Anxiolytic-like effects of orientin in mice: behavioral and neurochemical investigations

Purpose: Orientin, a water-soluble flavonoid C-glycoside found in various medicinal plants, exhibits diverse pharmacological properties. This study aimed to evaluate its anxiolytic-like effects in mice and to explore the potential roles of adrenergic, serotonergic, and GABAergic neurotransmitter systems in mediating these effects. Materials and Methods: Orientin was administered intraperitoneally to mice at 20, 40, or 80 mg/kg. Anxiolytic-like effects were assessed using the light–dark box, elevated plus maze, hole-board, and open-field tests. For mechanism studies, separate groups received α₂-adrenergic antagonist yohimbine (5 mg/kg), 5-HT1A antagonist WAY-100635 (1 mg/kg), or GABAA antagonist flumazenil (3 mg/kg) prior to 20 mg/kg orientin. Results: Orientin at 20 mg/kg elicited significant anxiolytic-like effects in the hole-board, light–dark box, and open-field tests. The 40 mg/kg dose produced a significant effect only in the hole-board test, whereas the 80 mg/kg dose failed to elicit significant changes in any behavioral paradigm. The pronounced efficacy observed at 20 mg/kg suggests a bell-shaped dose–response profile. Pretreatment with α₂-adrenergic, 5-HT1A serotonergic, or GABAA receptor antagonists partially or completely attenuated the effects of orientin, with the degree of reversal varying among the behavioral assays. Conclusion: The present findings provide compelling evidence that orientin exerts anxiolytic-like effects, potentially mediated via α₂-adrenergic, 5-HT1A serotonergic, and GABAA receptor pathways.