Abstract

There is a constant demand to develop an effective and affordable new drug entity to manage cognitive impairment. Medicinal herbs serve as natural resources for mining of new drug candidates. We used chemoinformatics to identify the bioactive compounds from Amaranthus tricolor L. a common leafy vegetable and often used in traditional medicine to manage cognitive dysfunction. We carried out a series of bioinformatics studies with the phytoconstituents of Amaranthus tricolor to elicit their possible molecular functions in cognitive disorders including Alzheimer’s disease. We first identified the bioactive phytoconstituents from Amaranthus tricolor and predicted their potential protein targets involved in the pathogenesis of cognitive dysfunction using BindingDB (p≥0.7). Gene ontology functional enrichment analysis was performed using search tool for the retrieval of interacting genes/proteins. The pathways that are probably regulated by the identified plant phytoconstituents were analyzed using Kyoto encyclopedia of genes and genomes. Docking studies were carried out with AutoDock4.2v. Molecular dynamics analyses were performed using Schrodinger Desmond 6.1v software for a 50 ns production run. Thirty nine phytoconstituents were identified in Amaranthus tricolor, five of which were predicted to modulate eight potential protein targets involved in cognitive impairment. Gene ontology functional enrichment analysis revealed twenty eight biological processes and 10 molecular functions associated with cognitive impairment. Kyoto encyclopedia of genes and genomes pathway identified eight pathways that are directly related to cognitive impairment. Serotonergic and cholinergic synapse was identified as key pathways. Kaempferol exhibited the highest binding affinity with acetylcholinesterase, monoamino oxidase A and monoamino oxidase B. Molecular dynamics simulation demonstrated stable intermolecular interactions between kaempferol and acetylcholinesterase. Our study identified flavonoids from Amaranthus tricolor as having benefits in managing cognitive impairment and offers a broader scope to mine for potential drug candidates from this natural resource. Our study was limited to computer simulations and calls for wet lab validation of the predicted molecular functions.