Mechanistic study on the inhibition of α‐amylase and α‐glucosidase using the extract of ultrasound‐treated coffee leaves

Our previous studies have shown that ultrasound-treated γ-aminobutyric acid (GABA)-rich coffee leaves have higher angiotensin-I-converting enzyme inhibitory activity than their untreated counterpart. However, whether they have antidiabetic activity remains unknown. In this study, we aimed to investigate the inhibitory activities of coffee leaf extracts (CLEs) prepared with ultrasound (CLE-U) or without ultrasound (CLE-NU) pretreatment on α-amylase and α-glucosidase. Subsequently, we evaluated the binding interaction between CLE-U and both enzymes using multi-spectroscopic and in silico analyses.Ultrasound pretreatment increased the inhibitory activities of CLE-U against α-amylase and α-glucosidase by 21.78% and 25.13%, respectively. CLE-U reversibly inhibits both enzymes, with competitive inhibition observed for α-amylase and non-competitive inhibition for α-glucosidase. The static quenching of CLE-U against both enzymes was primarily driven by hydrogen bond and van der Waals interactions. The α-helices of α-amylase and α-glucosidase were increased by 1.8% and 21.3%, respectively. Molecular docking results showed that the key differential compounds, including mangiferin, 5-caffeoylquinic acid, rutin, trigonelline, GABA, caffeine, glutamate, and others, present in coffee leaves interacted with specific amino acid residues located at the active site of α-amylase (ASP197, GLU233, and ASP300). The binding of α-glucosidase and these bioactive components involved amino acid residues, such as PHE1289, PRO1329, and GLU1397, located outside the active site.Ultrasound-treated coffee leaves are potential anti-diabetic substances, capable of preventing diabetes by inhibiting the activities of α-amylase and α-glucosidase, thus delaying starch digestion. Our study provides valuable information to elucidate the possible antidiabetic capacity of coffee leaves through the inhibition of α-amylase and α-glucosidase activities. © 2023 Society of Chemical Industry.