Molecular insights into α-glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (-)-epigallocatechin-3-gallate

J Sci Food Agric. 2023 Dec;103(15):7381-7392. doi: 10.1002/jsfa.12818. Epub 2023 Jul 11.

Abstract

Background: Diabetes mellitus poses a substantial threat to public health due to rising morbidity and mortality. α-Glucosidase is one of the key enzymes affecting diabetes. Herein, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) were applied to clarify the role of the galloyl moiety of tea polyphenols in the inhibition of glycation and α-glucosidase activity. The structure-activity relationship of the galloyl moiety in EGCG on α-glucosidase was investigated in terms of inhibition kinetics, spectroscopy, atomic force microscopy and molecular docking. A bovine serum protein-fructose model was employed to determine the effect of the galloyl moiety on glycation.

Results: The results indicated that the introduction of a galloyl moiety enhanced the capacity of EGCG to inhibit glycation and α-glucosidase activity. The IC50 value of EGC is approximately 2400 times higher than that of EGCG. Furthermore, the galloyl moiety in EGCG altered the microenvironment and secondary structure of α-glucosidase, resulting in a high binding affinity of EGCG to α-glucosidase. The binding constant of EGCG to α-glucosidase at 298 K is approximately 28 times higher than that of EGC.

Conclusion: Overall, the galloyl moiety of EGCG plays a crucial role in inhibiting glycation and α-glucosidase activity, which helps to enhance the molecular understanding of the structure and function of the polyphenol galloyl moiety in the science of food and agriculture. © 2023 Society of Chemical Industry.

Keywords: fluorescence quenching; inhibition mechanism; molecular docking; polyphenol-protein interaction; structure-activity relationship.

MeSH terms

  • Catechin* / chemistry
  • Catechin* / pharmacology
  • Molecular Docking Simulation
  • Polyphenols / chemistry
  • Spectrum Analysis
  • Tea / chemistry
  • alpha-Glucosidases* / metabolism

Substances

  • epigallocatechin gallate
  • alpha-Glucosidases
  • Catechin
  • Polyphenols
  • Tea