Inhibitory Mechanism of Apigenin on α‑Glucosidase and Synergy Analysis of Flavonoids

• Published in: Journal of agricultural and food chemistry Vol. 64; no. 37; pp. 6939 - 6949
• Main Authors: Zeng, Li, Zhang, Guowen, Lin, Suyun, Gong, Deming
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.09.2016
• Subjects: active sites; alpha-glucosidase; alpha-Glucosidases - chemistry; apigenin; Apigenin - chemistry; circular dichroism spectroscopy; Drug Interactions; Flavonoids - chemistry; fluorescence; Glycoside Hydrolase Inhibitors - chemistry; Hydrogen Bonding; hydrophobic bonding; hyperglycemia; inhibitory concentration 50; Kinetics; Molecular Docking Simulation; myricetin; synergism; apigenin; α-glucosidase; inhibition mechanism; isobologram; synergy
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.6b02314

Inhibition of α-glucosidase activity may suppress postprandial hyperglycemia. The inhibition kinetic analysis showed that apigenin reversibly inhibited α-glucosidase activity with an IC50 value of (10.5 ± 0.05) × 10–6 mol L–1, and the inhibition was in a noncompetitive manner through a monophasic kinetic process. The fluorescence quenching and conformational changes determined by fluorescence and circular dichroism were due to the formation of an α-glucosidase–apigenin complex, and the binding was mainly driven by hydrophobic interactions and hydrogen bonding. The molecular simulation showed that apigenin bound to a site close to the active site of α-glucosidase, which may induce the channel closure to prevent the access of substrate, eventually leading to the inhibition of α-glucosidase. Isobolographic analysis of the interaction between myricetin and apigenin or morin showed that both of them exhibited synergistic effects at low concentrations and tended to exhibit additive or antagonistic interaction at high concentrations.