Effects of <i>Ruta graveolens</i> L. on Locomotor Disorders and Anxiety: Modulation of Hippocampal Antioxidant Capacity

Background and aims: Ruta graveolens L. has shown promise in alleviating anxiety and enhancing motor balance, attributed to its antioxidant properties. This plant is rich in flavonoids, such as rutin, which aid in mitigating oxidative stress—a condition associated with anxiety and locomotor disorders. Research indicates that its neuroactive compounds may contribute to the maintenance of neural function and the restoration of balance. Methods: This study involved 56 eight-week-old male Balb/c mice divided into seven groups. The control group received normal saline (NS) intraperitoneally for five days without cold stress. Three extract groups were subjected to cold stress and administered Ruta graveolens L. extract (RGE) at doses of 30, 100, and 300 mg/kg. Another NS group also faced cold stress but received NS. The diazepam group received 1 mg/kg diazepam intraperitoneally under cold stress. The seventh group received 300 mg/kg RGE after flumazenil (3 mg/kg) administration. Anxiety levels were assessed using the elevated plus maze (EPM), and psychomotor coordination was evaluated with the rotarod test. Following deep anesthesia with ketamine and xylazine, blood samples were collected, and the hippocampi were extracted for biochemical analyses of antioxidant capacity and malondialdehyde (MDA) levels. Results: Cold stress significantly decreased both the number of entries into and the duration of time spent in the open arm of the EPM (P &lt; 0.001). Locomotor coordination in the NaCl group exposed to cold stress was diminished compared to the control group. Administration of RGE at all three doses improved locomotor coordination and balance movements. Furthermore, the extract at all doses enhanced the antioxidant capacity of the hippocampus and increased the duration of time spent in the open arm. Conclusion: RGE effectively reduced anxiety, improved balance, and enhanced the antioxidant capacity of the hippocampus.