Dietary Flavonoids and Acarbose Synergistically Inhibit α-Glucosidase and Lower Postprandial Blood Glucose

Abstract

The inhibition of porcine pancreatic α-amylase and mammalian α-glucosidase by 16 individual flavonoids was determined. The IC values for baicalein, (+)-catechin, quercetin, and luteolin were 74.1 ± 5.6, 175.1 ± 9.1, 281.2 ± 19.2, and 339.4 ± 16.3 μM, respectively, against α-glucosidase. The IC values for apigenin and baicalein were 146.8 ± 7.1 and 446.4 ± 23.9 μM, respectively, against α-amylase. The combination of baicalein, quercetin, or luteolin with acarbose showed synergistic inhibition, and the combination of (+)-catechin with acarbose showed antagonistic inhibition of α-glucosidase. The combination of baicalein or apigenin with acarbose showed additive inhibition of α-amylase at lower concentrations and antagonistic inhibition at a higher concentration. Kinetic studies of α-glucosidase activity revealed that baicalein alone, acarbose alone, and the combination showed noncompetitive, competitive, and mixed-type inhibition, respectively. Molecular modeling revealed that baicalein had higher affinity to the noncompetitive binding site of maltase, glucoamylase, and isomaltase subunits of α-glucosidase, with glide scores of -7.64, -6.98, and -6.88, respectively. (+)-Catechin had higher affinity to the active sites of maltase and glucoamylase and to the noncompetitive site of isomaltase. After sucrose loading, baicalein dose-dependently reduced the postprandial blood glucose (PBG) level in mice. The combination of 80 mg/kg baicalein and 1 mg/kg acarbose synergistically lowered the level of PBG, and the hypoglycemic effect was comparable to 8 mg/kg acarbose. The results indicated that baicalein could be used as a supplemental drug or dietary supplement in dietary therapy for diabetes mellitus.

Inhibitory Actions of Lagerstroemia speciosa (L.) Pers. Aqueous and Ethanolic Leaf Extracts against Carbohydrate-digesting Enzymes

“…On the other hand, the competitive inhibition against α-glucosidase of acarbose was demonstrated earlier. 26 Nonetheless, it should be noted that the levels of K m increment and V max reduction found in this study were only trivial in the presence of the LSA extract and acarbose, respectively. The inhibition constants (K i ) of both extracts against α-amylase were lower than that of acarbose.…”

Isolation and Characterization of Antihyperglycemic Compounds from Vigna angularis Extracts

“…A previous report identified C7G, E7G, and catechin in an ABE as antioxidants (Hori et al., ), and these compounds were shown to suppress antigen‐stimulated degranulation in leukemic cells (Itoh et al., ). Catechin has multiple biological functions, including the inhibition of α‐amylase and α‐glucosidase (Tadera et al., ), with the latter reported to occur via direct binding to the active site of α‐glucosidase (Zhang et al., ). Similarly to the previous reports, in this study, catechin showed inhibitory activity toward α‐amylase and α‐glucosidase (IC 50 values: α‐amylase, 0.30 mg/mL; α‐glucosidase, 0.033 mg/mL, data not shown).…”

Inhibitory effect of corosolic acid on α‐glucosidase: kinetics, interaction mechanism, and molecular simulation

“…21 The IC 30 , IC 50 , and IC 70 values of myricetin were 1.12, 1.68, and 1.76 × 10 −6 mol L −1 , respectively, suggesting a strong inhibition against -glucosidase. Meanwhile, the values of IC 30 , IC 50 , and IC 70 of CRA were 11.3, 13.5, and 19.5 × 10 −6 mol L −1 .…”

“…D X in the denominator is the dose that inhibits X% enzyme activity by single inhibitor. Based on the CI values, the interaction can be classified as synergism (CI < 0.9), addition (CI = 0.9–1.1), or antagonism (CI >1.1) …”

“…Based on the CI values, the interaction can be classified as synergism (CI < 0.9), addition (CI = 0.9-1.1), or antagonism (CI >1.1). 30 Measurements of fluorescence spectra Different amounts of CRA were successively titrated to a 3 mL -glucosidase (8.7 × 10 −7 mol L −1 ) solution. Their fluorescence spectra were then scanned by a spectrofluorimeter (Model F-7000, Hitachi, Japan) at the following temperatures (298, 304, and 310 K).…”