Alpha-glucosidase (IC50 = 11 nM)
The effects of Acarbose (1, 2, and 3 μM) on TNF-α-induced VSMC migration and proliferation were dose- and time-dependent. Acarbose (1, 2 and 3 μM) dose-dependently decreased β-galactosidase and Ras expression while increasing p-AMPK expression in A7r5 cells that had been pretreated with TNF-α [2].

The effects of Acarbose (1, 2, and 3 μM) on TNF-α-induced VSMC migration and proliferation were dose- and time-dependent. Acarbose (1, 2 and 3 μM) dose-dependently decreased β-galactosidase and Ras expression while increasing p-AMPK expression in A7r5 cells that had been pretreated with TNF-α [2].

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Acarbose shows inhibitory activity against rat intestinal α-glucosidase in both free and immobilized assay systems. The inhibitory potency differs significantly between free AGH (fAGH) and immobilized AGH (iAGH) systems. For maltase activity, the IC₅₀ of acarbose is 11 mM in the fAGH assay, while in the iAGH assay (blocked with β-alanine) it is 430 mM. For sucrase activity, the IC₅₀ is 890 mM in fAGH and 1200 mM in βAla-iAGH. [3]

In diabetic rats, acarbose (300 mg/60 kg body weight) can lower fasting blood glucose and control glucose tolerance without causing weight loss. DM rats' blood levels of TNF-α and IL6 are dramatically inhibited by acarbose [1]. Neointimal IL-6, TNF-α, and iNOS staining intensity were considerably and dose-dependently reduced by acarbose (2.5 and 5.0 mg/kg), but neointimal p-AMPK staining intensity was dramatically raised. In HCD-fed rabbits with no weight loss, acarbose (2.5 and 5.0 mg/kg) substantially and dose-dependently decreased neointimal Ras and β-galactosidase expression [2].

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In a type 2 diabetic rat model (induced by high-fat diet and low-dose streptozotocin), an 8-week treatment with acarbose (30 mg/kg/day and 60 mg/kg/day) significantly reduced fasting blood glucose levels from week 2 to week 8 compared to the diabetic control group. [4]
In the oral glucose tolerance test (OGTT), treatment with acarbose significantly reduced blood glucose levels at 30, 60, and 120 minutes after glucose administration in diabetic rats. The area under the curve (AUC) for blood glucose was also reduced. [4]
Treatment with acarbose (60 mg/kg/day for 8 weeks) significantly reduced serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in diabetic rats. [4]
Treatment with acarbose (60 mg/kg/day for 8 weeks) significantly altered the expression of specific microRNAs (miRNAs) in the ileum of diabetic rats. miR-10a-5p and miR-664 were upregulated, while miR-541 and miR-135b were downregulated. This miRNA modulation led to the downregulation of their target genes, including Il6, Tnf, and Mapk1, at both mRNA and protein levels in the ileum. [4]
The study suggests that acarbose improves blood glucose control in diabetic rats not only via α-glucosidase inhibition but also through activating miR-10a-5p and miR-664 in the ileum, which subsequently suppresses the expression of proinflammatory cytokines (IL-6, TNF-α) and Mitogen-Activated Protein Kinase 1 (MAPK1), likely through the MAPK signaling pathway. [4]

The inhibitory effects of natural and synthetic inhibitors on the intestinal membrane-bound hydrolase, alpha-glucosidase (AGH), were evaluated by using an immobilized cyanogen bromide-activated Sepharose 4B support. Immobilized AGH (iAGH) inhibition study by synthetic inhibitors (acarbose and voglibose) revealed that the magnitude of inhibition differed from that in the free AGH (fAGH) study: IC50 value of acarbose in iAGH-maltase assay system, 340-430 nM; fAGH, 11 nM. iAGH-maltase inhibition by both inhibitors was influenced by blocking reagents with different functional groups (COOH, OH, CH3, and NH2 groups). On the other hand, significant iAGH-sucrase inhibitory activity was observed only when using the negatively charged support induced by 0.1 M beta-alanine. The Km values obtained in the iAGH assay system were similar to those from the fAGH method. With natural inhibitors, the iAGH-sucrase inhibitory activity of D-Xylose, with in vivo glucose suppression, increased twice compared to that in fAGH. Green tea extract gave almost the same inhibition for both AGH assay systems. [3]

