• Bulletin of the Korean Chemical Society
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• v.29 no.5
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• pp.921-927
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• 2008

Discovery of $\alpha$-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate mediated diseases. As a method for the discovery of new novel inhibitors of $\alpha$-glucosidase, we have addressed the performance of the computer-aided drug design protocol involving the homology modeling of $\alpha$-glucosidase and the structure-based virtual screening with the two docking tools: FlexX and the automated and improved AutoDock implementing the effects of ligand solvation in the scoring function. The homology modeling of $\alpha$-glucosidase from baker’s yeast provides a high-quality 3-D structure enabling the structure-based inhibitor design. Of the two docking programs under consideration, AutoDock is found to be more accurate than FlexX in terms of scoring putative ligands to the extent of 5-fold enhancement of hit rate in database screening when 1% of database coverage is used as a cutoff. A detailed binding mode analysis of the known inhibitors shows that they can be stabilized in the active site of $\alpha$- glucosidase through the simultaneous establishment of the multiple hydrogen bond and hydrophobic interactions. The present study demonstrates the usefulness of the automated AutoDock program with the improved scoring function as a docking tool for virtual screening of new $\alpha$-glucosidase inhibitors as well as for binding mode analysis to elucidate the activities of known inhibitors.

• Korean Journal of Pharmacognosy
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• v.46 no.2
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• pp.105-108
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• 2015

To establish the anti-diabetic(α-glucosidase inhibitory) activity of D. lotus leaf extract, isolate and identify the constituents responsible for the activity. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of ;${\alpha}$-glucosidase, allowed isolation and identification of the active components. Liquid chromatography/mass spectrometry(LC/MS), ¹ H-NMR and ¹³ C-NMR spectra analyses demonstrated that the active compound was myricetin-3-O-;${\alpha}$-L-rhamnoside(1). Compound 1 demonstrated a strong inhibition on the α-glucosidase, in vitro and ;${\alpha}$-glucosidase inhibitory value was calculated as 98.08%, when that of a reference drug, acarbose was estimated as 83.03%. The present study indicates compound 1 could be considered as an ;${\alpha}$-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.

• Applied Biological Chemistry
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• v.48 no.1
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• pp.103-108
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• 2005

${\alpha}-Amylase$ inhibitor is used to control blood glucose level by inhibiting starch digestion in the small intestine and delaying the absorption of glucose. In this study, we investigated the effect of the ethanol extracts from more than 1400 species of plants against ${\alpha}-amylase$ with the aim of developing a new ${\alpha}-amylase$ inhibitor. In the results, Cornus walteri extracts showed the highest inhibition activity. The inhibitory effect of Cornus walteri extract on the carbohydrate hydrolysis enzymes has different sensitivities against ${\alpha}-amylase$ from salivary and pancreatin and against ${\alpha}-glucosidase$ from yeast and porcine small intestine. In the study of inhibition kinetics of ${\alpha}-amylase$ and ${\alpha}-glucosidase$, Cornus walteri extract showed competitive inhibition against salivary and pancreatin while showing the combination of uncompetitive and noncompetitive inhibition against ${\alpha}-glucosidase$. The Cornus walteri extract was stable at acidic and thermal conditions. As for the blood glucose and body weight levels of Cornus walteri extract, we confirmed anti-hyperglycemic and anti-obesity effects. Also, in the investigation of the mRNA lever, Cornus walteri extract upregulated the level of GLUT4 mRNA in the quadriceps muscle.

• Applied Biological Chemistry
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• v.43 no.1
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• pp.12-17
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• 2000

For the enzymatic production of $2-O-{\alpha}-D-glucopyranosyl-L-ascorbic$ acid (AA-2G) from ascorbic acid, rice seed was used as the source of ${\alpha}-glucosidase$ having transglucosylation activity. Among six rice varieties, cultivated in Korea, ${\alpha}-glucosidase$ activity of Oryza savita L. cv. Ilpumbyeo was the highest with 125.03 unit/ml and it had maximum specific activity with 8.52 unit/mg protein when rice seeds were grown for 3 days after germination. For the production of AA-2G using crude extract of O. savita L. cv. Ilpumbyeo, maltose was most effective glucose donor. The optimum concentration of maltose and ascorbic acid were 125 mM and 175 mM, respectively. The optimum concentration of ${\alpha}-glucosidase$ was 100 unit. The most effective buffer was 100 mM sodium citrate. The optimum pH and temperature were 5.0 and $60^{\circ}C$, respectively. Under the optimum condition, $108.43\;{\mu}M/unit$ of AA-2G was produced from ascorbic acid after 35 minutes of reaction, which corresponds to 6.2% of conversion ratio based on the amount of ascorbic acid used.

• Journal of Life Science
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• v.27 no.9
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• pp.1052-1058
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• 2017

Gelidium amansii shows antioxidant and anti-obesity effects; however, the effect on postprandial blood glucose levels is not known. The objective of the present study was to investigate the inhibitory effect of Gelidium amansii extract (GAE) on carbohydrate-digesting enzymes and its ability to alleviate postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Gelidium amansii was extracted with 80% ethanol and concentrated for use in this study. The ${\alpha}-glucosidase$ and ${\alpha}-amylase$ inhibition assays were performed using the colorimetric method. ICR normal and STZ-induced diabetic mice were orally administered GAE (300 mg/kg body weight) or acarbose (100 mg/kg body weight) alone or soluble starch (2 g/kg body weight). Blood samples were taken from the tail vein at 0, 30, 60 and 120 min. Our results indicated that GAE markedly inhibited ${\alpha}-glucosidase$ and ${\alpha}-amylase$ activities with $IC_{50}$ values of $0.099{\pm}0.009mg/ml$ and $0.178{\pm}0.038mg/ml$, respectively, and was a more effective inhibitor than acarbose, the positive control. Further, the postprandial blood glucose levels of STZ-induced diabetic mice in the GAE-administered group were significantly lower than those of control group mice (p<0.05). Moreover, the area under the curves (AUC) significantly decreased with GAE administration in STZ-induced diabetic mice (p<0.05). These results indicate that GAE may be effective in decreasing postprandial blood glucose levels by inhibiting carbohydrate-digesting enzymes such as ${\alpha}-amylase$ and ${\alpha}-glucosidase$. Therefore, GAE could be used as a potential functional food for alleviating postprandial hyperglycemia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.131-135
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• 2002

