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 cognition deficits in zebra fish larvae. Analytical techniques confirmed the phenanthrene compounds within the extract of Eulophia ochreata L.,exhibiting similar affinity to AChE as the standard drug donepezil, with comparable interactions. Ex vivo assays using zebra fish 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 these into clinical therapies.