• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.14-14
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• 2018

This Camptotheca acuminata Decne. (CA), belonging to Nyssaceae, is a deciduous tree. and has been used as Traditional Chinese medicine since ancient times. The CA produces camptothecin a natural indole alkaloid, and reported to have anti-cancer effects. But the studies on biological activities of CA leaves are insufficient. Therefore, this study confirmed various biological activities such as antioxidant, antidiabetic, anticancer, antiinflammatory and metabolism analysis by HPLC-MS/MS of CA leaves. The $RC_{50}$ values of DPPH radical scavenging activity of ethyl acetate fraction, n-Butanol fraction, methanol extraction, water fraction and n-Hexane fraction were $12.23{\pm}0.01$, $15.93{\pm}0.42$, $55.12{\pm}0.45$, $56.29{\pm}4.15$ and $427.29{\pm}6.13ug/mL$, respectively. The $IC_{50}$ values of ${\alpha}$-glucosidase inhibitory activity of ethyl acetate fraction, n-Butanol fraction, methanol extraction, n-Hexane fraction and water fraction were $24.29{\pm}0.14$, $47.86{\pm}0.45$, $54.23{\pm}1.21$ $466.76{\pm}2.21$ and $623.91{\pm}9.67ug/mL$, respectively. The nitric oxide release activity of n-Hexane fraction, methanol extraction, ethyl acetate fraction, water fraction and n-Butanol fraction were $31.49{\pm}5.74$, $29.79{\pm}0.71$, $26.89{\pm}0.71$, $8.24{\pm}5.83$ and $7.75{\pm}4.08%$ at 25 ug/mL, respectively. The anti-cancer activity of n-Hexane fraction, methanol extraction, ethyl acetate fraction, water fraction and n-Butanol fraction were $31.49{\pm}5.74$, $29.79{\pm}0.71$, $26.89{\pm}0.71$, $8.24{\pm}5.83$ and $7.75{\pm}4.08%$ at 25 ug/mL, respectively. The ethyl acetate fraction activities showed higher biological activities than other fractions. Thus, Additional studies were conducted using ethyl acetate fraction. Metabolite analysis was performed using a LCMS-8040 triple quadrupole mass spectrometer. As a result, Five compounds (1-5) were identified in the ethyl acetate fraction of the CA leave. The identification of these compounds was generated by the analysis of fragmentation methods of the negative and positive ion modes. Five compounds were identified as gallic acid (1), chlorogenic acid (2), isoquercetin (3), astragalin (4) and camptothecin (5). These results suggest that the CA leave can be used for functional materials.

• Journal of Life Science
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• v.32 no.10
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• pp.762-770
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• 2022

Hyperglycemia in type 2 diabetes can be alleviated by promoting cellular glucose uptake. Betulinic acid (3β,-3-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic lupane-type triterpenoid compound. Although there have been studies on the antidiabetic activity of betulinic acid, studies on cellular glucose uptake are lacking. We investigated the effects of betulinic acid on glucose uptake and its mechanism of action in 3T3-L1 adipocytes. Betulinic acid significantly stimulated glucose uptake in 3T3-L1 adipocytes by increasing the phosphorylation of the insulin receptor substrate 1-tyrosine (IRS-1tyr) in the insulin signaling pathway, which in turn stimulated the activation of phosphoinositide 3-kinase (PI3K) and the phosphorylation of protein kinase B (Akt). The activation of PI3K and Akt by betulinic acid translocated glucose transporter 4 to the plasma membrane (PM-GLUT4), thereby increasing the expression of PM-GLUT4 and thus stimulating cellular glucose uptake. Betulinic acid also significantly increased the phosphorylation/activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. The activation of PI3K and AMPK by betulinic acid was confirmed using the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. The increase in glucose uptake induced by betulinic acid was significantly decreased by wortmannin and compound C in the 3T3-L1 adipocytes. These results suggest that betulinic acid stimulates glucose uptake by activating PI3K and AMPK in 3T3-L1 adipocytes.

