Antidepressant‐ and Anxiolytic‐Like Effect of the Froriepia subpinnata Extract in the Rat: Neurochemical Correlates

ABSTRACT Background The study aims to explore the potential antianxiety effect of Froriepia subpinnata, a native plant in northern Iran, and it is considered an antiflatulent, appetizing, antiseptic, antispasmodic, and diuretic. Despite its widespread use in diets and its reputation for calming effects, no prior research has specifically investigated its antianxiety properties. Methods Rats were subjected to a variety of stressors for 24 days. Rats were treated with the F. subpinnata extract (100, 200, and 400 mg/kg, orally) for 14 days starting from the 10th day of stress. Then behavioral tests (elevated plus‐maze, open field, sucrose preference, Morris water maze, passive avoidance) were examined. Real‐time PCR was used to investigate changes in the expression of candidate genes of stress response and memory. Oxidative stress markers and corticosterone levels in serum were also measured. Results Chronic stress reduced performance in a variety of tests of anxiety and memory, and treatment with the F. subpinnata extract dose‐dependently improved the behavioral deficits caused by chronic stress. At the dose of 200 mg/kg, the F. subpinnata extract mitigated the effect of stress on the expression of several genes, such as those encoding dopamine D1 and D2 receptors, glutamate NMDA, and AMPA receptor subunits (Grin1 and Gria1, respectively), glucocorticoid and mineralocorticoid receptors, cholecystokinin (CCK) and CCKB receptor, neuropeptide Y, and the GABAA receptor alpha2 subunit. Also, the expression of two genes, TrkB and BDNF, was significantly affected by the extract, demonstrating meaningful decreasing changes. Furthermore, treatment with the extract led to a decrease in oxidative stress and an elevation in cortisol levels in stressed animals. Conclusion In this study, we provide the first evidence of the antistress and antianxiety effects of F. subpinnata extract, along with its potential procognitive impact on memory. The potential antianxiety and antidepressant effects of Froriepia subpinnata were explored. Behavioral tests, including the elevated plus‐maze, open field, sucrose preference, Morris water maze, and passive avoidance, were conducted. Real‐time PCR was employed to examine changes in the expression of candidate genes associated with stress response and memory. Oxidative stress markers and corticosterone levels in serum were measured.