生物活性

Acarbose, also known as BAY g 5421, is an α-glucosidase inhibitor that prevents absorption of sucrose and maltose. The compound has been found to delay digestion of complex disaccharides and carbohydrates. Further studies suggest that this compound can stimulate phosphorylase kinase (PhK) by binding to the glucoamylase-like domain new the amino termini and causing an alteration in the structure. Inhibitor of intestinal α-glucosidase (IC50 = 11 nM). Antidiabetic; inhibits the hydrolysis of complex carbohydrates. Acarbose, an α-glucosidase inhibitor (AGI), is a commonly used oral glucose-lowering drug for the treatment of type 2 diabetes mellitus (T2DM).

Inhibitionof sucrose and maltose absorption rate from in situ perfused rat jejunal loopsby acarbose[1]

IC50value of acarbose was evaluated as 5.3 mg/mL (9.11 ±0.25mM) against α-glucosidase.[2]

IC50values of acarbose for porcine pancreatic α-amylase and rat small intestinalα-glucosidase activities[3]

体外研究

体内研究

激酶实验

Assessment of α-glucosidase inhibitory activity in vitro[2]

Inhibition assay of α-glucosidasewas performed according to the chromogenic method described. Yeast α-glucosidase(0.7 U/mL) dissolved in 100 mM phosphate buffer (pH 7.0) containing 2 g/Lbovine serum albumin and 0.2 g/L NaN₃ and5 mM p-nitrophenyl-α-D-glucopyranosidein the same buffer (pH 7.0) were used as an enzyme and a substrate solution,respectively. Then, 50 μL of enzyme solution and 10 μL of tested materialsdissolved in dimethylsulfoxide were mixed in a microplate well. The absorbanceof 405 nm at zero time was measured with a microplate reader. After incubationfor 5 min, 50 μL of substrate solution was added and incubated for anadditional 5 min at room temperature. The increase in absorbance from zero timewas measured. Each experiment was conducted in triplate. The IC50 values ofcompounds were calculated by the nonlinear regression analysis and expressed asthe mean ±SD of three distinctexperiments.

α-Glucosidase activity (sucrase: EC3.2.1.48, maltase: EC3.2.1.20) wasdetermined with minor modifications. Briefly, 500mg of rat intestinal acetone powderwas carefully homogenized with 10mL of 0.1M maleate buffer (pH6.9) in an OmniμH homogenizer, and then centrifuged at 5600g for 15min at 4 ^oC.The supernatant was used as α-glucosidase solution. Fifty microliters ofα-glucosidase solutionand100μL of sample (acarbose) dissolved in the buffer werepreincubated for 5min at 37^oC. Then, 50μL of 20mM sucrose or 2mM maltoseas substrate dissolved in the buffer was added to the reaction mixture to make atotal volume of 200μL, and the mixture was incubated for 30min at 37^oC.After the incubation, the reaction was terminated by heating with boiling waterfor 5min, and the reaction mixture was centrifuged at 10,000g for 5min. The amounof liberated glucose in the supernatant was determined by themutarotase–glucose oxidase method using Glucose CII-Test Wako according to the manufacturer'sinstructions. 

细胞实验

动物实验

Animals[4]

Male C57BL/KsJ mice and BKS.Cg-m +/+ Lepr^db/Jdb/db mice (db/db) with a C57BL/KsJ background were maintained in microisolatorcages on a 12 h light/dark cycle with controlled temperature (23 ± 2^oC) and humidity (about 70%) and received a standard laboratorypellet diet and water ad libitum.

ExperimentalProtocols

C57BL/6J mice were used as controls. Blood glucosewas monitored at the indicated time using a blood glucose monitoring systemwith whole blood obtained from the tail veins of the mice. On day 22, the micewith blood glucose levels greater than 250mg/dL were defined as db/db diabeticmice and subsequently treated with acarbose (50mg/kg/d, i.g.) treatment or vehicle(0.5% CMC-Na) for consecutive 14 days. The control mice received vehicle.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Krause HP KU, Puls W. Inhibition of disaccharide digestion in rat intestine by the alpha-glucosidase inhibitor acarbose (BAY g 5421). Digestion. . 1982;23(4):232-238.
[2] Choi CW, Choi YH, Cha MR, et al. Yeast alpha-glucosidase inhibition by isoflavones from plants of Leguminosae as an in vitro alternative to acarbose. J Agric Food Chem. 2010;58(18):9988-9993.
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体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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