Comprehensive evaluation of AChE inhibition by Eulophia ochreata extract utilizing in silico, ex vivo, and in vivo zebrafish models

Abstract

Dementia commonly accompanies various neurodegenerative conditions, notably Alzheimer’s disease. The pursuit of natural therapies for these diseases and their related symptoms has garnered widespread global interest. The present study aimed to explore the potential of Eulophia ochreata L. extract, containing phenanthrene active compounds, as an acetylcholinesterase (AChE) inhibitor. Analytical techniques confirmed the presence of phenanthrene compounds in the extract, which were then screened for AChE inhibition through molecular docking, ex vivo assays, and scopolamine-induced cognitive deficits in zebrafish larvae. These phenanthrene compounds, found in the extract of Eulophia ochreata L., exhibited a similar affinity for AChE as the standard drug Donepezil, with comparable interactions. Ex vivo assays using zebrafish larvae lysate and mouse brain homogenate indicated dose-dependent AChE inhibition with increasing extract concentrations. Behavioral assessments, including T and Y maze tests, revealed significant cognition improvement in extract-treated larvae having scopolamine-induced cognitive dysfunction, particularly at 1.3 µg/mL concentration. The combined results from molecular docking, ex vivo assays, and in vivo cognition deficit models underscored the potential of Eulophia ochreata L. extract as an AChE inhibitor, suggesting its phytochemicals could hold therapeutic promise, indicating further validation in mammalian models for translation into clinical therapies.