An enzyme that hydrolyzes glycosidic bonds between monosaccharide components of a polysaccharide.
About 40 years have passed since the classical glycosidase inhibitor, nojirimycin was discovered from the cultured broth of the Streptomyces species. Since then, over one hundred glycosidase inhibitors have been isolated from plants and micro-organisms. Modifying or blocking biological processes by specific glycosidase inhibitors has revealed the vital functions of glycosidases in living systems. Since enzyme-catalyzed carbohydrate hydrolysis is a biologically widespread process, glycosidase inhibitors have many potential applications as agrochemicals and therapeutic agents. Glycosidases are involved in the biosynthesis of the oligosaccharide chains and quality control mechanisms in the endoplasmic reticulum (ER) of the N-linked glycoproteins. Inhibition of these glycosidases can have profound effects on quality control, maturation, transport, and secretion of glycoproteins and can alter cell-cell or cell-virus recognition processes. This principle is the basis for the potential use of glycosidase inhibitors for viral infection, cancer, and genetic disorders.()
Glycosylation inhibitors arise naturally in plants, fungi, and bacteria, probably as part of a chemical defense strategy against other competing organisms in the same econiche. Other compounds have been synthesized based on the known substrate preferences for a particular enzyme or its X-ray crystal structure. In either case, inhibitors act as leads for producing additional analogs, often with increased activity or altered specificity. Plant alkaloids block glycosylation by inhibiting the processing glycosidases involved in N-glycan formation.
Study on the inhibition of alpha-glucosidase by soyasaponins
Zhong Yao Cai. 2003 Sep;26(9):654-6.
Quan J, Yin X, Jin M, Shen M.
- OBJECTIVE: To study the inhibitory effects of soyasaponins on alpha-glucosidase (EC126.96.36.199). METHODS: Soyasaponins were isolated by ODS column chromatography and high-performance liquid chromatography (HPLC) from hypocotyls of soybean. The inhibitory activities of each component of soyasaponins against alpha-glucosidase were tested by colorimetric method. RESULTS: Soyasaponins showed potent inhibitory activities against alpha-glucosidase. Group B, group E and DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) saponins showed stronger potency, which were non-competitive inhibitors of alpha-glucosidase with IC50 values of 10-40 mumol/L. While group A saponins showed a little lower potency with IC50 values of about 2 mmol/L. CONCLUSION: The results suggest soyasaponins, which exhibit inhibitory effects on alpha-glucosidase, seem physiologically useful for suppressing postprandial hyperglycemia in patients with diabetes mellitus.
Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats
J Ethnopharmacol. 2005 Jun 3;99(2):239-44. Epub 2005 Apr 9. Li Y, Wen S, Kota BP, Peng G, Li GQ, Yamahara J, Roufogalis BD.
- Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. The flowering part of Punica granatum Linn. (Punicaceae) (PGF) has been recommended in Unani literature as a remedy for diabetes. We investigated the effect and action mechanism of a methanolic extract from PGF on hyperglycemia in vivo and in vitro. Oral administration of PGF extract markedly lowered plasma glucose levels in non-fasted Zucker diabetic fatty rats (a genetic model of obesity and type 2 diabetes), whereas it had little effect in the fasted animals, suggesting it affected postprandial hyperglycemia in type 2 diabetes. In support of this conclusion the extract was found to markedly inhibit the increase of plasma glucose levels after sucrose loading, but not after glucose loading in mice, and it had no effect on glucose levels in normal mice. In vitro, PGF extract demonstrated a potent inhibitory effect on alpha-glucosidase activity (IC50: 1.8 microg/ml). The inhibition is dependent on the concentration of enzyme and substrate, as well as on the length of pretreatment with the enzyme. These findings strongly suggest that PGF extract improves postprandial hyperglycemia in type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity.
Inhibition of alpha-glucosidase by aqueous extracts of some potent antidiabetic medicinal herbs
Prep Biochem Biotechnol. 2005;35(1):29-36. Onal S, Timur S, Okutucu B, Zihnioglu F.
- Diabetes mellitus is one of the most prevalant diseases of adults. Agents with alpha-glucosidase inhibitory activity have been useful as oral hypoglycemic drugs for the control of hyperglycemia in patients with type 2; noninsulin-dependent, diabetes mellitus (NIDDM). Investigation of some medicinal herbs: Urtica dioica, Taraxacum officinale, Viscum album, and Myrtus communis with alpha-glucosidase inhibitor activity was conducted to identify a prophylactic effect for diabetes in vitro. All plants showed differing potent alpha-glucosidase inhibitory activity. However, Myrtus communis strongly inhibited the enzyme (IC50 = 38 microg/mL). The inhibitory effect of these plants and some common antidiabetic drugs against the enzyme source (baker's yeast, rabbit liver, and small intestine) were also searched. Approximately all inhibitors used in this study showed quite different inhibitory activities, according to alpha-glucosidase origins. Furthermore, subsequent separation of the active material from Myrtus communis by HPLC showed that only one fraction acted as an a-glucosidase inhibitor.
Effects of a medical food containing an herbal alpha-glucosidase inhibitor on postprandial glycemia and insulinemia in healthy adults
J Am Diet Assoc. 2005 Jan;105(1):65-71.
Heacock PM, Hertzler SR, Williams JA, Wolf BW.
- OBJECTIVE: To determine the effect of different doses of Salacia oblonga extract, an herbal alpha-glucosidase inhibitor, on postprandial glycemic, insulinemic, and breath hydrogen responses in healthy adults. DESIGN: Double-masked, randomized crossover design. INTERVENTION: Subjects, after fasting for 12 hours, consumed four test meals consisting of 480 mL of study beverage (14 g fat, 82 g carbohydrate, and 20 g protein) with 0, 500, 700, or 1,000 mg of S oblonga extract on four separate occasions. Capillary finger-prick plasma glucose and venous serum insulin concentrations were measured at baseline and for 2 hours postprandially. Breath hydrogen excretion was measured at baseline and hourly for 8 hours postprandially. SUBJECTS/SETTING: Thirty-nine healthy, nondiabetic adults (body mass index=23.7+/-0.4, age=25.7+/-0.9 years. STATISTICAL ANALYSES PERFORMED: Repeated-measures analysis of variance was applied to the raw data or data that had been transformed (log, rank) when necessary due to nonnormality. The Tukey-Kramer post hoc test was used for pairwise comparisons. RESULTS: Compared with the control, the 1,000-mg S oblonga extract dose reduced the plasma glucose and serum insulin incremental areas under the curve (0 to 120 minutes postprandial) by 23% ( P =.32) and 29% ( P =.01), respectively. The other doses of S oblonga extract did not impact glycemia or insulinemia. Breath hydrogen excretion increased linearly as the dose of S oblonga extract was advanced. CONCLUSIONS: The presence of S oblonga extract tended to lower postprandial glycemia and significantly reduced the postprandial insulin response. The increase in breath hydrogen excretion suggests a mechanism similar to prescription alpha-glucosidase inhibitors. Future studies of S oblonga extract in patients with diabetes are needed.