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The inhibitory activity of acarbose against α-glucosidase was evaluated using both free and immobilized enzyme systems. For the immobilized AGH (iAGH) assay, AGH was immobilized onto cyanogen bromide-activated Sepharose 4B support and blocked with β-alanine to introduce carboxyl groups. The iAGH support (10 mg wet gel) was placed in a mini-column, and 1.0 ml of model intestinal fluid containing maltose or sucrose was added. After incubation at 37°C for 30 min (maltase) or 60 min (sucrase), the reaction was stopped by filtration, and liberated glucose was measured. For inhibitory assays, 10 µl of inhibitor solution and 990 µl of substrate solution were added to the iAGH support. The IC₅₀ was defined as the concentration required to inhibit 50% of enzyme activity. [3]
The free AGH (fAGH) inhibitory assay was performed using the same quantity of enzyme (25 µg) as in the iAGH system, with identical substrate concentrations and incubation times. The inhibitory activity was estimated by measuring the difference in glucose release with or without inhibitor. [3]

Cell viability analysis [5]
Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay44. Cells were seeded in 24-well culture plates at a density of 2 × 104 cells/well, incubated for 48 h, treated with acarbose at varying concentrations (0.5, 1.0, 2.0, 3.0, and 5.0 μM) for 24 h; or pre-treated with TNF-α (20 ng/ml) for either 24 h or 48 h to evaluate the dose-dependent effects of acarbose on VSMC growth and viability, cultured with 0.5 mg/ml MTT at 37 °C in a humidified atmosphere of 5% CO2 for another 4 h, and solubilized with isopropanol. The viable cell number varied directly with the concentration of formazan product measured spectrophotometrically at 563 nm.

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Wound healing [5]
A7r5 cells were seeded at a density of 1 × 106 ml in 6-well culture plates and incubated for 48 h. A sterile 100-μl pipette tip was used to make a straight scratch in the cell monolayer in each well45. The non-adhering cells were washed out with PBS, and the remaining cells were treated with TNF-α (0, 10, 20, 50 and 100 ng/ml) at 37 °C in a humidified atmosphere of 5% CO2. Under a 40X lens, images of the linear wound (9 fields per well) were taken at 24 and 48 h. Migrated cells were counted per well and the counts were averaged.

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Western blot analysis [5]
Western blot analysis46 was used to assess the expressions and/or activities of these migration-related proteins and thereby the mechanisms underlying the anti-migratory effects of acarbose on VSMCs. Specific antibodies were used to evaluate the expressions of iNOS, Ras, p-AMPK, AMPKα1/2, and TNF-α and β-galactosidase. After pre-treatment with TNF-α (20 ng/ml) for 24 h, the cells were treated with acarbose (0, 1, 2, and 3 μM) for 24 h and lysed. Cell lysates (50 μg of protein) were separated by electrophoresis on 8–12% SDS polyacrylamide gels and transferred to nitrocellulose membranes. The membranes were incubated with Tris-buffered saline (TBS) containing 1% (w/v) nonfat-milk and 0.1% (v/v) Tween-20 (TBST) for 1 h to block non-specific binding, washed with TBST for 30 min, incubated with the appropriate primary antibody for 2 h, incubated with horseradish peroxidase-conjugated second antibody for 1 h, developed using ECL chemiluminescence, and analyzed by densitometry using AlphaImager Series 2200 software. Compound C (an AMPK inhibitor, 5 μM) and L-NAME (iNOS inhibitor, 0.5 mM) were used to confirm AMPK and iNOS expression in TNF-α-pretreated acarbose-treated (1, 2 and 3 μM for 24 h) cells. Results are representative of at least 3 independent experiments.

