ABSTRACT
Acetylcholinesterase (AChE) inhibitors are mainly used in the treatment of Alzheimer's disease (AD). The inhibitory effect of icariin on the activity of AChE was investigated by inhibition kinetics. The binding interaction and binding sites between icariin and AChE were also studied by using fluorimetry and molecular docking, respectively. The results showed that icariin could potently inhibit the activity of AChE, the IC50 value was determined to be 3.50 x 10(-8) mol x L(-1), and the determined IC50 value to tacrine was 0.75 x 10(-8) mol x L(-1). Kinetic analyses showed that icariin is a reversible and mixed type AChE inhibitor. The inhibition constants K1 and K(IS) were determined to be 2.67 x 10(-8) and 4.43 x 10(-8) mol x L(-1), respectively. Icariin binds selectively to the AChE peripheral anionic site via hydrogen bonds and Van der Waals forces.
Subject(s)
Acetylcholinesterase , Metabolism , Binding Sites , Cholinesterase Inhibitors , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Epimedium , Chemistry , Flavonoids , Pharmacology , Hydrogen Bonding , Inhibitory Concentration 50 , Kinetics , Molecular Docking Simulation , Plants, Medicinal , ChemistryABSTRACT
The interaction between genistein and beta-glucosidase was studied using fluorescence quenching method and synchronous fluorimetry. The binding reaction was simultaneously studied by the AutoDock 4.2 molecular docking model. Data from fluorescence spectroscopy indicated that these interactions resulted in the endogenous fluorescence quenching of beta-glucosidase, which belongs to a static quenching mechanism. The calculated binding constants were 3.69 x 10(4), 3.06 x 10(4) and 2.36 x 10(4) L x mol(-1) at 17, 27 and 37 degrees C, respectively. The evidences from synchronous fluorescence showed the effect of genistein on the microenvironment around beta-glucosidase in aqueous solution. The inhibition test showed that the activity of beta-glucosidase could be inhibited by genistein. The determined bimolecular rate constant (k(i)) was 1.2 x 10(3) (mol x L(-1)(-1) x min(-1). Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that genistein could bind strongly to beta-glucosidase. The results revealed that genistein tended to bind with beta-glucosidase mainly by hydrogen bond and hydrophobic interaction as well as electrostatic forces.
