• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.5
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• pp.552-561
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• 2017

This study aimed to investigate glucose uptake mechanisms and metabolic mechanisms for absorbed glucose in HepG2 cells treated with Acanthopanax senticosus water extract (ASW). A colorimetric assay kit was used to measure polyphenol content, glucokinase (GK) activity, glucose uptake, glucose consumption in cell culture medium, and glycogen content. RT-PCR and western blotting were performed to examine changes in the expression levels of glucose transporter 2 (GLUT2), hepatocyte nuclear factor $1{\alpha}$ ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phospho-AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase, GK, and glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$). Increased glucose uptake upon ASW treatment was confirmed to result from increased expression of $HNF-1{\alpha}$, which is one of the transcription factors acting on the GLUT2 promoter. From the measurements of GK activity, we observed that ASW had an effect on glucose phosphorylation, and we also confirmed that increased AMPK phosphorylation promoted glycolysis and suppressed gluconeogenesis. We confirmed that the increase in glycogen upon ASW treatment was induced by activation of Akt by PI3k, followed by phosphorylation of $GSK3{\beta}$. This study demonstrates that ASW activates glucose metabolic mechanisms in liver cells and is therefore a potential candidate to alleviate diabetes.

• Journal of Pharmacopuncture
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• v.26 no.1
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• pp.27-37
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• 2023

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.19 no.10
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• pp.243-253
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• 2018

This study aimed to investigate the effects of DCI on glucose control, quality of life(SF-36 Version 2.0, Korean) and SDSCA(Summary of Diabetes Self-Care Activities) in patients with type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled study was performed on 46 patients with HbA1c 7.0% taking triple anti-diabetic drug regimen who visited the department of Endocrinology and Metabolism in Chungnam National University Hospital between March 2015 and May 2016. As a result, DCI treatment in the intervention group resulted in significantly reduced HbA1c levels $8.75{\pm}0.79%$(baseline), $8.36{\pm}1.03%$(after 12weeks), and $8.65{\pm}0.81%$(after 24weeks). However, patients in the control group did not show any significant change. Interestingly, both DCI treatment group and the control group significantly showed improvements in SDSCA. Participants in the intervention group showed a small yet significant improvement in their only fasting blood glucose test in SDSCA and revealed significant increase in the quantitative levels of quality of life, from $73.05{\pm}16.85$ to $82.74{\pm}10.68$. By using pathway analysis, improvement of SDSCA scores(${\beta}=-0.505$, t=-2.743) was the most influential factor to the fasting blood glucose. The quality of life of patients with type 2 diabetes mellitus was affected by changes of SDSCA scores(${\beta}=0.411$, t=2.024) and fasting c-peptide(${\beta}=-0.445$, t=-2.668) in DCI treatment group. In conclusion, treatment of DCI effectively improved glucose control in patients with type 2 DM(HbA1c level>7.0%) after 12 weeks of treatment, although it had no impact on glucose control after 24 weeks of treatment. Improved glucose control may encourage diabetic patients to conduct self-care activities and improve the quality of life. Based on the present study, we suggest that diabetes self-management, as well as consideration of comprehensive laboratory findings, may be important factor in regulating the quality of life in type 2 DM patients.

• Korean Journal of Food Science and Technology
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• v.42 no.2
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• pp.210-216
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• 2010

