Hallmarks of Alzheimer’s disease (AD) pathology include acetylcholine deficiency and plaque deposition. Emerging studies suggest that acetylcholinesterase (AChE) may interact with amyloid beta (Aβ) to promote aggregation of insoluble amyloid beta plaques in brains of patients. Current therapeutic options available for AD patients, such as AChE inhibitors, provide only symptomatic relief. In this study, we screened four natural compounds believed to harbour cognitive benefits- curcumin, piperine, bacoside A and chebulinic acid. In the first section, preliminary screening through computational molecular docking simulations gauged the suitability of the compounds as novel AChE inhibitors. From here, only compounds that met the in silico selection criteria were selected for the second section through in vitro investigations, including AChE enzyme inhibition assay, MTT assay, ThT assay and biochemical analysis via a neuronal cell line model. Of the four compounds screened, only curcumin (-9.6kcal/mol) and piperine (-10.5kcal/mol) showed favorable binding affinities and interactions towards AChE and were hence selected. In vitro AChE inhibition demonstrated that combination of curcumin and piperine showed greater AChE inhibition with an IC50 of 62.81 ± 0.01μg/mL as compared to individual compounds, i.e., IC50 of curcumin at 134.5 ± 0.06µg/mL and IC50 of piperine at 76.6 ± 0.08µg/mL. In SH-SY5Y cell model, this combination preserved cell viability up to 85%, indicating that the compounds protect against Aβ-induced neuronal damage (p

Read Full Article (External Site)