• The Journal of Internal Korean Medicine
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• v.42 no.4
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• pp.605-621
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• 2021

Objectives: The purpose of this review is to assess the efficacy and safety of Hwangryunhaedok-tang for type 2 diabetes without complications by systemic review and meta-analysis of randomized controlled trials (RCTs). Methods: We searched the following up to March 31. 2021: PubMed, EMBASE, The Cochrane Library, CNKI, CiNii, KISS, KMBASE, OASIS, ScienceON. Data extraction and assessment of Cochrane's risk of bias (RoB) tool were performed by two independent authors, and if there was disagreement between two researchers, it was resolved through the intervention of a third researcher. Results: A total of seven trials are included in this systemic review. The treatment group (Hwangryunhaedok-tang plus conventional treatment) showed more statistically significant effects than did the control group (conventional treatment only) in fasting plasma glucose level, 2-hour postprandial plasma glucose level, glycated hemoglobin A1c, fasting insulin level, and HOMA-IR. There was no significant difference between the treatment group (Hwangryunhaedok-tang alone) and the control group (metformin alone). Conclusion: Hwangryunhaedok-tang might have efficacy and safety in controlling blood sugar level and improving insulin-resistance. However, the number of studies included in the meta-analysis was insufficient, and the Hwangryunhaedok-tang used in the included studies was not standardized. Also, the quality of the involved studies was generally low. Therefore, further studies are needed to determine the efficacy and safety of Hwangryunhaedok-tang treatment for type 2 diabetes mellitus.

• The Journal of Internal Korean Medicine
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• v.43 no.1
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• pp.22-40
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• 2022

Objectives: The purpose of this study is to assess the antidiabetic effect and safety of Galgunhwangryunhwanggum-tang for type 2 diabetes without complications by analyzing related research. Methods: For a systematic review and meta-analysis, we searched for the antidiabetic effect and safety of Galgunhwangryunhwanggum-tang for type 2 diabetes without complications in 10 databases up to September 2021. Only randomized controlled trials were chosen. Results: In the treatment effectiveness analysis and meta-analysis, Galgunhwangryunhwanggum-tang had significant improvement effects on fasting plasma glucose level, 2-hour postprandial glucose level, glycated hemoglobin, fasting insulin, and homeostasis model assessment for insulin resistance compared to the control group when treated in parallel with oral glycemic drugs. Conclusion: Galgunhwangryunhwanggum-tang is effective in improving blood sugar and insulin resistance in type 2 diabetes patients without complications and can especially be considered in parallel treatment with oral hypoglycemic drugs. A large-scale randomized controlled clinical trial is required to complement the limitations presented in this study in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.95-111
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• 2022

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

• Korean Journal of Food Science and Technology
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• v.42 no.3
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• pp.343-349
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• 2010

This investigation was conducted to assess the influence of Cirsium japonicum consumption on the plasma glucose and lipid profiles in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats weighing 230 g by injection of STZ into the tail vein at 45 mg/kg body weight. The rats were randomly assigned into four groups: a normal and STZ-control fed an AIN-93 diet group, and diabetic groups whose diets were supplemented with 10% Cirsium japonicum powder containing leaf or root for four weeks. To observe the effects of Cirsium japonicum in the animal model, the levels of glucose, cholesterol, HDL-cholesterol, triglyceride and free fatty acid in the plasma and the levels of glycogen in the tissue were determined after four weeks. Treatment of STZ-induced diabetic rats with leaf consumption significantly lowered the diet intake when compared with STZ-control rats. The relative weights of the liver and kidney differed significantly between the normal and diabetic groups. The weights of the kidneys in the leaf group were significantly lower than those in the STZ-control group. The level of hematocrit was also significantly lower in diabetic rats whose diets were supplemented with leaves when compared to those of STZ-control rats. The plasma glucose level was found to be significantly lower in the leaf group than the STZ-control group. The effect was significant after 2 weeks. The HDL-cholesterol levels increased in all of the diabetic experimental groups when compared to the STZ-control group. These results suggest that supplementation with Circicum japonicum leaves induced considerable hypoglycemic effect in STZ-induced diabetic rats and that these leaves may be useful for the management of diabetes mellitus.

