In silico and in vitro Approach To Identify Memory Enhancers from Sida rhombifolia L.

Abstract

<p style="text-align: justify;"><strong>Background: </strong><em>Sida rhombifolia </em>L. is a well documented Ayurvedic medicine for the management of neurodegenerative diseases and to enhance cognitive function. Researchers demonstrated its activities under various animal model/s, but lack the probable molecular mechanism in the treatment of Alzheimer&rsquo;s disease. Current study was aimed to identify the acetylcholinesterase (AChE) inhibitory potency of phytocompounds and enriched fractions from <em>S.rhombifolia </em>using <em>in vitro</em> and network pharmacology approaches.<em> </em><strong>Methods:</strong> Phytocompounds were retrieved from phytochemical databases, scientific reports and quired for druggability. Protein targets were predicted using BindingDB (<em>p</em>&ge;0.7). STRING database and KEGG pathway were utilized to perform gene set enrichment analysis and to identify the probable pathways modulated by the phytocompounds. Cytoscape v3.6.1 was used to construct a target-compound-pathway network. Docking was performed by PyRx 0.8v. Enriched fractions of <em>S. rhombifolia</em> were tested for <em>in vitro </em>AChE inhibitory potency using the AChE enzyme.<strong> Results: </strong>Among 35 compounds, 26 compounds showed positive drug likeness property. Out of 26 compounds, 9 compounds i.e. 2D-hydroxyecdysone, ecdysone, pterosterone-3-O-&beta;-D-glucopyranoside, acacetin, kaempferol, sanguinine, vascicine, vasicinol, vasicinone were predicted to target AChE and other 9 therapeutic targets involved in Alzheimer&rsquo;s disease (AD). Acacetin scored lowest binding energy with AChE (-8.9kcal/mol). Among the selected enriched fractions, hexane fraction pertains highest AChE inhibition (IC₅₀ 12.87&mu;g/ml) compared to clinical approved drug Donepezil (IC₅₀2.92&mu;g/ml).<strong> Conclusion: </strong>The role of <em>S.rhombifolia</em> for the management of AD could be attributed due to the major effect of 2D-hydroxyecdysone, ecdysone, pterosterone-3-O-&beta;-Dglucopyranoside, acacetin, kaempferol, sanguinine, vascicine, vasicinol, vasicinone on AChEand their action on multiple protein molecules associated with AD pathogenesis. <strong>Key words:</strong> Alzheimer&rsquo;s disease, Acacetin, Acetylcholinesterase, In silico docking, Network pharmacology, Sida rhombifolia, Sangunine.