Rosa rugosa has traditionally been used as a folk remedy for diabetes. The objective of this study was therefore to demonstrate the inhibition of endothelial dysfunction activities through antioxidants and the anti-glycation of Rosa rugosa roots. Dried roots of Rosa rugosa were boiled in methanol for three hours, evaporated and lyophilized with a freeze-dryer. The methanolic extract of Rosa rugosa roots (RRE) was tested for antioxidant activities by measuring total polyphenol (TP) content, flavonoid content, 1,1-diphenyl-2-picrylhydrazyl free radical-scavenging activity (DPPH) assay, and ferric-reducing antioxidant power (FRAP) assay. The total TP content, flavonoid content, FRAP value, and $DPPHSC_{50}$ are $345.2\;{\mu}g$ gallic acid equivalents/mg dry matter (DM), $128.1\;{\mu}g$ quercetin equivalents/mg DM, 2.2 mM $FeSO_4$/mg DM and $34.2\;{\mu}g$ DM/mL, respectively. Treatment of RRE significantly lowered fluorescent formation due to advanced glycation reaction. In addition, reactive oxygen species (ROS) scavenging assay, monocyte adherent assay and transendothelial electrical resistance (TEER) assay were performed to investigate the possibility that RRE improves endothelial dysfunction-induced diabetic complications. The adhesion of THP-1 to treated HUVEC with RRE ($100\;{\mu}g/mL$; 33% and $500\;{\mu}g/mL$; 75%) was significantly reduced compared to HUVEC stimulated by glyceraldehydes-AGEs (advanced glycation end product). The TEER value ($88\;{\Omega}{\cdot}cm^2$) of stimulated HUVEC by glyceraldehydes-AGEs was reduced compared to non-stimulation ($113\;{\Omega}{\cdot}cm^2$). However, normalization with RRE increased endothelial permeability in a dose-dependent manner ($100\;{\mu}g/mL$; $102\;{\Omega}{\cdot}cm^2$ and $500\;{\mu}g/mL$; $106\;{\Omega}{\cdot}cm^2$). Thus, these results suggest that Rosa rugosa roots could be a novel candidate for the prevention of diabetic complications through antioxidants and inhibition of advanced glycation end product formation.

• Food Science and Preservation
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• v.22 no.2
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• pp.275-280
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• 2015

Among the naturally occurring antioxidants, polyphenols are widely distributed in various fruits, vegetables, wines, juices, and plant-based dietary sources and divided into several subclasses that included phenolic acid, flavonoids, stilbenes, and lignans. As part of our continuing search for bioactive food ingredients, the antioxidant and ${\alpha}$-glucosidase inhibitory activities of the aqueous ethanolic extract from the aerial parts of Ainsliaea acerifolia were investigated in vitro. The antioxidant properties were evaluated via radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) ($ABTS^+$) radicals. In addition, the anti-diabetic effect of A. acerifolia extracts was tested via ${\alpha}$-glucosidase inhibitory assay. Furthermore, the total phenolic contents were determined using a spectrophotometric method. All the tested samples showed dose-dependent radical scavenging and ${\alpha}$-glucosidase inhibitory activities. In particularly, the ${\alpha}$-glucosidase inhibitory and radical scavenging properties of the ethyl acetate (EtOAc)-soluble portion from the aerial parts of the A. acerifolia were higher than those of the other solvent-soluble portions. These results suggest that A. acerifolia could be considered a new potential source of natural antioxidants and antidiabetic ingredients. More systematic investigation of the aerial parts of A. acerifolia will be performed for the further development of anti-oxidative and antidiabetic drugs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.642-650
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• 2016

Cynanchi wilfordii Radix (CW) and Perilla sikokiana (PS) were extracted under different conditions to study their antioxidant, anti-diabetic, and anti-obesity activities. Their potentials as functional food ingredients were investigated. The highest total phenol contents were $15.74{\pm}0.69mg/g$ for CW100 [100% fermented ethanol (FE) extract from CW] and $39.37{\pm}3.46mg/g$ for PS50 (50% FE extract from PS). When extracts were processed at 1 mg/mL, DPPH radical scavenging activities were $79.79{\pm}0.79%$ and $82.69{\pm}1.07%$, respectively, at CW100 and PS50. ABTS radical scavenging activities were $80.20{\pm}2.86%$ and $75.00{\pm}1.78%$, respectively, at CW100 and PS50. However, ferric reducing antioxidant power activities at 1 mg/mL were higher than 80% for PS under all extraction conditions. The highest ${\alpha}$-amylase inhibitory activities were $51.56{\pm}0.56{\sim}59.2{\pm}1.13%$ at CW50 and $46.70{\pm}0.32{\sim}66.17{\pm}0.55%$ at PS0. Cell differentiation inhibitory effects in 3T3-L1 adipocytes were $29.49{\pm}2.98%$ at CW100 and $23.31{\pm}0.61%$ at PS50. The inhibitory effect of the CW100-PS50 mixture was $43.03{\pm}1.63%$, which was significantly higher than those of individual extracts.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.522-529
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• 2014

