Alpha-glucosidase (IC50 = 11 nM)
The proliferation and migration of VSMC generated by TNF-α were reduced by acarbose (1, 2, and 3 μM) when dose and time were coupled. Acarbose (1, 2 and 3 μM) dose coupling decreased β-galactosidase and Ras expression while increasing p-AMPK expression in TNF-α-cleaved A7r5 [5].

The proliferation and migration of VSMC generated by TNF-α were reduced by acarbose (1, 2, and 3 μM) when dose and time were coupled. Acarbose (1, 2 and 3 μM) dose coupling decreased β-galactosidase and Ras expression while increasing p-AMPK expression in TNF-α-cleaved A7r5 [5].

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In TNF-α (20 ng/ml) pre-treated A7r5 vascular smooth muscle cells (VSMCs), Acarbose (1, 2, and 3 μM) co-treatment for 24 and 48 hours dose- and time-dependently inhibited cell proliferation, as measured by the MTT assay.[1]
In TNF-α (20 ng/ml) pre-treated A7r5 cells, Acarbose (1, 2, and 3 μM) co-treatment for 24 and 48 hours dose-dependently inhibited cell migration in a wound healing assay.[1]
Western blot analysis showed that in TNF-α (20 ng/ml) pre-treated A7r5 cells, Acarbose (1, 2, and 3 μM) co-treatment for 24 hours dose-dependently decreased the expression of aging-related proteins β-galactosidase and Ras, and increased the expression of phosphorylated AMP-activated protein kinase (p-AMPK).[1]
Western blot analysis showed that Acarbose (3 μM) co-treatment for 24 hours restored p-AMPK expression in A7r5 cells pre-treated with TNF-α and the AMPK inhibitor Compound C (5 μM). Similarly, Acarbose (3 μM) restored iNOS expression in cells pre-treated with TNF-α and the iNOS inhibitor L-NAME (0.5 mM).[1]

Rather than lowering body weight, acarbose (300 mg/60 kg body weight) lowers fasting blood pressure and modifies diabetic readings by supplementation. Acarbose dramatically reduces TNF-α and DM serum IL6[4]. Neointimal p-AMPK staining was dramatically raised while neointimal IL-6, TNF-α, and iNOS staining was significantly and dose-dependently lowered by acarbose (2.5 and 5.0 mg/kg). In HCD-fed rabbits, neointimal Ras and β-galactosidase expression were dramatically and dose-dependently decreased by acarbose (2.5 and 5.0 mg/kg) without causing weight loss [5].

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In New Zealand white rabbits fed a high-cholesterol diet (HCD) for 25 weeks, oral administration of Acarbose (2.5 and 5.0 mg kg⁻¹ per day) significantly and dose-dependently reduced the percentage of aortic arch area stained with atherosclerotic plaques (Oil Red O staining) compared to the HCD-only group.[1]
Histopathological (H&E) staining of aortic arches from HCD-fed rabbits showed that treatment with Acarbose (2.5 and 5.0 mg kg⁻¹ per day) significantly and dose-dependently reduced intimal hyperplasia.[1]
Immunohistochemical analysis of aortic arches from HCD-fed rabbits showed that treatment with Acarbose (2.5 and 5.0 mg kg⁻¹ per day) significantly and dose-dependently decreased neointimal expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA).[1]
Immunohistochemical analysis of aortic arches from HCD-fed rabbits showed that treatment with Acarbose (2.5 and 5.0 mg kg⁻¹ per day) significantly and dose-dependently decreased neointimal expression of inflammatory markers IL-6 and TNF-α, and increased the expression of inducible nitric oxide synthase (iNOS) and phosphorylated AMP-activated protein kinase (p-AMPK).[1]
Immunohistochemical analysis of aortic arches from HCD-fed rabbits showed that treatment with Acarbose (2.5 and 5.0 mg kg⁻¹ per day) significantly and dose-dependently decreased neointimal expression of aging-associated proteins Ras and β-galactosidase.[1]
Treatment with Acarbose (2.5 and 5.0 mg kg⁻¹ per day) did not significantly affect the body weight or serum levels of triglyceride, total cholesterol, LDL-C, and glucose in HCD-fed rabbits.[1]

