文章基本信息

标题：Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches
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作者：Jin Han ; Yeongseon Ji ; Kumju Youn 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2019
卷号：11
期号：11
页码：2694-2704
DOI：10.3390/nu11112694
出版社：MDPI Publishing
摘要：One of the major neurodegenerative features of Alzheimer’s disease (AD) is the presence of neurotoxic amyloid plaques composed of amyloid beta peptide (Aβ). β-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Aβ fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), the major efflux pump of the blood-brain barrier (BBB), plays a critical role in limiting therapeutic molecules. In pursuit of discovering a natural anti-AD candidate, the bioactivity, physicochemical, drug-likeness, and molecular docking properties of baicalein, a major compound from Scutellaria baicalensis, was investigated. Baicalein exhibited strong BACE1 and AChE inhibitory properties (IC50 23.71 ± 1.91 µM and 45.95 ± 3.44 µM, respectively) and reacted in non-competitive and competitive manners with substrates, respectively. in Silico docking analysis was in full agreement with the in vitro results, demonstrating that the compound exhibited powerful binding interaction with target enzymes. Particularly, three continuous hydroxyl groups on the A ring demonstrated strong H-bond binding properties. It is also noteworthy that baicalein complied with all requirements of Lipinski’s rule of five by its optimal physicochemical properties for both oral bioavailability and blood–brain barrier permeability. Overall, the present study strongly demonstrated the possibility of baicalein having in vivo pharmacological efficacy for specific targets in the prevention and/or treatment of AD.
关键词：Alzheimer’s disease; Aβ; baicalein; BACE1; docking analysis; Lipinski’s rules Alzheimer’s disease ; Aβ ; baicalein ; BACE1 ; docking analysis ; Lipinski’s rules