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The rat thoracic aorta smooth muscle cell line A7r5 was used. Cells were cultured in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum, L-glutamine, sodium bicarbonate, and penicillin/streptomycin. Before experiments, cells were pre-cultured in medium containing 0.5% fetal bovine serum for 48 hours. [5]
For cell viability assay, A7r5 cells were seeded in 24-well plates, pre-treated with TNF-α (20 ng/ml), and then co-treated with various concentrations of acarbose (0.5 to 5.0 μM) for 24 or 48 hours. Cell viability was determined using the MTT assay, where cells were incubated with MTT reagent and the resulting formazan product was solubilized and measured spectrophotometrically. [5]
For the wound healing (migration) assay, A7r5 cells were seeded in 6-well plates to form a confluent monolayer. A straight scratch was made using a sterile pipette tip. After washing, cells were treated with TNF-α (20 ng/ml) and co-treated with acarbose (0, 1, 2, 3 μM). Images of the wound area were taken at 0, 24, and 48 hours under a microscope, and migrated cells into the denuded zone were counted. [5]
For protein expression analysis, A7r5 cells were pre-treated with TNF-α (20 ng/ml) for 24 hours, then treated with acarbose (0, 1, 2, 3 μM) for an additional 24 hours. Cells were lysed, and proteins were separated by SDS-PAGE, transferred to membranes, and probed with specific primary antibodies (e.g., iNOS, Ras, p-AMPK, β-galactosidase) and corresponding secondary antibodies. Signals were detected using chemiluminescence. [5]
To investigate mechanism, cells were pre-treated with TNF-α, then co-treated with acarbose (3 μM) in the presence or absence of the AMPK inhibitor Compound C (5 μM) or the iNOS inhibitor L-NAME (0.5 mM) for 30 minutes prior to acarbose treatment. Protein expression was then analyzed by Western blot. [5]

Animal Models, Grouping, and Treatment [4]
\nMale Sprague-Dawley rats (280–320 g) were used. As previously described, diabetic rats were fed a high-fat diet (40% of calories as fat) for 4 weeks, and then were administered a single dose of streptozotocin (STZ, 50 mg/kg, tail vein) formulated in 0.1 mmol/L citrate buffer, pH 4.5. One week after the STZ injection, the random blood glucose level of the diabetic rats was measured to confirm hyperglycemia. Random blood glucose above 16.7 mmol/L was used to define rats as diabetic. Diabetic rats were fed a high-fat diet throughout the experiment. Diabetic rats with a similar degree of hyperglycemia were randomly divided into three groups: vehicle, low dose acarbose (AcarL), and high dose acarbose (AcarH) groups (n = 10, in each group). The typical human daily dose of acarbose is 300 mg/60 kg body weight. According to the formula: drat = dhuman × 0.71/0.11, the corresponding dose of acarbose for rats is 32.28 mg/kg per day. Therefore, we selected 30 and 60 mg/kg per day as low and high dosages, respectively. The control (n = 10) and the diabetic group received 0.5% saline, whereas the AcarL and AcarH groups were given acarbose at doses of 30 and 60 mg/kg in a 0.5% saline solution, respectively. The drug was administered once daily for 8 weeks using a gastric gavage. All animals were housed in an environmentally controlled room at 25°C with a 12 h light-dark cycles and were given free access to food and water throughout the experimental period. Fasting animals were allowed free access to water. After 6 weeks of treatment, an oral glucose tolerance test (OGTT) was performed. After 8 weeks of treatment, blood samples were taken from rats after anesthesia. The rats were then sacrificed. Some terminal ileums were collected for performing the microarray and quantitative real-time reverse transcription PCR (qRT-PCR) analysis. Other terminal ileums were fixed in 10% neutralized formalin for immunohistochemical staining. \n

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\nAnimals and diets [5]
\nTwenty-four male New Zealand white rabbits, weighing 2500 g were used. They were individually housed in metal cages in an air-conditioned room (22 ± 2 °C, 55 ± 5% humidity), under a 12 h light/12 h dark cycle with free access to food and water. All rabbits were randomly assigned to four groups of 6 animals each and were fed either standard chow (Group I), high cholesterol diet (HCD; containing 95.7% standard Purina chow + 3% lard oil + 0.5% cholesterol) (Group II), HCD diet and 2.5 mg kg−1 per day acarbose (Group III), or HCD diet and 5.0 mg kg−1 per day acarbose (Group IV). At the end of the 25 weeks, all rabbits were sacrificed by exsanguination under deep anesthesia with pentobarbital (30 mg kg−1 i.v.) injected via the marginal ear vein. Serum was stored at −80 °C prior to measurement of serum values. The aortic arch and thoracic aortas were carefully removed to protect the endothelial lining, and were collected and freed of adhering soft tissue.

