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

Abstract

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 Cotinus coggygria Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC50 value of 4.099 × 10−4 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−1. 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 Cotinus coggygria Scop. is a promising therapeutic agent for the treatment of T2DM.

A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis

“…α-Glucosidase inhibitors (AGIs) are first-line drugs to treat diabetes mellitus (DM), and phenolics from plants are excellent sources of AGIs with high efficiency and low side effect ( 35 ). From Figures 3A,B , all samples had significantly α-glucosidase inhibitory abilities in a dose-dependent manner.…”

Analysis of Isoflavones in Pueraria by UHPLC-Q-Orbitrap HRMS and Study on α-Glucosidase Inhibitory Activity

“…Molecular docking analysis was performed to explore the structure-activity relationships of these compounds ( Figure 4 ) and the findings were consistent with the α-glucosidase inhibition test. The method of molecular docking provides new perspective for the study of active substances in food [ 35 , 36 ]. 3′-Methoxy puerarin was the most potent compound, with a docking energy of −7.9 kcal/mol (the same as the positive control acarbose).…”

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease

“…Fisetin is a natural dietary flavonoid that mainly exists in various fruits and vegetables, such as apples, grapes, cucumbers, and onions [ 163 ]. Through kinetic and molecular docking studies, it was found that fisetin had a potential inhibitory effect on α-glucosidase, which was verified by in vitro experiments [ 164 , 165 ]. Fisetin also has antioxidant, anti-inflammatory, and lipid metabolism-regulating activities [ 166 , 167 ], which can prevent the development of diabetes cardiomyopathy, diabetic neuropathy, and diabetes encephalopathy [ 168 , 169 , 170 ].…”