• Journal of Nutrition and Health
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• v.37 no.4
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• pp.259-265
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• 2004

This study was designed to examine the effects of diets containing different levels of seeds of Benincasa hispida (wax-gourd)on plasma glucose, insulin levels and lipid profiles in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were induced diabetes mellitus by STZ injection (45 mg/kg) into the tail vein and were divide into 4 groups: normal, STZ-control, two experimental groups. Normal and STZ-control groups were fed an AIN-93 diet and 2 experi-mental groups were fed a modified diet containing 2.5% and 5.0% of wax gourd seed powder for 4 weeks. The weight gain and feed efficiency ratio in 5.0% seed groups were higher than in STZ-control group. A significant lowering effects of plasma glucose levels were observed in the wax gourd seed 2.5% and 5.0 groups. The plasma insulin level did not differ after treatment with wax gourd seed in experimental rats. The intake of 2.5% wax gourd seed did not result in sig-nificant change in plasma cholesterol levels compared to diabetic control group. The intake of 2.5% wax gourd seeds had normalized the increased levels of plasma triglyceride and free fatty acids after 4 weeks. In 5% wax gourd seed group, cholesterol, triglyceride and free fatty acid levels were elevated compared to 2.5% wax gourd seed group. The results of the present study indicate that 2.5% wax gourd seed group would be more effective to control the diabetes than 5% wax gourd seed group.

• Journal of Nutrition and Health
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• v.40 no.3
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• pp.199-210
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• 2007

The aim of this study was to investigate the effects of mulberry juice and cake powder on blood glucose and lipid status along with intestinal disaccharidase and erythrocyte antioxidative enzyme system in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing $100{\pm}10g$ were randomly assigned to one normal group, and eight STZ-induced diabetic groups: control diet group without mulberry juice and cake powders (DM-C), three mulberry juice powder groups (0.5%: DM-0.5J, 1%: DM-1J, 2%: DM-2J) and low mulberry cake powder groups (0.25%: DM-0.25C, 0.5%: DM-0.5C, 1%: DM-1 C, 2%: DM-2C). After three-week feeding of each experimental diet, diabetes was induced by intravenous injection of 50 mg/kg body weight of STZ in sodium citrate buffer (pH 4.3) via tail vein of eight DM groups. Rats were sacrificed at the 9th day of diabetic states. Level of blood glucose was 505 mg/dl in DM-C group but it was 28% and 39% lower in mulberry juice and cake powder fed groups, respectively, than the DM-C group. Activities of maltase, sucrase and lactase in proximal part of small intestine were significantly lower in the mulberry juice and cake powder groups by $42{\sim}47%$ than those of DM-C group. Erythrocytic superoxide dismutase, glutathione peroxidase and catalase activities were significantly reduced by STZ but increased close to normal levels along with less accumulation of thiobarbituric acid reactive substances (TBARS). Serum levels of triglyceride and total cholesterol and HDL-cholesterol by STZ-DM were reduced and increased respectively, to the norma] levels by the mulberry juice and cake powder. Except the levels of TBARS, the effects on the other measurements by the various dietary levels of mulberry juice and cake powder were almost same and the effect of the cake powder was most significant at the lowest level. These results indicate that mulberry juice and cake powders have consityerable hypoglycemic effect and strengthening antioxidant defense systems at the low levels in diabetic state and may be able to reduce diabetic complications.

• Journal of Nutrition and Health
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• v.38 no.10
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• pp.801-806
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• 2005