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\nA rat model of type 2 diabetes was established by feeding male Sprague-Dawley rats a high-fat diet for 4 weeks, followed by a single tail vein injection of streptozotocin (50 mg/kg) in citrate buffer. Rats with random blood glucose levels above 16.7 mmol/L one week later were considered diabetic. [4]
\nDiabetic rats were randomly divided into groups: a diabetic control group (DM), a low-dose acarbose group (AcarL, 30 mg/kg/day), and a high-dose acarbose group (AcarH, 60 mg/kg/day). A separate group of non-diabetic rats served as the normal control. The drug was administered once daily for 8 weeks via oral gavage. Acarbose was dissolved in 0.5% saline. The control and DM groups received an equal volume of 0.5% saline. [4]
\nBody weight and 6-hour fasting blood glucose (measured from tail vein blood) were monitored every 2 weeks. [4]
\nAn oral glucose tolerance test (OGTT) was performed after 6 weeks of treatment. Rats were fasted for 6 hours, then orally administered glucose at 2.2 g/kg. Blood glucose levels were measured from tail veins at 0, 30, 60, and 120 minutes after glucose administration. [4]
\nAfter 8 weeks of treatment, rats were anesthetized, blood samples were collected for serum analysis, and then they were sacrificed. Terminal ileum tissues were collected. Some were snap-frozen for RNA extraction (microarray and qPCR analysis), and others were fixed in 10% neutral buffered formalin for immunohistochemical staining. [4]

Absorption, Distribution and Excretion
Acarbose has extremely low oral bioavailability; less than 1-2% of the original drug enters the systemic circulation after oral administration. Nevertheless, after oral administration of radiolabeled acarbose, approximately 35% of the total radioactivity enters the systemic circulation, with peak plasma radioactivity occurring 14-24 hours after administration—this delay likely reflects the absorption of metabolites rather than the original drug. Because acarbose is intended to act in the intestines, its extremely low oral bioavailability is ideal for therapeutic purposes. Approximately half of the oral dose is excreted in the feces within 96 hours of administration. A small amount of the drug substance (approximately 34% of the oral dose) is absorbed into the systemic circulation and is primarily excreted by the kidneys. This suggests that renal excretion would be an important clearance route if the original drug were more readily absorbed—a view supported by further data: after intravenous administration of acarbose, approximately 89% of the drug is excreted in the urine in its active form (compared to less than 2% after oral administration), with excretion occurring within 48 hours. In a study of six healthy men, less than 2% of the active drug was absorbed after oral administration of acarbose, compared to approximately 35% of the total radioactivity of the 14C-labeled oral dose. On average, 51% of the oral dose was excreted in feces within 96 hours as unabsorbed drug-associated radioactive material. The low systemic bioavailability of acarbose, due to its local action in the gastrointestinal tract, is ideal for therapeutic use. In healthy volunteers, peak plasma concentrations of radioactive material were reached 14–24 hours after oral administration of 14C-labeled acarbose, while peak plasma concentrations of the active drug were reached in approximately 1 hour. The delayed absorption of acarbose-associated radioactive material reflects the absorption of metabolites produced by intestinal bacteria or enzymes. Acarbose is metabolized entirely in the gastrointestinal tract, primarily by intestinal bacteria, but also by digestive enzymes. A portion of these metabolites (approximately 34% of the dose) are absorbed and excreted in the urine.
Acarbose absorbed in its intact drug form is almost entirely excreted by the kidneys. Following intravenous administration of acarbose, 89% of the active drug is recovered in the urine within 48 hours. In contrast, less than 2% of the active drug (i.e., the parent compound and active metabolites) is recovered in the urine after oral administration. This is consistent with the low bioavailability of the parent drug.
For more complete data on absorption, distribution, and excretion of acarbose (6 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Acarbose is extensively metabolized in the gastrointestinal tract, primarily by intestinal bacteria and to a lesser extent by digestive enzymes, producing at least 13 identified metabolites. Approximately one-third of these metabolites are absorbed into the bloodstream and subsequently excreted by the kidneys. The major metabolites appear to be methyl, sulfate, and glucuronide conjugates of 4-methylpyrophenol. Only one metabolite—produced by the cleavage of glucose molecules from acarbose—has been identified as having α-glucosidase inhibitory activity. Acarbose is primarily metabolized in the gastrointestinal tract, mainly by intestinal bacteria, but also by digestive enzymes. At least 13 metabolites have been isolated from urine samples by chromatography. The major metabolite has been identified as a 4-methylpyrophenol derivative (i.e., a sulfate, methyl, and glucuronide conjugate). One of the metabolites (formed by the cleavage of glucose molecules from acarbose) also exhibits α-glucosidase inhibitory activity. This metabolite and its parent compound are recovered from urine, representing less than 2% of the total administered dose.
Biological Half-Life
In healthy volunteers, the plasma elimination half-life of acarbose is approximately 2 hours.

