• Advances in Traditional Medicine
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• v.8 no.3
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• pp.302-310
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• 2008

Azadirachta indica A. Juss (N.O. Meliaceae), popularly known, as 'Neem' is an indigenous tree widely available in India. Almost every part of the tree has long been used in Unani system of medicine for the treatment of a variety of human ailments. The flowers have been mentioned as a remedy useful in controlling diabetes mellitus. The present study had been designed to investigate the hypoglycemic/anti-hyperglycemic effects of the methanolic extract of the flowers of A. indica (Gule-Neem) and its different fractions on normal, glucose fed hyperglycemic, adrenaline induced hyperglycemic and alloxan induced diabetic rats. The methanolic extract was resolved into water soluble and water insoluble fractions. Water soluble portion of the methanolic extract was found to possess significant blood sugar lowering effect in glucose-fed and adrenaline-induced hyperglycemic rats but it did not show such effect in normal and alloxan induced mild and severe diabetic rats. Water-soluble portion was fractionated by employing the polarity criterion with ethyl acetate and butanol. The ethyl acetate fraction was further fractionated into phenolic and non-phenolic fractions. Hypoglycemic effect of these fractions was also evaluated. The results suggest that the flowers of A. indica contain at least two different constituents, responsible for the said activity. These investigations validate the use of flowers of A. indica in diabetes by Unani physicians.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.430-434
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• 2017

BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1462-1469
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• 2007

This study has been carried out to understand the effect of Gangsim-tang on the hyperglycemic mice induced with Streptozotocin(STZ). The 60 mg/kg of streptozotocin(STZ) was treated into mice twice by 24 hrs interval and then 120 mg/kg STZ was treated again 3 days after the earlier treated. Control group was administered mice with 0.9％ saline(2ml/kg), and experimental groups were administered Gangsim-tang extract(GA group, 10 ㎎/㎏/day; GB group, 30 mg/kg/day) after hyperglycemic induction daily for 6 weeks. The body weight of experimental groups was lower than control. The blood glucose concentration increased continuously, reaching to 298.9 mg/dl after 6 weeks, however, experimental groups of the GA and GB groups significantly(p<0.01) decreased in the 4, 5, and 6 weeks groups. Blood glucose tolerance test was not significant between control and experimental groups. We examined the blood transaminase activities to know the effect of herbal medicine on liver function. The glutamic-oxaloacetic transaminase(GOT) activity was lower in group GB than in control. The glutamic-pyruvic transaminse(GPT) activity was lower in group GA and GB than in control. The superoxide dismutase(SOD) and catalase activities were higher in the group GA compared to control. The results of immunohistochemical study, Langerhan's islet of pancreas was destructed by treatment of STZ in the control, and a few of insulin positive cells observed in the control and experimental group. These results suggest that administration of Gangsim-tang extract to the hyperglycemic mice induced with STZ not regeneration of ${\beta}-cells$ but control of the blood glucose level.

• Nutrition Research and Practice
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• v.15 no.5
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• pp.591-603
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• 2021

BACKGROUND/OBJECTIVES: Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions. MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 µM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses. RESULTS: Hesperetin (0-100 µM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment. CONCLUSIONS: Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.

• Archives of Pharmacal Research
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• v.9 no.4
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• pp.219-222
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• 1986

Dose-dependent increasesin blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses ($10^{-8}M$/kg-$10^{-7}M$/kg); with higher dose ($10^{-6}M$/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yobimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated by alpha-1, alpha-2 and beta adrenoceptor. When clonidine (10$^{-6}$ M/kg) was administered simultaneously with sioproterenol ($10^{-6}M$/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation of alpha-2 adrenoceptor may be reponsible for the exertion of the hyperglycemic effect by beta agonists in fasted mice.

