Exploring the Inhibition of Quercetin on Acetylcholinesterase by Multispectroscopic and In Silico Approaches and Evaluation of Its Neuroprotective Effects on PC12 Cells

Abstract

This study investigated the inhibitory mechanism of quercetin in acetylcholinesterase (AChE) and its neuroprotective effects on β-amyloid25–35-induced oxidative stress injury in PC12 cells. Quercetin inhibited AChE in a reversible mixed manner with an IC50 of 4.59 ± 0.27 µM. The binding constant of quercetin with AChE at 25 °C was (5.52 ± 0.05) × 104 L mol−1. Hydrogen bonding and van der Waals forces were the main interactions in forming the stable quercetin–AChE complex. Computational docking revealed that quercetin was dominant at the peripheral aromatic site in AChE and induced enzymatic allosterism; meanwhile, it extended deep into the active center of AChE and destabilized the hydrogen bond network, which caused the constriction of the gorge entrance and prevented the substrate from entering the enzyme, thus resulting in the inhibition of AChE. Molecular dynamics (MD) simulation emphasized the stability of the quercetin–AChE complex and corroborated the previous findings. Interestingly, a combination of galantamine hydrobromide and quercetin exhibited the synergistic inhibition effect by binding to different active sites of AChE. In a β-amyloid25–35-induced oxidative stress injury model in PC12 cells, quercetin exerted neuroprotective effects by increasing the glutathione level and reducing the malondialdehyde content and reactive oxygen species levels. These findings may provide novel insights into the development and application of quercetin in the dietary treatment of Alzheimer’s disease.

Chemical characterization and biological abilities of Anthocleista djalonensis collected from two locations of Ivory Coast

“…Similarly, neuroprotection by a flavonoid quercetin has been reported in several in vitro studies (Khan et al, 2019). In a study by Liao et al (2022), quercetin showed significant AChE inhibitory activity and the double bond at positions C2 and C3 in quercetin structure played a key role in the inhibition of AChE. In another study by Kim et al (2011), gallic acid exhibited stronger AChE inhibitory effect when compared with catechin and epicatecthin.…”

The Effect of a Tribulus-Based Formulation in Alleviating Cholinergic System Impairment and Scopolamine-Induced Memory Loss in Zebrafish (Danio rerio): Insights from Molecular Docking and In Vitro/In Vivo Approaches

“…The majority of the inner surface is composed of aromatic amino acids (Phe295, Phe338, and Tyr337). The PAS at the gorge entrance is predominantly composed of five residues: Asp74, Tyr72, Tyr124, Tyr341, and Trp286 [ 37 ]. The docked scores of 15 compounds against AChE ranged from −11.22 to −24.68 kcal/mol, compared to −14.62 kcal/mol for donepezil (co-crystal ligand) ( Table 2 and Table S1 ).…”

Exploring the effect and mechanism of Aloin A against cancer cachexia-induced muscle atrophy via network pharmacology, molecular docking, molecular dynamics and experimental validation

“…To investigate the stability of Aloin A binding to selected proteins, we calculated the RMSD of the skeleton atoms in the simulated trajectory. RMSD has been commonly used to estimate the degree of protein deviation from the original structure, which explains the stability of the complex [ 29 ]. As shown in Figure 7A , the plot of the HSP90AA1-Aloin A complex showed a stable equilibrium approximately after 15 ns, then a stable RMSD could be seen approximately at ~0.20 nm.…”