Hepatotoxicity
In several large clinical trials, the incidence (2% to 5%) of serum enzyme elevations exceeding three times the upper limit of normal in the acarbose treatment group was higher than in the placebo group, but all elevations were asymptomatic and returned to normal rapidly after discontinuation of the drug. These studies did not report any clinically significant liver injury cases. However, since the approval and widespread clinical use of acarbose, at least a dozen clinically significant liver injury cases have been associated with its use. Liver injury typically appears 2 to 8 months after the start of treatment and is accompanied by hepatocellular serum enzyme elevations and significantly elevated serum ALT levels, suggesting acute viral hepatitis. Immune hypersensitivity features and autoantibody formation are atypical. While most cases are mild, some cases are accompanied by significant jaundice, and the sponsor has received reports of deaths. Currently, there are no cases of chronic liver injury or bile duct disappearance syndrome associated with acarbose use, and most large case series of drug-induced liver injury and acute liver failure studies have not identified acarbose-induced cases. Rechallenge tests were performed in several cases, showing recurrence, but with shortened onset time.
Probability Score: B (Rare but likely a clinically significant cause of liver injury).
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
Since less than 2% of the acarbose dose is absorbed by the mother's gastrointestinal tract, the drug is unlikely to be passed to the infant through breast milk.
◉ Effects on Breastfed Infants
No relevant published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information found as of the revision date.
Protein Binding
Since only 1-2% of the oral dose is absorbed into the bloodstream, acarbose is unlikely to bind to clinically significant proteins.
Interactions
…There are reports of possible interactions between digoxin and acarbose. These reports indicate that co-administration of acarbose with digoxin significantly reduces the absorption of digoxin. Acarbose's hypoglycemic effect stems from its reversible competitive inhibition of α-glucosidase, an enzyme that hydrolyzes oligosaccharides, which are subsequently absorbed as glucose molecules. Acarbose primarily exerts its effects in the intestines, with the majority being excreted unchanged in feces. Digoxin is a commonly used medication for treating heart failure and/or chronic atrial fibrillation. Acarbose slows the digestion of sucrose and starch; therefore, it can lead to gastrointestinal motility disorders and loose stools. Thus, the combined use of acarbose and digoxin may increase gastrointestinal motility, thereby reducing digoxin absorption. Acarbose may also interfere with the pre-absorption hydrolysis of digoxin, altering the release of corresponding digoxin metabolites and affecting the reliability of digoxin laboratory tests. These case reports indicate that acarbose reduces digoxin absorption. ...
In a single-center, placebo-controlled clinical study, researchers tested the pharmacodynamic effects of an antacid containing magnesium hydroxide and aluminum hydroxide (Maalox 70; 10 mL) on the oral hypoglycemic agent acarbose (Glucobay 100, Bay g 5421, CAS 56180; 100 mg) in 24 healthy male volunteers. The drugs were used alone or in combination and compared with placebo. Volunteers were randomized to four different treatment groups. The daily dosing regimen for 4 days was: one placebo tablet, or one tablet containing 100 mg of acarbose, or one tablet containing 100 mg of acarbose plus 10 mL of antacid suspension, or one placebo plus 10 mL of antacid suspension. A washout period of 6–10 days was provided between each group. Efficacy was assessed based on postprandial blood glucose and serum insulin levels (after 75 g sucrose intake) and expressed as maximum concentration and area under the curve (0–4 hours). No effect was detected on the blood glucose and insulin-lowering effects of antacids on acarbose. Therefore, there appears to be no significant interaction between acarbose and the tested antacids. Drugs similar to the tested antacids should not be listed as contraindications when used in combination with acarbose. This study aimed to investigate whether acarbose treatment altered the pharmacokinetics (PK) of concurrently administered rosiglitazone. Sixteen healthy volunteers (24–59 years of age) received a single 8 mg dose of rosiglitazone on day 1, followed by repeated administration of acarbose [100 mg three times daily with meals] for 7 consecutive days. On the last day of the three-times-daily acarbose administration (day 8), a single rosiglitazone dose was administered concurrently with the morning acarbose dose. PK curves after rosiglitazone administration on days 1 and 8 were compared, and point estimates (PE) and their 95% confidence intervals (CI) were calculated. Acarbose has no effect on the absorption of rosiglitazone (measured by peak plasma concentration (Cmax) and time to peak concentration (Tmax)). During co-administration of rosiglitazone and acarbose, the area under the concentration-time curve (AUC_0-∞) decreased by an average of 12% (95% CI -21%, -2%), while the terminal elimination half-life was shortened by approximately 1 hour (23%) (4.9 hours vs. 3.8 hours). This slight decrease in AUC_0-∞ appears to be due to changes in the systemic clearance of rosiglitazone, rather than changes in absorption. These observed changes in AUC_0-∞ and half-life may not be clinically significant. Co-administration of rosiglitazone and acarbose is well tolerated. Administration of acarbose at therapeutic doses has a small, but clinically insignificant, effect on the pharmacokinetics of rosiglitazone.