• Natural Product Sciences
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• v.15 no.1
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• pp.8-11
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• 2009

Blood glucose lowering effects of water extracts from four species of Commelinaceae(Commelina communis, Streptolirion volubile, Tradescantia reflexa, Aneliema keisak) were determined on alloxan-induced hyperglycemic rats. In all the experimental groups, the blood glucose level decreased after loading carbohydrates. The blood glucose level in a group treated with C. communis extract decreased significantly as compared with the normal group. After loading maltose and sucrose separately in different groups, the blood glucose level decreased in the groups treated with the extracts of C. communis and S. volubile, and remained approximately unchanged with the extracts of T. reflexa and A. keisak as compared with the control groups.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.271-276
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• 1995

Changes in the distribution of dopamine and its metabolites, activities of monoamine oxidase, and dopamine uptake were studied inhyperglycemic rat striatum. The hyperglycemia was induced by the administration of streptozotocin (STZ, 40 mg/kg, i.p. for 3 days.). The levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were significantly decreased without change in dopamine level in the synatic cleft 14 days after STZ treatment. In the synaptosome, the dopamine level, however, was significanly increased after the treatment. But the DOPAC level in the synaptosome was decreased 14 days after the treatment. The affinity of dopamine uptake was significantly decreased without changes in the velocity 14 days after the treatment. However the response to uptqke inhibitor was unchanged. The striatal monoamine oxidase activities were also decreased in the hyperglycemic state. These results indicate that various parameters of striatal dopamine activities were decreased in the hyperglycemic rats. Furthermore, it suggests that the increase in dopamine level of synaptosome might be due to the decrease in the release of dopaine in hyperglycemic state.

• Kosin Medical Journal
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• v.33 no.3
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• pp.402-408
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• 2018

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. In this study, we presented the case of a 59-year-old male who developed hyperosmolar hyperglycemic state (HHS), possibly caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents. This case highlights that HHS can develop in patients with diabetes treated with SGLT2 inhibitors.

• Journal of the East Asian Society of Dietary Life
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• v.18 no.4
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• pp.516-523
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• 2008

The effects of pan-fired (PM) and fermented (FM) Cudrania tricupidata tea leaves on $\alpha$-glucosidase inhibitory activity, oral glucose tolerance, blood glucose levels and serum lipids profiles in streptozotocin (STZ)-induced hyperglycemic rats were investigated. The $\alpha$-glucosidase inhibitory activity of FM ethanol extracts (20 mg/mL) was higher (92.5%) than that of raw dried leaves (RM) (69.1%) and PM (54.6%). In addition, the results of a glucose tolerance test revealed that the glucose levels of hyperglycemic rats that were fed PM and FM ethanol extracts and then orally administered glucose began to decrease after 60 minutes, but recovered after 120 minutes. However, the blood glucose levels in the hyperglycemic control group did not begin to decrease for 360 minutes. Additionally, the results of animal experiments that were conducted over five weeks to compare the dietary effects of PM and FM following hyperglycemic induction to the effects on the hyperglycemic control group (DM) were as follows: The body weight gain and FER of the treated rats were $12.9{\sim}16.9%$ higher than those of the DM group, whereas the amounts of feed and water intake by the treated rats were $6.8{\sim}10.1%$ lower. Additionally, the levels of blood glucose and serum fructosamine decreased by $27.3{\sim}39.8%$ and $6.7{\sim}20.0%$, respectively, in the treated rats. Moreover, the serum triglyceride, total cholesterol and LDL-cholesterol concentrations in the treated rats were $24.9{\sim}27.1%$, $15.9{\sim}17.4%$ and $33.8{\sim}38.4%$ lower, respectively. Finally, the HDL-cholesterol contents were $20.5{\sim}24.8%$ higher in the treated rats than in the control group. The above results suggest that PM and FM exerts an anti-hyperglycemic effect that occurs due to the inhibition of $\alpha$-glucosidase activity as well as via prevention and/or inhibition of changes in the serum lipid profile. In addition, the results of this study revealed that the synthetic anti-hyperglycemic effect of FM was greater than that of PM. However, further detailed studies are needed to confirm these results.

• YAKHAK HOEJI
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• v.39 no.5
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• pp.528-534
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• 1995

This investigation was aimed at the study of the antidiabetic activity and effect on hepatic glutathione metabolism of polysaccharide from Trichosanthes kirilowii in hyperglycemic rats with aboxan (175 mg/Kg, i.p.). As the results, the polysaccharide inhibited the increase of blood glucose, triglyceride level and lactate dehydrogenase activity, but cholesterol not changed. And it increased protein bound-SH, nonprotein bound-SH, glutathione level and inhibited the decrease of glutathione S-transferase.