Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant binding toward α-amylase with a binding constant (Ka) of the order of 104 M-1. The evaluation of thermodynamic parameters (∆H and ∆S) suggested that van der Waals force and hydrogen bonding drive seemingly specific hesperidin-α-amylase complex formation. Glycation and oxidation studies were performed using human serum albumin (HSA) as ideal protein. Hesperidin inhibited fructosamine content ≈40% at 50 µM and inhibited advanced glycation end products (AGEs) formation by 71.2% at the same concentration. Moreover, significant recovery was evident in free -SH groups and carbonyl content of HSA. Additionally, molecular docking also entrenched in vitro observations and provided an insight into the important residues (Trp58, Gln63, His101, Glu233, Asp300, and His305) at the heart of hesperidin-α-amylase interaction. This study delineates mechanistic insight of hesperidin-α-amylase interaction and provides a platform for use of hesperidin to treat AGEs directed diseases.
Keywords: Amylase; Docking; Hesperidin; Non-enzymatic glycation; Protein oxidation.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.