Protective effects of Gamma-decanolactone against PTZ-induced behavioral alterations in Caenorhabditis elegans: behavioral and In Silico evidence.

Gamma-decanolactone (GD) was found to exert neuroprotective and anticonvulsant effects in seizure rodent models induced by pentylenetetrazol (PTZ), although mechanisms of action remain to be determined. The aim of this study was to investigate GD-initiated (1) behavioral effects (2) protective activity against PTZ-induced paralysis in Caenorhabditis elegans, and (3) interaction with GABAergic system utilizing in silico analyses. Molecular docking demonstrated favorable binding energies between GD and key GABAergic proteins in C. elegans, including unc-25 (encodes glutamic acid decarboxylase), unc-47 (encodes the vesicular GABA transporter), and unc-49 (encodes the ionotropic GABA receptor subunit), with the strongest interaction observed for unc-47. Docking studies with human GABA(A) receptor subunits also indicated compatible binding within conserved receptor cavities. In mutant worms unc-29(e193) I, GD reduced body bends after pre-treatment, although this effect was reversed after 48 h. GD also diminished pharyngeal pumping in the cca-1(ad1650) X strain, but not wild-type N2 animals. Importantly, GD significantly decreased PTZ-induced paralysis in wild-type worms in a dose-dependent manner after 24 or 48 h. However, no marked protective effect was detected in mutant strains lacking unc-25, unc-47, or unc-49, suggesting that the anticonvulsant effects of GD appear to depend upon intact GABAergic signaling pathways.