Inhibitory Effect of Fisetin on α-Glucosidase Activity: Kinetic and Molecular Docking Studies

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 17; p. 5306
• Main Authors: Shen, Beiyun, Shangguan, Xinchen, Yin, Zhongping, Wu, Shaofu, Zhang, Qingfeng, Peng, Wenwen, Li, Jingen, Zhang, Lu, Chen, Jiguang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31-08-2021; MDPI
• Subjects: alpha-Glucosidases - metabolism; Binding sites; Chemical compounds; Cotinus coggygria; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Enzymes; Evaluation; fisetin; Flavonoids; Flavonols - chemistry; Flavonols - pharmacology; Fluorescence; Glucose; Glucosidase; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Hyperglycemia; Insulin resistance; Metabolism; Molecular docking; Molecular Docking Simulation; Pharmacology; Proteins; Software; Spectrometry; α-Glucosidase; α-glucosidase inhibition; La Jolla California; United States > US; China; α-glucosidase inhibition; fisetin; molecular docking; diabetes
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26175306

The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from
Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC
value of 4.099 × 10
mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol
. Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from
Scop. is a promising therapeutic agent for the treatment of T2DM.