Kashyap_2020_Neurosci.Insights_15_2633105520937693

Alzheimer's disease (AD) is characterized by depositions of amyloid beta (Abeta) peptides aggregates resulting in plaques formation in the central nervous system (CNS). This study evaluates the disease-modifying potential of scopoletin against multiple factors associated with AD such as cholinesterase enzymes, Abeta peptides, and neuroprotective properties against Abeta- and H(2)O(2)-induced cytotoxicity under in vitro conditions. Scopoletin was identified and quantified using UPLC-QTOF (ultra-high performance liquid chromatography-quadrupole time-of-flight) and high-performance liquid chromatography (HPLC), respectively. The antiamyloidogenic potential was evaluated by thioflavin T and congo red binding assay. Inhibition of key enzymes, that is, acetylcholinesterase and butyrylcholinesterase, was investigated by Ellman's assay. UPLC-QTOF analysis showed that most abundant phytoconstituent present in Argyreia speciosa hydroalcoholic root extract was scopoletin followed by festuclavine and ergometrine. Scopoletin was further quantified using novel reverse phase (RP)-HPLC method developed in this study. The neuroprotective potential of scopoletin was found to be 69% against Abeta42-induced neurotoxicity and 73% against H(2)O(2)-induced cytotoxicity in PC12 cell culture at 40 muM final concentration. At the same concentration, scopoletin inhibited Abeta42 fibril formation up to 57%. The IC(50) concentration for AChE and BuChE enzyme inhibition by scopoletin was 5.34 and 9.11 muM, respectively. The antiaggregation and enzyme inhibition results were complemented with strong molecular interactions of scopoletin with target proteins validated by in silico molecular docking analysis. Based on this study, it can be concluded that scopoletin can be used as a lead for amelioration of symptoms and disease-modifying effects in AD.