• Journal of Life Science
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• v.18 no.7
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• pp.1005-1010
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• 2008

In this study, we investigated the inhibitory effect of four solvent fractions of Alnus firma on ${\alpha}-amylase$, ${\alpha}-glucosidase$ and aldose reductase activities. The inhibitory test showed that methanol (MeOH) extract and hexane (HX) fraction strongly inhibited pork pancreatin and salivary ${\alpha}-amylase$ activity. The MeOH extract and HX fraction of Alnus firma at the concentration of 4 mg/ml inhibited more than 70% of pancreatin and salivary ${\alpha}-amylase$ activity. The inhibitory effect of fractions has different specificities against ${\alpha}-amylase$ from pancreatin and salivary. In addition, the MeOH extract and butanol (BuOH) fraction showed the highest inhibitory activity on yeast ${\alpha}-glucosidase$ at values of $IC_{50}$ $137.36\;{\mu}g/ml$ and $115.14\;{\mu}g/ml$ respectively. The MeOH extract and BuOH fraction showed the highest inhibitory activity on yeast ${\alpha}-glucosidase$ than commercial agent such as 1-deoxynorjirimycin and acarbose. Inhibition kinetics of solvent fractions showed that ${\alpha}-glucosidase$ has been inhibited noncompetitively by the MeOH, EA and BuOH fraction. The aldose reductase from human muscle cell had been inhibited strongly by the MeOH extract and EA fraction at 57.996% and 83.293% at the concentration of $50\;{\mu}g/ml$, respectively. These findings may contribute to biological significance in that ${\alpha}-amylase$, ${\alpha}-glucosidase$ and aldose reductase inhibitory compounds could be used as a functional food and a drug for the symptomatic treatment of antidiabetic disease in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.8
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• pp.1086-1093
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• 2012

The hypoglycemic and hypolipidemic effects of autoclaved soy flour and DJI chungkukjang powder fermented using Bacillus subtilis DJI were investigated in type 2 diabetic animal models. After a 2-week adaptation period, the diabetic animal model db/db mice were divided into the diabetic control group (D-C group), a diabetic group fed with soybean (D-S group), and a diabetic group fed with DJI chungkukjang (D-CJ group). The body weight gain, food intake, water intake, liver, and adipose tissue weights were not significantly different between the experimental groups. The supplementation of DJI chungkukjang or autoclaved soy flour diet induced a marked reduction of fasting blood glucose, blood glycosylated hemoglobin levels, and glucose levels in the oral glucose tolerance test and AUC for glucose compared with the diabetic control group. However, DJI chungkukjang showed a much stronger antidiabetic effect than unfermented autoclaved soy flour. Serum insulin levels were the same among the groups. The supplementation of DJI chungkukjang or autoclaved soy flour diet also significantly lowered the serum triglyceride, total cholesterol, and LDL-cholesterol levels compared with the control diabetic group, while it elevated the HDL-cholesterol level in the serum. This data suggests that the dietary supplementation of autoclaved soy flour or DJI chungkukjang may be useful in the control of blood glucose in animals with type 2 diabetes.

• Journal of Life Science
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• v.27 no.2
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• pp.155-163
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• 2017

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.257-267
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• 2017

Background: Heat-processed ginseng, sun ginseng (SG), has been reported to have improved therapeutic properties compared with raw forms, such as increased antidiabetic, anti-inflammatory, and antihyperglycemic effects. The aim of this study was to investigate the antiobesity effects of SG through the suppression of cell differentiation and proliferation of mouse 3T3-L1 preadipocyte cells and the lipid accumulation in Caenorhabditis elegans. Methods: To investigate the effect of SG on adipocyte differentiation, levels of stained intracellular lipid droplets were quantified by measuring the oil red O signal in the lipid extracts of cells on differentiation Day 7. To study the effect of SG on fat accumulation in C. elegans, L4 stage worms were cultured on an Escherichia coli OP50 diet supplemented with $10{\mu}g/mL$ of SG, followed by Nile red staining. To determine the effect of SG on gene expression of lipid and glucose metabolism-regulation molecules, messenger RNA (mRNA) levels of genes were analyzed by real-time reverse transcription-polymerase chain reaction analysis. In addition, the phosphorylation of Akt was examined by Western blotting. Results: SG suppressed the differentiation of 3T3-L1 cells stimulated by a mixture of 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI), and inhibited the proliferation of adipocytes during differentiation. Treatment of C. elegans with SG showed reductions in lipid accumulation by Nile red staining, thus directly demonstrating an antiobesity effect for SG. Furthermore, SG treatment down-regulated mRNA and protein expression levels of peroxisome proliferator-activated receptor subtype ${\gamma}$ ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein-alpha ($C/EBP{\alpha}$) and decreased the mRNA level of sterol regulatory element-binding protein 1c in MDI-treated adipocytes in a dose-dependent manner. In differentiated 3T3-L1 cells, mRNA expression levels of lipid metabolism-regulating factors, such as amplifying mouse fatty acid-binding protein 2, leptin, lipoprotein lipase, fatty acid transporter protein 1, fatty acid synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were increased, whereas that of the lipolytic enzyme carnitine palmitoyltransferase-1 was decreased. Our data demonstrate that SG inversely regulated the expression of these genes in differentiated adipocytes. SG induced increases in the mRNA expression of glycolytic enzymes such as glucokinase and pyruvate kinase, and a decrease in the mRNA level of the glycogenic enzyme phosphoenol pyruvate carboxylase. In addition, mRNA levels of the glucose transporters GLUT1, GLUT4, and insulin receptor substrate-1 were elevated by MDI stimulation, whereas SG dose-dependently inhibited the expression of these genes in differentiated adipocytes. SG also inhibited the phosphorylation of Akt (Ser473) at an early phase of MDI stimulation. Intracellular nitric oxide (NO) production and endothelial nitric oxide synthase mRNA levels were markedly decreased by MDI stimulation and recovered by SG treatment of adipocytes. Conclusion: Our results suggest that SG effectively inhibits adipocyte proliferation and differentiation through the downregulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$, by suppressing Akt (Ser473) phosphorylation and enhancing NO production. These results provide strong evidence to support the development of SG for antiobesity treatment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.6
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• pp.1026-1038
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• 1995

Although aloe lost a lot of its previous popularity in modern clinical uses as medicine numerous scientific researches still have claimed the beneficial properties(curing and general tonic effect) of aloe gel. Whereas considerable contradictory reports have helped to confuse the aloe gel issue and continually aroused controversy about aloe gel efficacy. However health food, cosmetic and medicinal products made from aloe gel are widely available in the world market especially in U.S.A. so the growing of Aloe plant and the processing of A. vera gel have become big industries in some countries. In some previous papers the salicylic acid, one of the common trace gel components, was thought to have an analgetic and antinflammatory effect. Large amount of Mg ion in the gel was suggested to act as anesthetic, Mg-lactate as antihistamic, and Aloctin A(a glycoprotein) as wound healer by promoting the cell growth. The carboxypeptidase and bradykinase activity in the gel were proposed to have the pain relieving and antiinflammatory effect. But any of thes etheories concerining the physiological action of the trace gel components has not been demonstrated by modern pharmacology, and failed to be supported by clinical research. It was suggested by some research workers that trace amount of anthraquinone compounds in the gel play an important role to act as false substrate inhibitors for PG and TX production(antiprostanoid effect), by which, they believed, inflammation, burn and frostbite, and infected wound could be healed. This hypothesis has not been substantiated. Butthe suggested antimicrobial action, antidiabetic, and antidotic effect of aloe gel are likely to be attributed to the trace anthraquinone compounds. In a lot of recent experimental reports it has been claimed that aloe gel polysaccharides(acetylglucomannan, acetylmannan, and glycoprotein) have the antimicrobial, antinflammatory, antitumour, and infected wound healing effect by immunoenhancement. It is hoped that these effects will be soon documented in clinical studies, then the controversy on aloe gel beneficial effect will cease. In the 30 days subchronic toxicity test the lowest observed adverse effect level of acemannan(acetylmannan) on dog was 5.0 mg/kg, IP. But the aloe gel is generally agreed to be harmless and non toxic even for the internal use such as health food. In the case of idiosynrasy one must keep the delayed type hypersensitivity reaction of aloe gel in mind. In conclusion it seem to be impossible to simply refuse a lot of evidences made by research workers who have claimed aloe gel's beneficial effects and to deny the fact that there had been long therapeutic histories of Aloe plants.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.12
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• pp.1554-1559
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• 2008