[1]. A review of the safety and efficacy of acarbose in diabetes mellitus. Pharmacotherapy. 1996;16(5):792-805.

[2]. Acarbose: oral anti-diabetes drug with additional cardiovascular benefits [published correction appears in Expert Rev Cardiovasc Ther. 2009 Mar;7(3):330]. Expert Rev Cardiovasc Ther. 2008;6(2):153-163.

[3]. Evaluation of alpha-glucosidase inhibition by using an immobilized assay system. Biol Pharm Bull. 2000;23(9):1084-1087.

[4]. Acarbose Reduces Blood Glucose by Activating miR-10a-5p and miR-664 in Diabetic Rats. PLoS One. 2013 Nov 18;8(11):e79697.

[5]. Pleiotropic effects of acarbose on atherosclerosis development in rabbits are mediated via upregulating AMPK signals. Sci Rep. 2016 Dec 7;6:3864.

(2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohexyl-2-enyl]amino]-2-oxacyclohexyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxacyclohexyl]oxy]-6-(hydroxymethyl)oxacyclohexane-2,3,4-triol is a glycoside and aminocyclool. Acarbose is a complex oligosaccharide that inhibits various enzymes in the gut responsible for breaking down complex carbohydrates. Acarbose inhibits pancreatic α-amylase and membrane-bound α-glucosidases (including intestinal glucosidase, sucrase, maltase, and isomaltase), enzymes responsible for metabolizing complex starches, oligosaccharides, trisaccharides, and disaccharides, into absorbable monosaccharides. By inhibiting the activity of these enzymes, acarbose limits the absorption of dietary carbohydrates, thereby reducing postprandial blood glucose and insulin levels. Therefore, acarbose is often used in combination with diet, exercise, and other pharmacological therapies to control blood glucose levels in patients with type 2 diabetes. Acarbose is one of only two currently approved α-glucosidase inhibitors (the other being miglitol), first approved by the FDA in 1995 under the brand name Precose (now discontinued). Due to the relatively small effect of this type of antidiabetic drug on glycated hemoglobin (A1c), the need for three-times daily dosing, and the potential for significant gastrointestinal adverse reactions, it has not been widely used. Acarbose is an α-glucosidase inhibitor that reduces intestinal absorption of carbohydrates and is used as adjunctive therapy in the treatment of type 2 diabetes. Acarbose has been associated with rare, clinically significant cases of acute liver injury. It has been reported as an early-maturing sugar in Hintonia latiflora, Hericium erinaceus, and Xylaria feejeensis, with supporting data. Acarbose is a pseudotetrasaccharide that inhibits α-glucosidase and pancreatic α-amylase, exhibiting hypoglycemic activity. Acarbose binds to and inhibits α-glucosidase, an intestinal enzyme located at the brush border of the small intestine that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. This prevents the breakdown of larger carbohydrates into glucose, thus reducing the postprandial rise in blood glucose levels. Furthermore, acarbose inhibits pancreatic α-amylase, which hydrolyzes complex starches into oligosaccharides in the small intestine. Acarbose is an α-glucosidase inhibitor that slows the digestion and absorption of dietary carbohydrates in the small intestine. See also: Acarbose (note moved to). Drug Indications Acarbose is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. FDA Label Mechanism of Action Alpha-glucosidases, located at the brush border of the intestinal mucosa, metabolize oligosaccharides, trisaccharides, and disaccharides (e.g., sucrose) into smaller, more readily absorbed monosaccharides (e.g., glucose, fructose). These drugs work synergistically with pancreatic alpha-amylase, an enzyme present in the intestinal lumen that hydrolyzes complex starches into oligosaccharides. Acarbose is a complex oligosaccharide that competitively and reversibly inhibits both pancreatic alpha-amylase and membrane-bound alpha-glucosidases—amylases whose inhibitory potency appears to follow the order: glucosidase > sucrase > maltase > isomaltase. Acarbose