Anxiolytic and Antidepressant-like Effects of Desmodium triflorum Extract Against Chronic Restraint Stress in Wistar Rats: Behavioral, Neurochemical, and Antioxidant Evidence

Abstract

Background: Anxiety and depression are among the most prevalent psychiatric disorders worldwide and are associated with dysregulation of monoaminergic neurotransmission, hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and oxidative stress. Conventional pharmacotherapies, including benzodiazepines and tricyclic antidepressants, are limited by dependence, withdrawal effects, and poor long-term tolerability, highlighting the need for safer plant-derived alternatives such as Desmodium triflorum.

Objective: This study evaluated the anxiolytic and antidepressant-like potential of aqueous Desmodium triflorum extract in a chronic restraint stress (CRS) model in Wistar rats and investigated the neurochemical, neuroendocrine, and antioxidant mechanisms underlying its effects.

Methods: Adult Wistar rats were exposed to 3 h of daily immobilization stress for 30 days and treated with vehicle, Desmodium triflorum extract (400 or 800 mg/kg BW, orally), diazepam (2 mg/kg), or imipramine (15 mg/kg). Behavioral assessments included the elevated plus-maze, forced swim, and open field tests. Blood cortisol, brain dopamine (DA), serotonin (5-HT), oxidative stress markers, and hepatic histopathology were evaluated.

Results: CRS induced significant anxiety- and depressive-like behaviors, elevated cortisol, altered cortical and hippocampal DA and 5-HT levels, and reduced antioxidant defenses. Desmodium triflorum extract produced dose-dependent improvements, with the 800 mg/kg dose significantly increasing open-arm exploration, reducing immobility, lowering cortisol, restoring monoamine levels, and enhancing glutathione, superoxide dismutase, and catalase activities. Hepatic histopathology showed no treatment-related abnormalities.

Conclusion: Aqueous Desmodium triflorum extract exerts dose-dependent anxiolytic and antidepressant-like effects through monoaminergic modulation, HPA-axis normalization, and antioxidant restoration, with a favorable hepatic safety profile. These findings support further mechanistic and translational investigation of Desmodium triflorum as a potential phytotherapeutic for stress-related psychiatric disorders.