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

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.

Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

“…During the last few years, flavonoids, including flavones, have attracted much interest because of their diverse bioactivities [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Recent studies have indicated the abilities of flavones in inhibiting many enzymes [ 25 , 26 , 27 , 28 , 29 ], especially AChE [ 30 ] and BACE-1 [ 31 , 32 ]. Studies on the bioactivity of flavone derivatives against AChE and BACE-1 are thus promising for the discovery of novel therapeutic agents for AD.…”

Molecular Elucidation of Pancreatic Elastase Inhibition by Baicalein

“…As per the results obtained from the in-vitro and in-silico findings, baicalein demonstrates the properties of a non-competitive inhibitor. Allosteric modulation has been previously reported for baicalein [31]. Non-competitive inhibition underlines the possibility of the inhibitor molecule binding to either the enzyme alone or the enzyme-substrate complex.…”

Robust Magnetized Graphene Oxide Platform for In Situ Peptide Synthesis and FRET-Based Protease Detection

“…Finally, we investigated whether the MGO platform can be used for the detection of β-secretase, which is considered to be an important Alzheimer’s disease marker [ 42 , 43 ]. The MGO FRET biosensors were incorporated with the β-secretase-specific peptide (EVNLDA) [ 44 ]. Fluorescence recovery was achieved by the cleavage of the peptide between Leu and Asp by β-secretase, resulting in the release of FITC-EVNL.…”