lowers postprandial blood glucose and insulin levels by blocking the metabolism and absorption of dietary carbohydrates. Unlike sulfonylureas, acarbose does not promote insulin secretion. Acarbose's hypoglycemic effect stems from its competitive and reversible inhibition of pancreatic α-amylase and membrane-bound intestinal α-glucosidase. Pancreatic α-amylase hydrolyzes complex starch into oligosaccharides in the small intestine, while membrane-bound intestinal α-glucosidase hydrolyzes oligosaccharides, trisaccharides, and disaccharides into glucose and other monosaccharides at the brush border of the small intestine. In diabetic patients, inhibition of these enzymes leads to delayed glucose absorption, thereby reducing postprandial hyperglycemia. Due to its different mechanism of action, acarbose's glycemic control-enhancing effect has an additive effect when used in combination with sulfonylureas, insulin, or metformin. Furthermore, acarbose can reduce the insulin-stimulating and weight-gaining effects of sulfonylureas. Acarbose has no inhibitory activity against lactase, therefore it is not expected to induce lactose intolerance. Acarbose is a drug that helps diabetic patients obtain metabolic benefits by inhibiting intestinal α-glucosidase through a potent competitive action, slowing carbohydrate absorption. Acarbose molecules bind to the carbohydrate-binding site of α-glucosidase with an affinity constant much higher than that of normal substrates. Since the interaction between the inhibitor and the enzyme is reversible, the conversion of oligosaccharides to monosaccharides is only delayed, not completely blocked. Acarbose has a tetrasaccharide structure and does not cross intestinal cells after ingestion. Therefore, its pharmacokinetic properties are well-suited for pharmacological action specifically targeting intestinal glucosidases. This study aimed to reveal the potential role of thyroid hormones in the hypoglycemic and antioxidant effects of acarbose. The study investigated the effects of acarbose on changes in serum thyroid hormone, insulin, and glucose concentrations in dexamethasone-induced type 2 diabetic mice. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) levels, and the activities of related endogenous antioxidant enzymes (such as superoxide dismutase (SOD) and catalase (CAT)) in commonly affected diabetic tissues—the kidneys and heart—were investigated. Although intramuscular dexamethasone (1.0 mg/kg, for 22 consecutive days) caused hyperglycemia, accompanied by elevated serum insulin and tissue LPO levels, it reduced thyroid hormone concentrations and the activities of SOD and CAT. When mice treated with dexamethasone-induced hyperglycemia by acarbose (10 mg/kg/day, orally, for 15 consecutive days), elevated thyroid hormone levels were reversed, and most abnormal indicators, including serum insulin and glucose levels, tissue lipid peroxide (LPO), superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) levels, were reversed. These results suggest that thyroid hormones are involved in the mechanism by which acarbose improves type 2 diabetes. Acarbose is a novel oral hypoglycemic agent approved for the treatment of non-insulin-dependent diabetes mellitus. It slows the digestion and absorption of complex carbohydrates by inhibiting α-glucosidase in the small intestine. Therefore, postprandial blood glucose elevation is smaller, and glycated hemoglobin decreases by an overall 0.5-1.0%. The potential advantages of acarbose include more effective control of postprandial hyperglycemia, a low risk of hypoglycemia, and the potential to delay the initiation of insulin therapy. Acarbose can enhance the hypoglycemic effects of sulfonylureas or insulin. It does not cause weight gain or hyperinsulinemia, both of which can occur with the use of sulfonylureas or insulin. Common gastrointestinal adverse reactions to acarbose may be reduced with continued treatment. Although rare, there have been reports of elevated serum transaminase levels. [1]

