Hesperetin-Cu(II) complex as potential a-amylase and a-glucosidase inhibitor: Inhibition mechanism and molecular docking

Inhibition of a-amylase and a-glucosidase activity is an effective way for controlling postprandial blood glucoserelated diabetes. The study found that hesperetin-Cu(II) complex (Hsp-Cu(II)) exhibited a stronger inhibitory ability on a-amylase and a-glucosidase compared to hesperetin (Hsp), with smaller IC50 values of Hsp-Cu(II) (60.3 +/- 0.9 mu M for a-amylase; 1.25 +/- 0.03 mu M for alpha-glucosidase) than Hsp (115.6 +/- 1.1 mu M for alpha-amylase; 55.2 +/- 0.1 mu M for a-glucosidase). Interestingly, Hsp-Cu(II) and acarbose exerted a synergistic effect on inhibition of alpha-glucosidase. The binding affinities of Hsp-Cu(II) to a-amylase and alpha-glucosidase were strong with the Ka values (binding constant) in the magnitude order of 10(5), which was 9 times larger than Hsp. After interacting, Hsp-Cu(II) reduced alpha-helix contents of a-amylase and a-glucosidase, resulting in a looser conformation of these two enzymes. Molecular simulations manifested that Hsp-Cu(II) bound to the active center of enzymes driven by hydrogen bonds and interacted with the key catalytic amino acids (a-amylase: Gln63, Asp300 and His305; a-glucosidase: Tyr158, Asp215, Glu277 and Glu411), altering the conformation of enzymes, blocking the entrance of substrates, ultimately reducing the activities of a-glucosidase and a-amylase. This study has demonstrated that Hsp-Cu(II) may be a promising candidate of functional nutritional additive and medicine for the prevention of diabetes.

Automated summary

Inhibition of a-amylase and a-glucosidase activity is effective in controlling postprandial blood glucose in diabetes. The study showed that Hsp-Cu(II) exhibited stronger inhibitory ability on these enzymes compared to Hsp, with smaller IC50 values. Hsp-Cu(II) and acarbose also synergistically inhibited alpha-glucosidase. Molecular simulations revealed that Hsp-Cu(II) bound to the active center of the enzymes, altering their conformation and reducing their activities.