Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits

• DOI: 10.1007/s12272-017-0924-z
• Publication Date: 2017-06-06T10:57:44Z
• Authors: Himanshu Kumar Bh...; Chan Hum Park; Takako Yokozawa; Takashi Tanaka; Hyun Ah Jung; Jae Sue Choi
• Keywords: 0301 basic medicine; Dose-Response Relationship, Drug; Plant Extracts; Hydrolyzable Tannins; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Cornus; Glucosides; Alzheimer Disease; Butyrylcholinesterase; Fruit; Acetylcholinesterase; Aspartic Acid Endopeptidases; Humans; Cholinesterase Inhibitors; Amyloid Precursor Protein Secretases; Pyrans

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.