which confirmed that it included much of insulin sensitizer components as 151.7% in the differentiation of 3T3-L1 fibroblast. The inhibition activity against ${\alpha}$-amylase of the medicinal herb mixture extracts as hypoglycemic agent were 38.4, 31.5 and 16.6% in the concentration of 10.0, 1.0 and 0.1 mg/mL, respectively. The inhibition activity against ${\alpha}$-glucosidase of the medicinal herb mixture extracts were 81.3, 35.8 and 26.7% in the concentration of 10.0, 1.0 and 0.1 mg/mL, respectively. The inhibition activity against ${\alpha}$-glucosidase in the ethyl acetate fractions of the water and 80% ethanol extracts were 66.9% and 55.1%, respectively, the highest levels in the various solvent extracts.

• The Journal of Korean Medicine
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• v.28 no.3 s.71
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• pp.57-69
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• 2007

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications have shown that oxidative stress might play a major role. Therefore, many methods have been tried to regulate free oxygen radicals for treating diabetes and its complications. Ojung-hwan, composed of five crude herbs, has been considered effective for treating symptoms of aging. In male ob/ob mouse of severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activities and mechanisms of Ojung-hwan were examined. Methods : Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. The effects of Ojung-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical (${\cdot}\;O{_2}{^-}$), MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Results : Ojung-hwan lowered the levels of serum glucose and insulin in a dose-dependent manner. Total cholesterol, triglyceride and free fatty acid levels decreased, while the HDL-cholesterol level increased, in Ojung-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities increased in the ob/ob mice, whereas they were inhibited in the Ojung-hwan treated groups. Ojung-hwan inhibited the generation of ${\cdot}\;O{_2}{^-}$ in the kidney. Finally, MDA+HAE levels increased and GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Ojung-hwan treated groups. Conclusions : Ojung-hwan showed antidiabetic and antihyperlipidemic activities by regulating theactivities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.