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Acarbose is an α-glucosidase inhibitor that specifically targets postprandial blood glucose fluctuations. The compound can reduce glycated hemoglobin (HbA1c) by 0.5–1% in patients with type 2 diabetes, regardless of whether the patient has received hypoglycemic agents. In patients with impaired glucose tolerance (IGT), it can reduce the incidence of newly diagnosed diabetes by 36.4%. In addition, acarbose is beneficial for overweight patients, can lower blood pressure and triglyceride levels, and downregulate biomarkers of low-grade inflammation. In the STOP-NIDDM trial, acarbose significantly slowed the progression of intimal media thickness, reduced the incidence of cardiovascular events, and decreased the incidence of newly diagnosed hypertension. In a meta-analysis of patients with type 2 diabetes (MERIA), acarbose administration was associated with a 35% reduction in the incidence of cardiovascular events. Acarbose is a very safe drug, but due to its mechanism of action, about 30% of patients may experience gastrointestinal discomfort, but most patients experience relief within 1–2 months. Acarbose has been approved in 25 countries for the treatment of impaired glucose tolerance (IGT). It can be used alone or in combination with other oral hypoglycemic agents and insulin. Acarbose is particularly effective for patients with impaired glucose tolerance (IGT), early-stage diabetes, and those with metabolic syndrome. [2]

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Acarbose is a synthetic α-glucosidase inhibitor used to treat non-insulin-dependent diabetes mellitus (NIDDM). It controls postprandial blood glucose levels by delaying glucose uptake. This study developed an immobilized α-glucosidase (AGH) detection system (βAla-iAGH) to better mimic the environment of membrane-bound enzymes in vivo. In the βAla-iAGH sucrase assay, the IC₅₀ ratio of acarbose and voglibose (19.4) was very close to the ED₅₀ ratio reported in Sprague-Dawley rats (14.6), suggesting that this immobilized system may be a better predictor of in vivo efficacy. [3]

C25H45NO22S

743.683309316635

743.215

1221158-13-9

Acarbose;56180-94-0

127255613

Typically exists as solid at room temperature

16

23

13

49

1030

18

C[C@@H]1[C@H]([C@@H]([C@H]([C@H](O1)O[C@@H]2[C@H](O[C@@H]([C@@H]([C@H]2O)O)O[C@H]([C@@H](CO)O)[C@@H]([C@H](C=O)O)O)CO)O)O)N[C@H]3C=C([C@H]([C@@H]([C@H]3O)O)O)CO.OS(=O)(=O)O

XHZAGRIRYDJUSP-PKCKZCPMSA-N

InChI=1S/C25H43NO18.H2O4S/c1-7-13(26-9-2-8(3-27)14(33)18(37)15(9)34)17(36)20(39)24(41-7)44-23-12(6-30)42-25(21(40)19(23)38)43-22(11(32)5-29)16(35)10(31)4-28;1-5(2,3)4/h2,4,7,9-27,29-40H,3,5-6H2,1H3;(H2,1,2,3,4)/t7-,9+,10+,11-,12-,13-,14-,15+,16-,17+,18+,19-,20-,21-,22-,23-,24-,25-;/m1./s1

(2R,3R,4R,5R)-4-(((2R,3R,4R,5S,6R)-5-(((2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-(((1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl)amino)tetrahydro-2H-pyran-2-yl)oxy)-3,4-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-2,3,5,6-tetrahydroxyhexanal sulfate

BAY-g-5421 sulfate; Acarbose sulfate; 1221158-13-9; (2R,3R,4R,5R)-4-[(2R,3R,4R,5S,6R)-5-[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino]oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,3,5,6-tetrahydroxyhexanal;sulfuric acid; BAY-g 5421; BAY g-5421 sulfate; Acarbose sulfate; Glucobay; Prandase; Precose

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)