Insight into interaction mechanism between theaflavin-3-gallate and α-glucosidase using spectroscopy and molecular docking analysis

To elucidate the α-glucosidase (α-GC) inhibitory mechanism of theaflavin-3-gallate (TF-3-G), their interaction mechanism was investigated using spectroscopy and molecular docking analysis. The inhibition ratio of TF-3-G against α-GC was determined to be 92.3%. Steady fluorescence spectroscopy showed that TF-3-G effectively quenched the intrinsic fluorescence of α-GC through static quenching, forming a stable complex through hydrophobic interactions. Formation of the TF-3-G/α-GC complex was also confirmed by resonance light scattering spectroscopy. Synchronous fluorescence spectroscopy and circular dichroism spectroscopy indicated that the secondary structure of α-GC was changed by TF-3-G. Molecular docking was used to simulate TF-3-G/α-GC complex formation, showing that TF-3-G might be inserted into the hydrophobic region around the active site of ɑ-GC, and bind with the catalytic Asp215 and Asp352 residues. The ɑ-GC inhibitory mechanism of TF-3-G was mainly attributed to the change in ɑ-GC secondary structure caused by the complex formation. Practical applications α-Glucosidase (α-GC) can hydrolyze the glycosidic bonds of starch and oligosaccharides in food and release glucose. Therefore, the inhibition of α-GC activity has been used to treat postprandial hyperglycemia and type 2 diabetes mellitus. Theaflavin-3-gallate (TF-3-G), a flavonoid found in the fermentation products of black tea, exhibits strong inhibition of α-GC activity. However, the α-GC inhibitory mechanism of TF-3-G is unclear. This study aids understanding of this mechanism, and proposed a possibly basic theory for improving the medicinal value of TF-3-G in diabetes therapy.