Exploring the Inhibitory Mechanism of Res on Α-Amylase and Α-Glucosidase Via Enzymatic Inhibition Assay, Multi-Spectroscopic Analysis and Molecular Docking

对接(动物) 酶抑制 化学 淀粉酶 抑制性突触后电位 机制(生物学) 生物化学 生物 物理 医学 量子力学 护理部 神经科学
作者
Fuli Ma,Guoyan Ren,Mingyi Zhou,Ruoyao Pan,Bin Zhang,Jinling Fan
标识
DOI:10.2139/ssrn.4405914
摘要

Inhibition of α-amylase and α-glucosidase activities to delay the hydrolysis of starch to glucose has been considered as an effective strategy to control hyperglycemia. Resveratrol has been shown to have hypoglycemic effects, but its mechanism of inhibiting α-amylase and α-glucosidase activities remains unclear. The inhibitory effect of resveratrol on starch digestion, α-amylase and α-glucosidase activities and its mechanism were investigated by means of starch digestion experiment, enzyme reaction kinetics, multispectral and molecular docking techniques. Resveratrol can significantly reduce the digestibility of starch by inhibiting the activity of starch digestive enzymes or changing the microstructure of starch. Resveratrol inhibited α-amylase and α-glucosidase significantly, with IC50 values of 47.713 μg mL-1 and 26.825 μg mL-1, respectively. Resveratrol inhibited α-amylase in a competitive manner and α-glucosidase in a non-competitive manner. Uv-vis spectra showed that the microenvironment of α-amylase and α-glucosidase aromatic amino acid residues was changed by the addition of resveratrol. Multiple fluorescence spectra showed that resveratrol interacts with α-glucosidase and α-amylase through static quenching mechanism. The interaction of resveratrol and α-glucosidase and α-amylase is spontaneous with at least one binding site with α-glucosidase and α-amylase. Resveratrol interacts with α-glucosidase mainly through hydrogen bonding and van der Waals forces, but with α-amylase through hydrophobic interaction. The molecular docking results showed that resveratrol was bound to the active center of α-amylase and formed a competitive relationship with the substrate, while resveratrol was bound to the hydrophobic pocket of α-glucosidase. This study provides a new idea for the development of powerful drugs or functional foods containing resveratrol, and provides a new way to improve hyperglycemia.

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