Ameliorative Effect of Polypodium vulgare L. Rhizome on Anxiety and Depressive-Like Behaviors in Restraint-Subjected Mice: Involvement of Inflammatory, Oxidative and Apoptotic Pathways

Background: Developing drugs with higher efficacy and fewer side effects for psychological disorders has always been of interest. The rhizome of Polypodium vulgare L. (common polypody) has been used as a mood stabilizer in Persian Medicine (PM). Objectives: The present study evaluates the anxiolytic and antidepressant effects of the hydroethanolic extract of common polypody rhizome (PEE) and the possible underlying mechanisms in mice subjected to chronic restraint stress (CRS). Methods: Sixty NMRI male mice were exposed to CRS and received either a vehicle, fluoxetine, or PEE (at doses of 250, 500, 1000, and 1500 mg.kg(-1)). The forced swim test (FST), tail suspension test (TST), open-field test (OFT), and elevated-plus maze (EPM) were conducted to evaluate depressive-like and anxiety-like behavior. Oxidative, inflammatory, and apoptotic markers, as well as brain-derived neurotrophic factor (BDNF), were measured in the prefrontal cortex (PFC) and hippocampus (HIP). Corticosterone levels were also assessed in serum samples. Results: Polypody rhizome increased the time spent in the central zone of the OFT, as well as the time spent and the number of entries into the open arms of the EPM, while it decreased the immobility time in the FST and TST. Administration of PEE caused a significant decline in serum levels of corticosterone, as well as tissue levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and malondialdehyde (MDA). Additionally, it increased superoxide dismutase (SOD) activity in the PFC and HIP. Polypody rhizome also significantly restored total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity, and BDNF expression in the HIP. Moreover, Bcl-2 levels increased in the PFC, and Bax and caspase-3 expressions were downregulated in both regions with PEE administration. Conclusions: Polypody rhizome exerted anxiolytic and antidepressant effects in behavioral tests and reversed CRS-induced oxidative, inflammatory, and apoptotic alterations.