文章基本信息

标题：Inhibitory Mechanism of Baicalein on Acetylcholinesterase: Inhibitory Interaction, Conformational Change, and Computational Simulation
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作者：Yijing Liao ; Xing Hu ; Junhui Pan 等
期刊名称：Foods
电子版ISSN：2304-8158
出版年度：2022
卷号：11
期号：2
DOI：10.3390/foods11020168
语种：English
出版社：MDPI Publishing
摘要：Alzheimer’s disease (AD) is the most prevalent chronic neurodegenerative disease in elderly individuals, causing dementia. Acetylcholinesterase (AChE) is regarded as one of the most popular drug targets for AD. Herbal secondary metabolites are frequently cited as a major source of AChE inhibitors. In the current study, baicalein, a typical bioactive flavonoid, was found to inhibit AChE competitively, with an associated IC 50 value of 6.42 ± 0.07 µM, through a monophasic kinetic process. The AChE fluorescence quenching by baicalein was a static process. The binding constant between baicalein and AChE was an order of magnitude of 10 4 L mol −1, and hydrogen bonding and hydrophobic interaction were the major forces for forming the baicalein−AChE complex. Circular dichroism analysis revealed that baicalein caused the AChE structure to shrink and increased its surface hydrophobicity by increasing the α-helix and β-turn contents and decreasing the β-sheet and random coil structure content. Molecular docking revealed that baicalein predominated at the active site of AChE, likely tightening the gorge entrance and preventing the substrate from entering and binding with the enzyme, resulting in AChE inhibition. The preceding findings were confirmed by molecular dynamics simulation. The current study provides an insight into the molecular-level mechanism of baicalein interaction with AChE, which may offer new ideas for the research and development of anti-AD functional foods and drugs.
关键词：enbaicaleinacetylcholinesteraseinhibitory mechanismconformational changemolecular dockingmolecular dynamics simulation