Assessment of the molecular mechanism in fish using eugenol as anesthesia based on network pharmacology.

Abstract

Eugenol is a commonly used fish anesthetic, but its mechanism of action is not fully understood. This study employed network pharmacology, molecular docking, and molecular dynamics simulation to explore the anesthetic targets of eugenol in fish. Initially, 63 potential targets for eugenol anesthesia were identified using databases such as SwissTarget, TargetNet, GeneCards, OMIM, and TTD. The DAVID database was utilized to analyze the GO functions and KEGG pathways of these targets, revealing 384 GO enrichment terms and 43 KEGG pathways. These terms involved neuroactive ligand-receptor interaction, calcium signaling pathway, and synaptic transmission. Subsequently, AutodockTools software facilitated molecular docking with targets in the KEGG pathway for "neuroactive ligand-receptor interaction." The results showed that eugenol had a strong affinity with these proteins. Concurrently, molecular dynamics simulations were conducted on the proteins with the top four lowest binding energies (Cnr1, Oprk1, Nr3c1, and Chrm5a) in the presence of eugenol. The eugenol-protein complexes remained stable and equilibrated within the dynamic environment. The results indicated that eugenol-anesthesia might affect membrane receptors, neurotransmitters, and ion signaling. This study elucidates the anesthetic mechanism of eugenol, enriches the primary data on fish anesthesia, and offers new analytical tools for understanding the action mechanisms of fishery drugs.