Discovery of Natural Inhibitors of Cholinesterases from Hydrangea : In Vitro and In Silico Approaches

• Published in: Nutrients 2021-01, Vol.13 (1), p.254
• Main Authors: Hwang, Jayeong, Youn, Kumju, Lim, Gyutae, Lee, Jinhyuk, Kim, Dong Hyun, Jun, Mira
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer Disease - enzymology; Alzheimer's disease; Alzheimer’s disease (AD); Amyloid beta-Peptides - metabolism; Binding Sites; Brain research; Butyrylcholinesterase - metabolism; Cholinesterase; Cholinesterase inhibitors; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Cognitive ability; Enzymes; Humans; Hydrangea; Hydrangea - chemistry; hydrangenol 8-O-glucoside pentaacetate; Hydrogen bonds; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Inhibitors; Isocoumarins; Kinetics; molecular docking; Molecular Docking Simulation; Plant Extracts - chemistry; Proteins; Senile plaques; Statistical analysis; Structure-Activity Relationship; thunberginol C; β-Amyloid
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13010254

Alzheimer's disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8- -glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS.