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Nutrients. 2019 Nov 7;11(11). pii: E2694. doi: 10.3390/nu11112694.

Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches.

Han J1,2, Ji Y1,2, Youn K1, Lim G3,4, Lee J3,4, Kim DH5,6, Jun M1,2,6.

Author information

1
Department of Food Science and Nutrition, College of Health Sciences, Dong-A University, Busan 49315, Korea.
2
Center for Silver-Targeted Biomaterials, Brain Busan 21 Plus Program, Graduate School, Dong-A University, Busan 49315, Korea.
3
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
4
Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Sciences and Technology, Daejeon 34113, Korea.
5
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Korea.
6
Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Korea.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Aβ; BACE1; Lipinski’s rules; baicalein; docking analysis

PMID:
31703329
DOI:
10.3390/nu11112694
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