Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.
Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer's disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-D-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.
['Bhakta|Himanshu Kumar|HK|', 'Park|Chan Hum|CH|', 'Yokozawa|Takako|T|', 'Tanaka|Takashi|T|', 'Jung|Hyun Ah|HA|', 'Choi|Jae Sue|JS|']
D000110:Acetylcholinesterase D000544:Alzheimer Disease D053829:Amyloid Precursor Protein Secretases D016282:Aspartic Acid Endopeptidases D002091:Butyrylcholinesterase D002800:Cholinesterase Inhibitors D029768:Cornus D004305:Dose-Response Relationship, Drug D005638:Fruit D005960:Glucosides D006801:Humans D047348:Hydrolyzable Tannins D062105:Molecular Docking Simulation D010936:Plant Extracts D011714:Pyrans
Cornuside Gallotannin Cholinesterase BACE1 Peroxynitrite-mediated protein tyrosine nitration Alzheimer’s disease Molecular docking simulation