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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AGH was partially purified from rat intestinal acetone powder. The powder was homogenized with papain in PCC buffer, incubated, centrifuged, and subjected to ammonium sulfate fractionation (40–60% saturation). The precipitate was dissolved, dialyzed, ultrafiltered, and lyophilized.[3]
For the immobilized AGH (iAGH) assay, cyanogen bromide-activated Sepharose 4B support was used. The gel was activated with HCl, rinsed, and coupled with the prepared AGH in borate buffer. After incubation, the support was blocked with reagents like β-alanine, 2-aminoethanol, n-propylamine, or ethylenediamine to introduce different functional groups, then rinsed thoroughly.[3]
iAGH activity was assayed by placing the iAGH support in a mini-column, adding model intestinal fluid containing maltose or sucrose, and incubating with rotation. The reaction was stopped by filtration, and the liberated glucose in the filtrate was measured using a glucose assay kit. Maltase and sucrase activities were defined as the amount of enzyme hydrolyzing 1 μmol of substrate per minute.[3]
For the iAGH inhibitory assay, the iAGH support was incubated with inhibitor solution and substrate solution. After incubation, the liberated glucose was measured. Inhibitory activity was calculated from the difference in glucose produced with and without the inhibitor. IC50 was defined as the inhibitor concentration causing 50% inhibition.[3]
The free AGH (fAGH) inhibitory assay used the same quantity of enzyme as the iAGH system. The same substrate concentrations and incubation times were used, and the liberated glucose was measured.[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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For the cell viability (MTT) assay, A7r5 cells were seeded in 24-well plates at a density of 2 × 10⁴ cells/well and incubated for 48 hours. Cells were pre-treated with TNF-α (20 ng/ml) and then co-treated with varying concentrations of Acarbose (0, 1, 2, or 3 μM) for 24 or 48 hours. Subsequently, MTT reagent (0.5 mg/ml) was added to each well and incubated for 4 hours at 37°C. The formazan product was solubilized with isopropanol, and absorbance was measured spectrophotometrically at 563 nm.[1]
For the wound healing (migration) assay, A7r5 cells were seeded in 6-well plates at a density of 1 × 10⁶ cells/ml and incubated for 48 hours to form a confluent monolayer. A straight scratch was made in each well using a sterile pipette tip. After washing with PBS to remove non-adherent cells, the remaining cells were treated with TNF-α (20 ng/ml) and co-treated with Acarbose (0, 1, 2, or 3 μM). Images of the wound area were taken at 0, 24, and 48 hours under a microscope. Migrated cells within the denuded zone were counted per well and averaged.[1]
For Western blot analysis, A7r5 cells were pre-treated with TNF-α (20 ng/ml) for 24 hours, followed by co-treatment with Acarbose (0, 1, 2, or 3 μM) for an additional 24 hours. Cells were then lysed. Protein lysates (50 μg per sample) were separated by SDS-PAGE on 8–12% gels and transferred to nitrocellulose membranes. Membranes were blocked with TBST containing nonfat milk, incubated with primary antibodies (specific for iNOS, Ras, p-AMPK, AMPK, β-galactosidase, etc.), followed by horseradish peroxidase-conjugated secondary antibodies. Protein bands were visualized using enhanced chemiluminescence and analyzed by densitometry.[1]
To investigate the role of AMPK and iNOS, A7r5 cells were pre-treated with TNF-α (20 ng/ml) for 24 hours, then incubated with the AMPK inhibitor Compound C (5 μM) or the iNOS inhibitor L-NAME (0.5 mM) for 30 minutes, followed by co-treatment with Acarbose (3 μM) for 24 hours. Cell lysates were then prepared for Western blot analysis as described above.[1]

Animal Models, Grouping, and Treatment [4]
Male 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.

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Animals and diets [5]
Twenty-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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Twenty-four male New Zealand White rabbits were randomly divided into four groups (n=6 per group). Group I received a standard chow diet. Groups II, III, and IV received a high-cholesterol diet (HCD; containing 95.7% standard chow + 3% lard oil + 0.5% cholesterol) for 25 weeks. Concurrently, Group III received Acarbose at a dose of 2.5 mg kg⁻¹ body weight per day, and Group IV received Acarbose at a dose of 5.0 mg kg⁻¹ body weight per day, mixed with their diet. The duration of treatment was 25 weeks. At the end of the study, rabbits were sacrificed under deep anesthesia. Blood was collected for serum analysis. The aortic arch and thoracic aorta were dissected, fixed, and processed for histological and immunohistochemical evaluation.[1]

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. Therapeutic doses of acarbose have a minor, but clinically insignificant, effect on the pharmacokinetics of rosiglitazone.

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In the cell viability (MTT) assay, acarbose at concentrations up to 3 μM did not show cytotoxicity in A7r5 cells. The test concentrations were up to 5 μM, with 3 μM being the highest non-toxic concentration used in the functional assay. [1]

[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.