This study was performed to investigate the hypoglycemic effect of single and repeated oral administration of medicinal herbal mixture (AD) in streptozotocin (STZ) induced diabetic rats. Angelica decursiva, Lycium chinense and Adenophora triphylla var. japonica Hara were selected by oral glucose tolerance test (OGTT) and mixed for AD mixture. In an oral glucose tolerance test, the AD inhibited the increase in blood glucose levels at 1 hr and 2 hr and decreased incremental glycemic response area under the curve. In a single administration of AD1 (100 mg/kg) and AD2 (500 mg/kg), significant reductions by 5.3% and 12.3% were observed in fasting blood glucose level for 4 hours. During the 1 month of the experimental period, AD1 and AD2 was given to the STZ induced diabetic rats. At 4th week, the fasting blood glucose levels of AD1 and AD2 caused a fall of 25.5% and 37.9%, respectively. In addition, the body weights were decreased by 7.7% (AD1) and 1.7% (AD2), respectively, compared with diabetic control (DC, decreasing of 10.2%). This study suggests that AD could be potentially useful for fasting and post-prandial hyperglycemia treatment and all these effects concluded to the use of this plant extract to manage diabetes mellitus.

• Journal of Food Hygiene and Safety
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• v.23 no.4
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• pp.297-303
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• 2008

Naringin, major citrus flavonoids, has been identified to exert antioxidative, antidiabetic, and lipid lowering effects. In this study, we examined the effect of 0.2 g/kg, 0.5 g/kg naringin supplementation for 3 times/week for 5 weeks on lipid metabolism and antithrombotic capacity in rat. Eighteen five week-old Sprague Dawley(SD) female rats, which had initial body weights of $246{\pm}9g$, were randomly divided into three groups: Control (non naringin group); Low (0.2 g/kg naringin-supplemented group); High (0.5 g/kg naringin-supplemented group). Three groups of rats were supplemented with three experimental diets for 5 weeks and we investigated antithrombotic capacity before sacrifice. Naringin did not significantly alter the body weight gain, relative organ weight. However, the level of serum triglyceride, serum free fatty acid, serum total lipid and serum glucose levels were significantly lowered compared to those of control. The high group (0.5 g/kg naringin-supplemented group) was showed significantly increased bleeding time compared to control group. These results suggest that naringin supplemental diets reduces the level of hypertension, glycosuria and fatness on the female SD rats, when orally administered below the dosage 0.5 g/kg for 5 weeks.

• Journal of the East Asian Society of Dietary Life
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• v.18 no.6
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• pp.939-948
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• 2008

The effects of goat's beard (Aruncus dioicus var ramtschaticus Hara) ethanol extracts (AD) on the streptozotocin-induced diabetic symptoms and oxidative stress in rats were assessed. Experimental plots were divided into normal controls (NC), diabetes controls (DM), diet with 0.3% AD after diabetes induction (SA), and diet with 0.6% AD after diabetes induction (SB), then fed for 5 weeks. In the SA and SB groups as compared with the DM group, diabetic symptoms including weight loss, increase in feed and water intake, and enlargement of the liver and kidney were improved. The levels of blood glucose and serum fructosamine were reduced by $17.9{\sim}27.2%$ and $25.6{\sim}32.6%$, respectively. The activities of alanine aminotransferase, aspartate aminotransferase and the levels of triglycerides, total cholesterol, and LDL-cholesterol in the serum were reduced by $25.6{\sim}30.3$, $42.37{\sim}55.51$, $26.85{\sim}30.44$ and $37.29{\sim}39.11%$, respectively, whereas the level of HDL-cholesterol was increased by $37.29{\sim}39.11%$. Hepatic total (T) and O type (O) activities of xanthine oxidoreductase, O/T ratio(%) and level of lipid peroxide were significantly decreased, while the level of glutathione was increased, and also the activities of superoxide dismutase and glutathione S-transferase were increased by $56.84{\sim}94.90%$ and $57.14{\sim}68.92%$, respectively. In the above results, it was noted that AD has an antidiabetic effect which alleviated hyperglycemia and the AD reduced and/or prevented the tissue damage caused by diabetes yia the inhibition of reactive oxygen species (ROS) generating systems concurrent with an increase in ROS scavenging.