• BMB Reports
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• v.31 no.3
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• pp.269-273
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• 1998

The objective of this study was to evaluate the reversal of multi drug resistance of human cell lines by specific inhibitors of ${\alpha}-glycosidase$ and mannosidases that had been reported to be involved in N-linked oligosaccharide processing of glycoproteins. N-methyldeoxynojirimycin, I-deoxynojirimycin, and castanospermine, which were known to be potent inhibitors of both ${\alpha}-glycosidase$ I and II, showed no activity against the multidrug resistant phenotype of the cell lines of SNU1DOX, KB-V1, and MCF-7/ADR. In contrast, I-deoxymannojirimycin, an inhibitor of mannosidase I, resulted in a slight reversal for the vinblastine resistance of the KB-V1 cell line, but did not show any activity toward the other cell lines. Parallel experiments with tunicamycin, an inhibitor of N-linked glycosylation, also resulted in no significant changes in multidrug resistant (MDR) phenotype of the cell lines tested in this work. These observations suggest that the unglycosylation of P-glycoprotein associated with the inhibitor treatments might not be correlated with the reversal of multidrug resistance of the cell lines tested in this study.

• Journal of Sericultural and Entomological Science
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• v.48 no.1
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• pp.25-27
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• 2006

[ ${\alpha}-Glycosidase$ ] inhibitors slows the velocity of the uptake of monosaccharides in the small intestine by retarding the speed of degradation of disaccharides to monosaccharides, which made it possible to develop ${\alpha}-glycosidase$ inhibitors as the antihyperglycemic ('antihyperglycemic' means 'blood-glucose-level-lowering') reagent for the diabetic patients such as acarbose and miglitol. Twenty kinds of ${\alpha}-glycosidase$ inhibitors have been reported to exist in mulberry, Morns alba, and some of them are also found in the silkworm, Bombyx mari, as the result of its daily feeding of mulberry leaves as the sole diet. 1-Deoxynojirimycin (DNJ), one of the most potent ${\alpha}-glycosidase$ inhibitor, is the most abundant among polyhydroxylated alkaloids with ${\alpha}-glycosidase$ inhibiting activity in both M alba and B. mari, therefore considered the antihyperglycemic criterion of the mulberry- or silkworm-based neutroceutical products. DNJ is thought to be accumulated in the body of silkworm because the its concentration in the silkworm body is two to three times as much as that in the mulberry leaves. Eighteen silkworm F1 varieties have been recommended for industrial rearing in Korea by some standards such as pathological strength. DNJ concentration in 18 recommendedwere measured at 3rd day in the 5th instar after lyophilization to determine the varieties that accumulates DNJ in its body most. GeumOk-Jam was the highest in the DNJ concentration of 5.45 mg/gDW among the recommended F1 varieties.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.364-370
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• 1998

Glycosidase inhibitors from urine of Bombyx mori were isolated and their inhibitory activities on glycosidases were evaluated. Six compounds were isolated by using several ion exchange columns, and their chemical structures were identified by the physicochemical and spectral data. Compound IV, V and Ⅵ were identified as 1-deoxynojirimycin, fagomine and 1,4-dideoxy-1,4-imino-D-arabinitol, respectively. Among six compounds isolated,1-deoxynojirimycin(IV) was the most potent inhibitor on $\alpha$-glucosidase and $\beta$-galactosidase of rat intestine, and its inhibitory activities for trehalase and almond $\beta$-glucosidase were relatively weak. Compound V and Ⅵl retained a little inhibitory potency toward $\alpha$-glucosidase and $\beta$-galactosidase. Compound II and III, however, have been found to have no effect on all glycosidases tested in this study.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.242-246
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• 1998

The inhibitory activities of Amberlite active fraction, which was obtained from methanol soluble fraction of freeze dried slikworm urine, on the rat intestinal glycosidase-catalyzed enzymatic reaction were examined in in viro and in vivo experiments. Amberlite active fraction showed significant inhibitory effects on the hydrolysis of o-glycosidic bond, especially $\alpha$-1,4 bond. On the other hand, the inhibition on the hydrolysis of $\beta$-glycosidic bond was very weak. Oral administration of Amberlite active fraction resulted in a dose-dependent decrease in the blood glucose after an oral maltose load, and postprandial hyperglycemia in carbohydrate-loaded mice was suppressed by Amberlite active fraction at 60 mgHg in decreasing order of maltose, starch, sucrose and lactose. 60 mg/kg of Amberlite active fraction lowered the blood glucose level markedly after 18, 35, and 60 min after an oral maltose load and the antihyperglycemic activity was maintained upto 90 min. In alloxan-induced hyperglycemic mice, Amberlite active fraction at a dose of 100 mg/kg also significantly lowered blood glucose after an oral maltose load, and its efficacy was almost equivalent to that of acarbowe.

