Inhibitory Effect of Genistein on <i>α</i>-Glucosidase and Its Molecular Mechanism

JIA Jianhui; DOU Boxin; GAO Man; ZHANG Chujia; LIU Ying; ZHANG Na

doi:10.13386/j.issn1002-0306.2024030182

Volume 46 Issue 5

Feb. 2025

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Science and Technology of Food Industry > 2025 > 46(5): 63-71. > DOI: 10.13386/j.issn1002-0306.2024030182

JIA Jianhui, DOU Boxin, GAO Man, et al. Inhibitory Effect of Genistein on α-Glucosidase and Its Molecular Mechanism[J]. Science and Technology of Food Industry, 2025, 46(5): 63−71. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024030182.

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Inhibitory Effect of Genistein on α-Glucosidase and Its Molecular Mechanism

College of Food Engineering, Harbin University of Commerce, Harbin 150028, China

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Received Date: March 13, 2024
Available Online: January 03, 2025

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Abstract

Abstract

To investigate the inhibitory effects of genistein on α-glucosidase activity, the effects of genistein on starch digestion characteristics were determined by in vitro digestion assays. The type and molecular mechanism of inhibition were examined based on enzyme kinetics, fluorescence spectroscopy, and molecular docking analyses. The results indicated that treatment with genistein significantly reduced the content of rapidly digestible starch (P<0.05) and promoted notable increases in the content of slowly digestible starch and resistant starch (P<0.05). Genistein inhibited α-glucosidase dose dependently, with an IC₅₀ value of 1.10±0.06 mg/mL, and the inhibition type was identified to be predominantly competitive within a mixed reversible inhibition. Genistein quenching the intrinsic fluorescence of α-glucosidase with a mixed pattern by binding to the ground state fluorescent groups and colliding with the excited state fluorescent groups. The binding free energy from molecular docking was less than -12 kJ/mol, indicating that the binding of genistein to α-glucosidase could occur spontaneously. Moreover, genistein targeted the hydrophobic pocket of α-glucosidase, forming hydrophobic interactions with residues Glu-429, Lys-432, and Ile-419, and hydrogen bonds with Gly-161, Asn-235, Asn-317, Glu-422, and His-423. These interactions contributed to stabilizing the binding of genistein to α-glucosidase, thereby reducing its catalytic activity. The findings provide theoretical support for the application of genistein in functional foods for blood glucose stabilization.
- genistein,
- starch digestion,
- α-glucosidase,
- inhibition,
- fluorescence spectroscopy,
- molecular docking

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