Therapeutic Uses

Enzyme Inhibitor; Hypoglycemic Agent
Acarbose tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. /US Product Label Includes/
Therapeutic Category: Antidiabetic Agent
Drug Warnings

Acarbose is contraindicated in patients with known hypersensitivity to acarbose, diabetic ketoacidosis, or cirrhosis. It is also contraindicated in patients with inflammatory bowel disease, ulcerative colitis, partial intestinal obstruction, or those prone to intestinal obstruction. Furthermore, acarbose is contraindicated in patients with chronic intestinal disease accompanied by significant digestive or malabsorption, or in patients whose condition may be exacerbated by increased intestinal gas production.
Due to its mechanism of action, acarbose alone does not cause hypoglycemia in fasting or postprandial states. Sulfonylureas or insulin may cause hypoglycemia. The risk of hypoglycemia may increase when acarbose is used in combination with sulfonylureas or insulin, as this further lowers blood glucose levels. Hypoglycemia is generally not observed in patients using metformin alone, and no increase in the incidence of hypoglycemia was observed when acarbose was added to metformin treatment. For mild to moderate hypoglycemia, oral glucose (dextrose) should be used instead of sucrose (cane sugar) because acarbose does not inhibit glucose absorption. The hydrolysis of sucrose into glucose and fructose is inhibited by acarbose, making it unsuitable for rapid correction of hypoglycemia. Severe hypoglycemia may require intravenous glucose infusion or glucagon injection. Gastrointestinal symptoms are the most common adverse reaction to acarbose. …In a one-year safety study, patients kept a gastrointestinal symptom diary, and the results showed that abdominal pain and diarrhea tended to return to pre-treatment levels over time, while the frequency and intensity of bloating gradually decreased. Worsening gastrointestinal symptoms in patients receiving acarbose treatment are a manifestation of acarbose's mechanism of action and are related to undigested carbohydrates in the lower digestive tract. Gastrointestinal side effects may be exacerbated if a prescribed diet is not followed. If a patient experiences severe discomfort despite strictly adhering to a diabetic diet prescription, they must consult a doctor and consider a temporary or permanent dose reduction. In a long-term study conducted in the United States (up to 12 months, including acarbose doses up to 300 mg three times daily), the proportions of patients in the acarbose treatment group experiencing serum transaminase (AST and/or ALT) elevations above the upper limit of normal (ULN), exceeding 1.8 times the ULN, and exceeding 3 times the ULN during treatment were 14%, 6%, and 3%, respectively, compared to 7%, 2%, and 1% in the placebo group. Although these treatment differences were statistically significant, these elevations were asymptomatic, reversible, more common in women, and generally not accompanied by evidence of other liver dysfunction. Furthermore, these serum transaminase elevations appeared to be dose-related. In US studies, patients using acarbose at doses up to 100 mg three times daily (the maximum approved dose) experienced similar levels of AST and/or ALT elevations during treatment of any severity between the acarbose treatment group and the placebo group (p ≥ 0.496). For more complete (16) drug warnings for acarbose, please visit the HSDB records page.
Pharmacodynamics
Acarbose is a complex oligosaccharide that reduces carbohydrate absorption and subsequent postprandial insulin levels by competitively inhibiting the ability of brush border α-glucosidase to break down ingested carbohydrates into absorbable monosaccharides. Acarbose needs to be taken with carbohydrates to exert its therapeutic effect and should therefore be taken with the first bite of food at each meal, three times daily. Given its mechanism of action, the risk of hypoglycemia from acarbose alone is small; however, this risk is more pronounced when acarbose is used in combination with other hypoglycemic agents (such as sulfonylureas, insulin). Patients taking acarbose in combination with other hypoglycemic agents should be aware of the symptoms and risks of hypoglycemia and how to manage hypoglycemic episodes. Post-marketing reports indicate rare cases of pneumatosis cystoides intestinalis following treatment with α-glucosidase inhibitors—patients with significant diarrhea/constipation, mucus discharge, and/or rectal bleeding should be examined and treatment should be discontinued if pneumatosis cystoides is suspected. Acarbose is a clinical drug that controls postprandial hyperglycemia by inhibiting α-glucosidase activity in the small intestine. [1] This study suggests that, in addition to its hypoglycemic effect, acarbose may also exert a pleiotropic anti-atherosclerotic effect in rabbits by reducing vascular smooth muscle cell proliferation/migration, inflammation, and cellular senescence, which may be related to the upregulation of the AMPK signaling pathway. [1]

C25H43NO18

645.6048

645.247

C, 46.51; H, 6.71; N, 2.17; O, 44.61

56180-94-0

Acarbose sulfate;1221158-13-9

444254

White to light yellow solid powder

1.7±0.1 g/cm3

971.6±65.0 °C at 760 mmHg

165-170ºC

541.4±34.3 °C

0.0±0.6 mmHg at 25°C

1.689

-4.16

14

19

9

44

962

19

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]3[C@H](O[C@H]([C@@H]([C@H]3O)O)O)CO)CO)O)O)N[C@H]4C=C([C@H]([C@@H]([C@H]4O)O)O)CO

CEMXHAPUFJOOSV-XGWNLRGSSA-N

InChI=1S/C25H43NO18/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/h2,4,7,9-27,29-40H,3,5-6H2,1H3/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

BAY-g-5421; BAY-g 5421; acarbose; Precose; CAS-56180-94-0; BAY g-5421; Acarbose; 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)

H2O : ~100 mg/mL (~154.89 mM)

Solubility in Formulation 1: 100 mg/mL (154.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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