Sea tangle (Laminaria japonica) is well known as having anti-diabetic and hypolipidemic effects in animals as well as in humans. In this study, we evaluated the effects of sea tangle-added patty on postprandial blood glucose and lipid profiles in borderline-hypercholesterolemic (cholesterol ${\geq}200$ mg/dL) adults. Eleven subjects voluntarily participated in the experiment, and each subject provided written consent. Experimental patty (E) was made by adding 2.25 g of sea tangle powder as a substitution to 1.125 g each of pork and chicken. In the first week, 200 g of Control patty (C) was provided to each subject, who had fasted more than 12 hours. In the second week, the same amount of E patty was supplied under the same conditions. Serum glucose levels increased significantly less at 30, 60, and 120 min after consumption of E patty compared to the levels at all time points after eating C patty. Thus, the change in the area under curve (${\Delta}AUC$) of serum glucose levels through 120 minutes was lower when consuming E patty compared to C patty. Although serum C-peptide concentrations were not significantly different at all time points between the two patties, the ${\Delta}AUC$ of serum C-peptide concentrations through 120 minutes was lower when consuming E patty compared to C patty. However, there were no differences in serum levels of triglyceride, total cholesterol, LDL-C, and HDL-C at 30, 60, 120, 180, and 240 min between the two patties. Further, each ${\Delta}AUC$ of these lipid levels through 240 minutes was not significantly different between the two patties. The results indicate that sea tangle-added patty may decrease postprandial plasma glucose concentrations and reduce insulin secretion, although it might not ameliorate serum lipid profiles in adults with borderline-hypercholesterolemia.

• Journal of Life Science
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• v.27 no.5
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• pp.509-516
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• 2017

Perilla frutescens (L.) Britton var. sprouts (PFS) is a plant of the labiatae family. The purpose of this work was to assess the preventive effects of PFS ethanolic extracts (PFSEs) on cytokine-induced ${\beta}$-cell damage. Cytokines, which are released by the infiltration of inflammatory cells around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. The combination of interleukin-$1{\beta}$ (IL-1), interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) induced formation of reactive oxygen species (ROS). Accumulation of intracellular ROS led to ${\beta}$-cell dysfunction and apoptosis. PFSEs possess antioxidant activity and thus lead to downregulation of ROS generation. Cytokines decrease cell viability, stimulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and induce the production of nitric oxide (NO). PFSEs prevented cytokine-induced cell viability in a dose-dependent manner. Incubation with PFSE resulted in significant reduction in cytokine-induced NO production that correlated with reduced levels of the iNOS and COX-2 protein expression. Furthermore, PFSE significantly decreased the activation of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) by inhibition of $I{\kappa}B{\alpha}$ phosphorylation in RINm5F cells. In summary, our results suggest that the protective effects of PFSE might serve to counteract cytokine-induced ${\beta}$-cell destruction. Findings indicate that consumption of Perilla frutescens (L.) Britton var. sprouts alleviates hyperglycemia-mediated oxidative stress and pro-inflammatory cytokine-induced ${\beta}$-cell damage and thus has beneficial anti-diabetic effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.3
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• pp.321-327
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• 2006

This study was performed to investigate the hypoglycemic effect of pine needle extract oil against type 2 diabetes. Six-week-old male C57BL/Ks(db/db) mice were divided into four groups : negative control, pine needle extract oil low dose, high dose and positive control groups, which fed daily for 6 weeks with corn oil, pine needle extract oil 112.5 mg/kg, 450 mg/kg or metformin (150 mg/kg ), respectively. The oral administration of the pine needle extract oil resulted in the significant and dose-dependent decreases of blood glucose levels in comparison with corn oil treatment. The levels of HbAlc showed a tendency of the decrease by the high dose treatment of the pine needle extract oil and were positively correlated with blood glucose levels (r=0.5046, p=0.0023) . However, the levels of serum insulin and C-peptide were not affected by pine needle extract oil or metformin treatments. The levels of serum leptin, which is related with the insulin sensitivity, showed a tendency of the increases by pine needle extract oil treatment and were negatively correlated to blood glucose levels (r=-0.4754, p=0.0052). In conclusion, these results suggest that the pine needle extract oil have a potential for the oral anti-hyperglycemic agent and the mode of action may be related with the improvement of the insulin sensitivity through blood leptin.