The Protective Effect of Hydroalcoholic Extract of the Southern Maidenhair Fern (Adiantum capillus-veneris) on the Depression and Anxiety Caused by Chronic Stress in Adult Male Mice: An Experimental Randomized Study

Antioxidant compounds are novel approaches in the treatment of neurological disorders. The purpose of this study was to examine the antidepressant and anxiolytic effects of the hydroalcoholic extract of Adiantum capillus-veneris (rich in flavonoids with antioxidant properties) in mice under chronic restraint stress (CRS). This experimental study was conducted in a university-affiliated Experimental Animal Unit, Khuzestan, Iran, from April to June 2018. Forty male Balb/C mice were randomly divided into five groups (n = 8), including under chronic restraint stress (CRS) receiving normal saline, hydroalcoholic extract of A. capillus-veneris (100, 200, and 400 mg/kg/day, i.p), or diazepam (10 mg/kg/day, i.p). After 21 days of the consecutive treatment, anxiolytic and antidepressant activities were evaluated using elevated plus-maze (EPM) and forced swim test (FST). Moreover, serum and brain levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), as well as serum corticosterone, were measured. Immobility time in the FST was significantly decreased (P = 0.002, P = 0.001, P < 0.0001) after treating CRS mice with all doses of the extract. CRS-exposed mice treated with all doses of the extract showed a significantly increased percentage of entries into the open arm (P < 0.0001, P = 0.001) and reduced closed arm entries in the EPM (P = 0.012, P = 0.024). Extract at all doses significantly increased serum (P < 0.0001) and brain (P = 0.011, P = 0.004, P = 0.001) TAC in CRS-exposed mice. The extract (200 and 400 mg/kg) also reduced CRS-induced serum and brain MDA (P < 0.0001, P = 0.001). Serum corticosterone did not significantly change following the extract treatment. A. capillus-veneris extract showed antidepressant and anxiolytic effects by reducing oxidative stress markers.