This study was carried out to investigate the inhibitory effect of extracts from Paeoniae radix on postprandial hyperglycemia. Organic solvent (hexane, ethyl acetate, butanol, water) extracts from Paeoniae radix were fractionated by high performance liquid chromatography. These fractions were used to screen $\alpha$-glucosidase (EC 3.2.1.20) inhibitors by microplate colorimetric assay. The fractions 11, 12, 18, 19 of ethyl acetate extract from Paeoniae radix showed inhibitory activity by 85%, 84%, 77%, 77% at concentration of 20 $\mu\textrm{g}$/mL, respectively. The selected fractions (no. 10~no. 19) significantly reduced by 22% the blood glucose elevation in comparison with positive control in mice loaded with maltose. The fractions of Paeoniae radix were determined in vitro inhibitory activity on $\alpha$-glucosidase and in vivo inhibition effect on blood glucose elevation in mice. Therefore, these results suggest that the extract of Paeoniae radix can be used as a new nutraceutial for inhibition on postprandial hyperglycemia as well as resource pool for lead compounds as a $\alpha$-glucosidase inhibitor.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.481-494
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• 2009

Background : Radix Sophora Flavescentis (SF) is used for the treatment of diabetes mellitus in Traditional Korean Medicine. However, little is known about the effects of Radix Sophora Flavescentis extract (SFE) on the hypoglycemic mechanism. Objective : We performed a series of experiments to verify the effects of SFE on the proliferation of RIN-m5F, the secretion and synthetic processes of insulin with glucose stimulation and inhibition of $\alpha$-glucosidase. Methods : Various amounts of SFE were added to the RIN-m5F cell culture to identify the effects on the cell proliferation, total amounts of insulin secretion, and related gene expression at the molecular level. Also to identify the inhibitory effect on the $\alpha$-glucosidase activities, ${\rho}NPG$ assay was done with various SFE concentrations followed by comparison with control. Results : SFE did not show considerable effects on RIN-m5F cells proliferation, insulin secretion or insulin mRNA expression, whichever phenomena did not depend on the glucose concentration. However, SFE significantly inhibited $\alpha$-glucosidase activity in a dose dependent manner compared to control. Conclusions : This study showed that SFE has potent $\alpha$-glucosidase inhibitory activity. Thus, SF may by used for the improvement of overall glycemic control. Further mechanism studies on the lipid toxicity and oxidation stress of SF seem to be necessary.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.229-232
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• 2009

The ethanol (EtOH) extract of the branches of Cotinus coggygria (Anacardiaceae) exhibited a significant inhibition on the yeast $\alpha$-glucosidase, one of the key enzymes related with diabetes mellitus, in a dose dependent manner, in vitro. The intensive phytochemical survey of the EtOH extract of the species by way of bioactivity-guided fractionation resulted in the isolation of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (1) as an active principle responsible for the inhibition on $\alpha$-glucosidase, together with two related components 2 and 3. Compound 1 demonstrated a strong inhibition on the yeast $\alpha$-glucosidase, in vitro and $IC_{50}$ value was calculated as 0.96 mg/ml, when that of a reference drug, acarbose was estimated as 5.3 mg/ml. On the other hand, other related constituents of the species, 1,2,3,6-tetra-O-galloyl-$\beta$-D-glucose (2) and gallic acid (3) were exhibited relatively poor inhibition upon the yeast $\alpha$-glucosidase, respectively.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.150-154
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• 2009

We examined ethanol extracts prepared from the Korean marine algae belonging to the Sargassaceae family for their inhibitory effects on ${\alpha}$-glucosidase activity and free radicals in vitro. Among five marine algae, the extracts of Sargassum yezoense were found to possess strongly ${\alpha}$-glucosidase inhibition and free radicals scavenging activities. Two compounds were isolated via bioactivity guided isolation and tested for their effects on ${\alpha}$-glucosidase, DPPH, $ABTS^{+}$ and $Photochem^{(R)}$ analysis. Their chemical structures were elucidated by spectral analysis and direct comparison with authentic compounds; their structures were identified as sargaquinoic acid (1) and sargahydroquinoic acid (2). The inhibitory effects of compound 1 and 2 ($IC_{50}$ value:14.2 and 12.8 ${\mu}M$, respectively) on ${\alpha}$-glucosidase were more potent that of deoxynojirimycin as a positive control ($IC_{50}$ value:18.0 ${\mu}M$). All compounds displayed antioxidative activity which was measured by DPPH, $ABTS^{+}$ and $Photochem^{(R)}$ apparatus.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.446-450
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• 2011

As an effort to find a new scaffold for ${\alpha}$-glucosidase inhibition, we have prepared total 11 phenylalkylated piperazine derivatives and tested their ${\alpha}$-glucosidase inhibitory activities. Compounds 8 ($IC_{50}=2.73{\pm}0.075mM$) possessing two 3-methoxyphenethyl group on 1,4-position of piperazine showed comparable potency to acarbose used as reference. But other compounds were inactive to ${\alpha}$-glucosidase. The result indicated that proper substituents on the piperazine can engender ${\alpha}$-glucosidase inhibitory activities on the piperazine derivatives.