Carbohydrate hydrolyzing enzyme
The primary targets of α-glucosidase are its substrates, which include maltose, sucrose, and other α-glucosides. The enzyme catalyzes the hydrolysis of terminal α-1,4-linked glucose residues from the non-reducing end of carbohydrates. By breaking down these substrates, α-glucosidase plays a critical role in carbohydrate digestion and metabolism. The enzyme is also a target for inhibitors that are used to treat diabetes, as they slow down glucose absorption.

α-Glucosidase (α-d-glucoside glucohydrolase) is an exo-type carbohydrase distributed widely in microorganisms, plants, and animal tissues, which catalyzes the liberation of α-glucose from the non reducing end of the substrate. Inhibiting this enzyme slows the elevation of blood sugar following a carbohydrate meal. It is a membrane bound enzyme present in the epithelium of the small intestine, which works to facilitate the absorption of glucose by the small intestine by catalyzing the hydrolytic cleavage of oligosaccharides into absorbable [Figure 1] monosaccharides.[1]
By the inhibition of α-glucosidase in the intestine, the rate of hydrolytic cleavage of oligosaccharide is decreased and the process of carbohydrate digestion spreads to the lower part of small intestine. This spreading of digestion process delays the overall absorption rate of glucose into the blood. This has proved to be one of the best strategies to decrease the postprandial rise in blood glucose and in turn help avoiding the onset of late diabetic complications. [1]
There are reports of the presence of α-glucosidase inhibitors, such as acarbose andvoglibose, in microorganisms, and nojirimycin and 1-deoxynojirimycin in plants, as well as the effects of α-glucosidase inhibitor in wheat kernels on blood glucose levels after food uptake. [1]
α-Glucosidase inhibitory potency of plant extracts and isolated compounds from different origins are discussed in Table 1. [1]

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In vitro, α-glucosidase activity is typically measured using chromogenic or fluorogenic substrates. One common substrate is 4-nitrophenyl-α-D-glucopyranoside, which releases 4-nitrophenol upon hydrolysis, producing a yellow color that can be measured spectrophotometrically at 400 nm. The enzyme is also used to determine the inhibition of glycosidases. α-Glucosidase activity can be quantified using colorimetric microplate assay kits with a detection range of 10 µmol/L to 1000 µmol/L.

α-Glucosidase is an enzyme that is membrane-bound and found in the epithelial cells of the small intestine. It facilitates the hydrolytic breakdown of oligosaccharides into forms that may be absorbed by the small intestine. After carbohydrate meals, the rise in blood glucose is slowed down by inhibiting α-glucosidase [1].

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In vivo, α-glucosidase plays a critical role in carbohydrate digestion in the small intestine. It breaks down disaccharides and oligosaccharides into monosaccharides, which are then absorbed into the bloodstream. Inhibitors of α-glucosidase are used clinically to treat type 2 diabetes by delaying the absorption of glucose and reducing postprandial blood glucose levels. The enzyme's activity is also important in other physiological processes, such as glycogen metabolism.

The in vitro enzyme assay for α-glucosidase typically involves incubating the enzyme with a chromogenic substrate, such as 4-nitrophenyl-α-D-glucopyranoside, in a suitable buffer system. The enzyme hydrolyzes the substrate, releasing 4-nitrophenol, which produces a yellow color. The absorbance is measured at 400 nm, and the activity is calculated based on the rate of 4-nitrophenol release. The assay can be performed in a microplate format for high-throughput screening of inhibitors.

Cellular assays for α-glucosidase typically involve the use of cell lines that express the enzyme, such as intestinal epithelial cells. Cells are lysed, and the lysate is incubated with a chromogenic substrate. The production of the chromophore is measured to quantify enzyme activity. Alternatively, live cells can be used to measure the hydrolysis of fluorogenic substrates that are taken up by the cells. The compound's effects on enzyme activity and cellular metabolism may be assessed.

Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose -0.77%; miglitol -0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08-0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. [2]

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Glycemic control [2]
Compared with placebo, acarbose decreased GHb by 0.77% (95% CI 0.64–0.90) (online appendix A [available at http://care.diabetesjournals.org]) and miglitol by 0.68% (95% CI 0.44–0.93), respectively. For voglibose, only one study was available, which yielded a difference of 0.47% in favor of voglibose (95% CI 0.31–0.63). With respect to GHb, we found no evidence for a dose dependency for acarbose in the range from 50 to 300 mg t.i.d.. The subgroup analyses for acarbose 50, 100, 200, and 300 mg t.i.d. showed a decrease in GHb of 0.90, 0.76, 0.77, and 0.78%, respectively (online appendix A). In contrast, for miglitol, such a dose dependency seemed to be present; miglitol 25, 50, 100, and 200 mg t.i.d. decreased GHb by 0.46, 0.58, 0.79, and 1.26%, respectively. However, the results from this meta-analysis are based on seven comparisons, of which four were derived from one (multiarm) trial. [2]

In the subgroup analysis and meta-regression analyses, we found a tendency toward a larger effect on GHb of acarbose at higher baseline levels for GHb. The subgroup analyses for studies with baseline GHb <7%, 7–9%, and >9% yielded a decrease in GHb of 0.56% (95% CI 0.36–0.76), 0.78% (95% CI 0.63–0.93), and 0.93% (95% CI 0.53–1.33), respectively. In the meta-regression analysis with the effect on GHb as dependent and baseline GHb as an independent variable, we found a regression coefficient of −0.12 (95% CI −0.26 to 0.03), indicating an extra 0.12% GHb decrease for every 1% higher baseline GHb. [2]

The subgroup analysis for study duration indicated that long-term studies (more than 24 weeks) showed less effect on GHb. The decrease in GHb for studies with a duration of less than 24 weeks, equal to 24 weeks, and more than 24 weeks was 0.77% (95% CI 0.61–0.93), 0.82% (95% CI 0.63–1.01), and 0.53% (95% CI 0.20–0.87), respectively. This was mostly due to the data from the UKPDS (duration 156 weeks), in which a decrease of only 0.19% on GHb was found (95% CI −0.29–0.67). [2]

In the subgroup and meta-regression analyses, we also found that the application of a fixed dosage scheme and the absence of a step-up dosage scheme increased the effect on glycemic control but also increased the occurrence of side effects (data not shown). [2]

For acarbose, fasting blood glucose decreased by 1.09 mmol/l (28 comparisons; 95% CI 0.83–1.36), for miglitol by 0.52 mmol/l (2 comparisons; 95% CI 0.16–0.88), and for voglibose by 0.60 mmol/l (1 comparison; 95% CI 0.23–0.97). One-hour postload glucose decreased by 2.32 mmol/l (acarbose; 22 comparisons; 95% CI 1.92–2.73), 2.70 mmol/l (miglitol; 2 comparisons; 95% CI −0.14 to 5.54), and 2.40 mmol/l (voglibose; 1 comparison; 95% CI 1.83–2.97). In contrast to the outcome for GHb, acarbose showed a dose-dependent decrease of postload glucose. Acarbose 50, 100, 200, and 300 mg t.i.d. reduced postload glucose by 1.63, 2.26, 2.78, and 3.62 mmol/l, respectively (online appendix B). [2]

Data from studies that compared AGI with other blood glucose lowering interventions were scarce. Pooling of results was only possible for the comparison of acarbose with sulfonylurea. The overall comparison of acarbose with sulfonylurea yielded a nonsignificant advantage for sulfonylurea with respect to overall GHb of 0.38% (data not shown; online appendix C). However, seven of the studies in the meta-analyses used unequal comparators, because they compared a fixed dose of acarbose with individually adjusted dosages of sulfonylurea or a usual dose of acarbose with a very low dose of glibenclamide. The results for the subgroup “acarbose 100 mg versus glibenclamide 3.5 mg” were not consistent with the other comparisons. This discrepancy remained unexplained. Leaving this subgroup out of the meta-analysis yielded an overall effect of 0.63% (95% CI 0.26–1.00) in favor of sulfonylurea. In the same comparison, outcomes for the meta-analyses for fasting and 1-h postload blood glucose were 0.69 mmol/l in favor of sulfonylurea (95% CI 0.16–1.23) and 0.10 mmol/l in favor of acarbose (95% CI −0.43 to 0.22). [2]

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In vivo animal studies for α-glucosidase typically involve the use of rodent models to study carbohydrate digestion and glucose absorption. The enzyme's activity can be measured in intestinal tissue homogenates. Inhibitors of α-glucosidase are administered orally, and their effects on postprandial blood glucose levels are assessed. The compound's ability to modulate starch digestion and glucose absorption is evaluated.