This study was designed to examine the effects of fractions of ethanol extract of Benincasa hispida (wax gourd) on plasma glucose and lipid levels in streptozotocin (STZ) induced diabolic rats. sprague-Dawley rats were induced diabetes mellitus by STZ injection (45 mg/kg) into the tail vein and were divided into 5 groups: normal, STZ-control, three experimental diabetic groups. fractions of ethanol extract of Benincasa hispida were administered orally into the diabetic rats for 14 days. The food intake and body weight were monitored and plasma levels of glucose, cholesterol, HDL-cholesterol, triglyceride (TG) , free fatty acid (FFA) , and aminotransferase activity were analyzed. A significant lowering effects of plasma glucose levels were observed in the chloroform fraction and $H_2O$ fraction group compared to STZ-control group at 14 days. Administrations of each of the three fractions decreased plasma TG and FFA levels in diabetic rats. Activity of alanine aminotransferase (ALT) in $CHCl_3$ fraction and $H_2O$ fraction groups and aspartate aminotransferase (AST) in $H_2O$ fraction group significantly lower than STZ-control group. The results show that $CHCl_3$ fraction of Benincasa hispida could be effective to control the STZ-induced diabetic rats. (Korean J Nutrition 38(10): 801$\sim$806,2005)

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.125-134
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• 1988

A single i.v. dose of streptozotocin (65 mg/kg) given to rats has produced a marked hyper-glycemia (>500 mg serum glucose/dl). Since the Atractylodis Rhizoma is known to have hypo-glycemic action, the water extracts of Atractylodis Rhizoma (ARWE) was given to the streptozotocin-induced (SZ) hyperglycemic rats. To determine whether ARWE has the anti-hyperglycemic effects, two different daily doses of ARWE (i.e.0.2 g/kg and 2.0 g/kg) were given orally to the SZ rats for up to 8 days. Thereupon, serum levels of glucose, insulin, amylase and cholesterol were determined on days 1, 3 and 8, following the initial and repeated daily administrations of ARWE. On day 8, glycogen content and glucose-6-phosphatase activity in the liver were assayed. Results showed that ARWE decreased the serum glucose levels, which had been markedly elevated by the SZ pre-treatment. In support of this, the serum insulin level, which had been quickly lowered by the SZ pre-treatment $(20{\mu}U/ml)$, was quickly elevated in the ARWE dose dependent manner that, at 2.0 g/kg ARWE, the serum insulin level was increased $(20{\mu}U/ml)$ above the normal level $(42{\mu}U/ml)$. Also, the serum amylase level, which was steadily decreasing after the SZ pre-treatment, was restored to the normal level folowing 8 day of ARWE (2.0 g/kg) treatment. Hepatic glycogen content and glucose-6-phosphatase activity, which decreased and increased, respectively in the 52 treatment group, were restored toward the normal level in SZ plus ARWE group.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.475-485
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• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Nutrition Research and Practice
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• v.1 no.4
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• pp.371-375
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• 2007

To control blood glucose level as close to normal is a major goal of treatment of diabetes mellitus. Hyperglycemia and hyperlipidemia are the major risk factors for cardiovascular complications, the major cause of immature death among the patients with type 2 diabetes. The purpose of this study is to determine the hypoglycemic and hypolipidemic effects of Salicornia herbacea in animal model of type 2 diabetes and to investigate the possible mechanisms for the beneficial effects of S. herbacea. S. herbacea was extracted with 70% ethanol and desalted with 100% ethanol. Three week-old db/db mice (C57BL/KsJ, n=16) were fed AIN-93G semipurified diet or diet containing 1% desalted ethanol extract of S. herbacea for 6 weeks after 1 week of adaptation. Fasting plasma glucose, triglyceride, and total cholesterol were measured by enzymatic methods and blood glycated hemoglobin ($HbA_{1C}$) by the chromatographic method. Body weight and food intake of S. herbacea group were not significantly different from those of the control group. Fasting plasma glucose and blood glycated hemoglobin levels tended to be lowered by S. herbacea treatment. Consumption of S. herbacea extract significantly decreased plasma triglyceride and cholesterol levels (p<0.05). The inhibition of S. herbacea extract against yeast ${\alpha}$-glucosidase was 31.9% of that of acarbose at the concentration of 0.5 mg/mL in vitro. The inhibitory activity of ethanol extract of S. herbacea against porcine pancreatic lipase was 59.0% of that of orlistat at the concentration of 0.25 mg/mL in vitro. Thus, these results suggest that S. herbacea could be effective in controlling hyperlipidemia by inhibition of pancreatic lipase in animal model of type 2 diabetes.