Isothiocyanate-Rich Essential Oil of Morisonia flexuosa L. Exhibits Anxiolytic-like Effects That May Involve Serotonergic Pathways in Zebrafish

Anxiety disorders are characterized by dysregulation of monoaminergic signaling and remain a significant therapeutic challenge due to limitations associated with current pharmacological treatments. In this context, the essential oil of Morisonia flexuosa (Capparaceae) seeds was chemically characterized and evaluated for anxiolytic-like activity in adult zebrafish. Chemical profiling by GC–MS and GC–FID revealed a predominance of isothiocyanates, particularly butyl isothiocyanate (42.60%) and isobutyl isothiocyanate (42.28%). Acute toxicity assessment demonstrated no lethality at the tested doses. Behavioral analyses showed a significant increase in light preference in the light/dark paradigm, with moderate locomotor reduction insufficient to account for the behavioral shift solely by sedation. Pharmacological antagonism assays indicated that the anxiolytic-like effect was predominantly mediated by 5-HT1 and 5-HT2A/2C receptors. Chemometric analyses (PCA, HCA, and heatmap) revealed statistical association between compound abundance and behavioral endpoints, supporting the contribution of major isothiocyanates within the tested model. Notably, the strongest behavioral response was observed at the lowest concentration, suggesting an ideal effective concentration range. Collectively, these findings provide the first evidence that an isothiocyanate-rich essential oil from M. flexuosa exerts serotonergic-involved anxiolytic-like effects in zebrafish and supports further mechanistic investigation of its neuropharmacological potential.