As an enzyme, α-glucosidase does not have conventional pharmacokinetic properties like absorption, distribution, metabolism, and excretion (ADME). However, the enzyme's stability and activity can be affected by temperature, pH, and the presence of inhibitors or cofactors. The enzyme is typically stored under appropriate conditions to maintain its activity. For research purposes, the enzyme is supplied as a lyophilized powder or as a solution in buffer.

α-Glucosidase is generally considered non-toxic as a research reagent. The enzyme itself is a naturally occurring protein and does not present significant toxicity concerns in laboratory settings. Standard laboratory safety practices should be followed when handling the enzyme preparation, including the use of personal protective equipment. The enzyme is typically handled as a routine laboratory reagent.

[1]. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev. 2011 Jan;5(9):19-29.

[2]. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2005 Jan;28(1):154-63.

Diabetes mellitus is a common metabolic disease characterized by abnormally high blood glucose levels, which can lead to serious complications such as diabetic neuropathy, retinopathy, and cardiovascular disease. One effective way to treat diabetes (especially non-insulin-dependent diabetes mellitus, NIDDM) and reduce postprandial hyperglycemia is to inhibit the activity of carbohydrate hydrolytic enzymes (such as α-glucosidase and α-amylase) in the digestive organs, thereby delaying glucose absorption. α-glucosidase is a key enzyme catalyzing the final step in the carbohydrate digestion process. Therefore, α-glucosidase inhibitors can delay the release of D-glucose from complex dietary carbohydrates, thereby delaying glucose absorption and ultimately reducing postprandial blood glucose levels and inhibiting postprandial hyperglycemia. In recent years, efforts have been made to find effective α-glucosidase inhibitors from natural sources to develop physiologically functional foods or lead compounds for the treatment of diabetes. Many α-glucosidase inhibitors, such as flavonoids, alkaloids, terpenoids, anthocyanins, glycosides, and phenolic compounds, have been isolated from plants. This review focuses on components with α-glucosidase inhibitory activity isolated from different plants and their IC50 values. [1] Objective: To review the efficacy of alpha-glucosidase inhibitors (AGIs) monotherapy in patients with type 2 diabetes, including mortality, morbidity, glycemic control, insulin levels, lipids, weight, and side effects. Study Design and Methods: We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, ongoing trial databases, and reference lists, and contacted relevant experts and manufacturers. Inclusion criteria were randomized controlled trials lasting at least 12 weeks comparing AGI monotherapy with any intervention and including one of the following outcome measures: mortality, morbidity, glycated hemoglobin (GHb), blood glucose, lipids, insulin levels, weight, or side effects. Two independent reviewers evaluated all abstracts, extracted all data, and assessed study quality. We contacted all authors to clarify data. Continuous data are expressed as weighted mean differences and analyzed using a random-effects model. The potential impact of study characteristics and quality was assessed by sensitivity analysis and meta-regression analysis. Results: This review included 41 studies (30 acarbose studies, 7 miglitol studies, 1 voglibose study, and 3 pooled studies), with limited heterogeneity. We found no evidence of effects on mortality or morbidity. Compared with placebo, glucocorticoid receptor antagonists (AGIs) were beneficial for glycated hemoglobin (GHb) (0.77% reduction with acarbose; 0.68% reduction with miglitol), fasting and postprandial blood glucose, and postprandial insulin levels. At acarbose doses above 50 mg, three times daily, the effect on GHb was the same, but the incidence of side effects increased. Acarbose reduced body mass index (BMI) by 0.17 kg/m² (95% CI 0.08–0.26). None of the AGIs had any effect on blood lipids. Compared with sulfonylureas, AGIs appeared to be worse at glycemic control, but they could reduce fasting and postprandial insulin levels. Comparative data with other drugs were limited. Conclusion: We found no evidence of effects on mortality or morbidity. AGI has significant benefits for glycemic control and postprandial insulin levels, but has no effect on blood lipids. Doses exceeding 50 mg of acarbose three times a day are not required.[2]

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α-Glucosidase (EC 3.2.1.20) is an enzyme belonging to the glycoside hydrolase family that catalyzes the hydrolysis of terminal α-1,4-linked glucose residues from the non-reducing end of carbohydrates. It is also known as acid maltase, glucoinvertase, glucosidosucrase, and maltase-glucoamylase. The enzyme is used in the determination of α-amylase and in the synthesis of various 1'-O-sucrose and 1-O-fructose esters. It is also used to determine the inhibition of glycosidases. α-Glucosidase is typically sourced from yeast.

0

9001-42-7

White to off-white solid powder

α-D-Glucosidase

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 10 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)