High-throughput screening and investigation of the inhibitory mechanism of α-glucosidase inhibitors in teas using an affinity selection-mass spectrometry method

An affinity selection-mass spectrometry method was applied for high-throughput screening of a-glucosidase (AGH) inhibitors from teas. Fourteen out of nineteen screened AGH inhibitor candidates were clustered as galloylated polyphenols (GPs). AGH-GPs interaction studies, including enzyme kinetics, fluorescence spec-troscopy, circular dichroism, and molecular docking, jointly suggested that GPs noncompetitively inhibit AGH activity by interacting with amino acid residues near the active site of AGH and inducing changes in AGH secondary structure. Representative GPs and white tea extract (WTE) showed comparable AGH inhibition effects in Caco2 cells and postprandial hypoglycemic efficacy in diabetic mice as acarbose. The area under the curve of oral sucrose tolerance test was lower by 8.16%, 6.17%, and 7.37% than control group in 15 mg/kg EGCG, 15 mg/ kg strictinin, and 150 mg/kg WTE group, respectively. Our study presents a high-efficiency approach to discover novel AGH inhibitors and elucidates a potential mechanism by which tea decreases diabetes risks.

Automated summary

An affinity selection-mass spectrometry method was used to screen for α-glucosidase (AGH) inhibitors from teas, resulting in the identification of 14 galloylated polyphenols (GPs) out of 19 inhibitor candidates. Various studies suggested that GPs noncompetitively inhibit AGH activity by interacting with amino acid residues near the active site of AGH and inducing changes in AGH secondary structure. In cellular and animal experiments, representative GPs and white tea extract (WTE) showed comparable AGH inhibition effects and hypoglycemic efficacy as acarbose. These findings provide a high-efficiency approach to discover novel AGH inhibitors and explain the potential mechanism by which tea reduces diabetes risks.