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

Abstract

BACKGROUNDDiabetes 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.RESULTSThe 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.CONCLUSIONOverall, 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.

Synergistic interaction of Cu(II) with caffeic acid and chlorogenic acid in α‐glucosidase inhibition

“…This suggested that the interactions between the complexes and ⊍-glucosidase were primarily nonfluorescent, meaning that the binding of phenolic acids and complexes to ⊍-glucosidase did not interact more strongly with tryptophan residues, tyrosine residues, and phenylalanine residues (the main sources of endogenous fluorescence of the protein). 41 This was further confirmed by the molecular docking results below. The degree of change in the secondary structure of ⊍-glucosidase was greatest in the presence of copper ions but in terms of the degree of inhibition of enzyme activity CHA-Cu was the most inhibitory.…”

“…The inhibitory ability of phenolic acids was enhanced after binding to copper ions, which contradicted the result of fluorescence quenching. This suggested that the interactions between the complexes and α ‐glucosidase were primarily nonfluorescent, meaning that the binding of phenolic acids and complexes to α ‐glucosidase did not interact more strongly with tryptophan residues, tyrosine residues, and phenylalanine residues (the main sources of endogenous fluorescence of the protein) 41 . This was further confirmed by the molecular docking results below.…”

“…This suggested that the change in secondary structure may not be the main reason for the decrease in α ‐glucosidase activity. The primary, super‐secondary or tertiary structure of proteins may be the key factor affecting α ‐glucosidase activity, and changes in the microenvironment may also have a greater impact on enzyme activity 41 . Protein stability refers to the ability of a protein to resist the effects of various factors and maintain its biological viability.…”

“…The primary, super-secondary or tertiary structure of proteins may be the key factor affecting ⊍-glucosidase activity, and changes in the microenvironment may also have a greater impact on enzyme activity. 41 Protein stability refers to the ability of a protein to resist the effects of various factors and maintain its biological viability. Here, protein stability can represent the ability of ⊍-glucosidase to maintain enzyme activity.…”

Morinda scabrida Craib: An unexplored species with antibacterial potential and inhibition of acetylcholine esterase and α-glucosidase

“…Medicinal plants are rich sources of biologically active compounds with inhibitory activity against α-glucosidase (Wangkiri et al, 2021). In particular, gallic acid (Oboh et al, 2016;Choudhary et al, 2020;Xue et al, 2020;Kokila et al, 2022), theaflavin-3-gallate (Li et al, 2021) and epigallocatechin gallate ( Li et al, 2007;Xu et al, 2019;Guan et al, 2023) exhibited anti α-glucosidase activity. Consequently, it is anticipated that M01-M05 would exhibit inhibitory activity against α-glucosidase.…”