• Bulletin of the Korean Chemical Society
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• v.18 no.11
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• pp.1192-1195
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• 1997

A divergent approach to 2-(hydroxymethyl)pyrrolidine-3,4-diols has been studied with 1,4-dideoxy-1,4-imino-D-arabinitol (D-AB1), a potent glycosidase inhibitor. D-AB1 was efficiently synthesized from 2,3-epoxyalcohol 6a in overall 11% yield.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.115-115
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• 2003

Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated pyrrolidines, piperidines, indolizidines. pyrrolizidine, and nortropanes. Glycosidase are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugate. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indrect inhibition of glycosidases.

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.346-350
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• 1997

The synthesis of cis- and trans-1,6-dihydroxypyrrolizidine starting from trans-4-hydroxy-L-proline and their evaluation as glycosidase inhibitors are reported. The cis-isomer was found to be a potent inhibitor against .alpha.-glucosidase and showed weak inhibitory effect against other glycosidases. The trans-isomer exhibited weak inhibitions of b-glucosidase and amylo-glucosidase and poor inhibition of other glycosidases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.134-134
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• 1998

The modulation of glycosidase activity by inhibitors is of great interest. Such compounds have been shown to be important tools in mechanistic studies on glycohydrolase as well as having promising therapeutic application. An ${\alpha}$-glucosidase inhibitor was isolated from culture filterates of Penicillium sp. The inhibitor was active against ${\alpha}$-glucosidase isolated from yeast and porcine small intestine. However, it showed no inhibition to Aspergillus ${\alpha}$-galactosidase, Escherichia coli ${\beta}$-galactosidase, and jack bean ${\alpha}$-mannosidase. The inhibitor was highly soluble in ether, methanol and chloroform. The inhibitor was purified using silica gel, Sephadex LH-20 column chromatography and reverse-phase HPLC. The inhibitory compound designated PA-7(IC$\sub$50/=35$\mu\textrm{g}$) was obtained as white powder. The structure of PA-7 was determined with spectroscopic data of EI-MS, FAB-MS, $^1$H, and $\^$13/C NMR. The inhibitor has a diketopiperazine moiety.

• International Journal of Industrial Entomology and Biomaterials
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• v.7 no.2
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• pp.161-164
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• 2003

Several polyhydroxylated alkaloids were isolated from the extracts of freeze-dried silkworm powder, and purified by ion exchange chromatographic analysis. Through the HPLC analysis, we could identify 1-deoxynojirimycin (DNJ) and a kind of calystegin $B_2$ (HS-58) as well as a noble compound (HS-74) from the purified polyhydroxylated alkaloids. In order to know the characteristics of these isolated alkaloids as enzyme inhibitors, glycosidase inhibition activities of these identified alkaloids including other two non-purified alkaloids (SWP 3-1 and SWP 3-2) were investigated.

• Journal of the East Asian Society of Dietary Life
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• v.12 no.5
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• pp.364-369
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• 2002

Mulberry leaves are believed to be a potent inhibitor of intestinal $\alpha$-glycosidase and the digestion of sucrose in the small intestine. Mulberry leaves are also blown to help prevent the postprandial hyperglycemia. The objective of this study was to elucidate the functionality and anti-hyperglycemic effect of mulberry leaves, and to develop a functional drink using mulberry leaf, silk peptide and oriental medicine. Several mixtures of mulberry lear extract silk peptide and oriental medicine were made for the purpose of manufacture and formulation of products. These mixtures were tested to check the $\alpha$-glycosidase inhibition effect to find the best formula. The optimum conditions for a mulberry leaf hot water extract were that the size of leaf was under 3mm, the amount of leaf needed 50~100 g/L, extraction temperature 9$0^{\circ}C$ and extraction time 2 hr. The yield of extraction was 20~25%. The anti-hyperglycemic effect of mulberry leaves was at maximum when the concentrations of mulberry leaf extract and silk peptide were 1% and 0.1%, respectively.