Effect of Echium amoenum Hydroalcoholic Extract on Restraint Stress-induced Depressive- and Anxiety-like Behaviors in Mice

Abstract

Abstract Introduction: Depression is a threatening disease. Due to adverse effects of chemical antidepressant drugs, researcher’s attention has been shifted toward natural drug. Objective: This study was designed to investigate the effect of Echium amoenum (E. amoenum) treatment on anxiety- and- depressive-like behaviors as well as neuroinflammation and hepatotoxicity markers in restraint stress (RS)-subjectedmice. Methods: Phytochemical properties of E. amoenum extract analyzedby evaluation of total phenolic, flavonoid, rosmarinic acid levels and radical scavenging activity. For behavioral studies, animals were randomly assigned into five groups as follows: control, RS, RS+E75, RS+E150, and RS+E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups were received different doses of E. amoenum (75, 150, and 300 mg/kg, P.O.) concomitantly with RS exposure. At the end of the period, behavioral tests were used to evaluate depression and anxiety.Moreover tissue samples from the prefrontal (PFC), hippocampus (HIP) and liver were performed to assess protein expressions of NF-κB, TNF-α, IL-1β, and IL-6) and liver histology and blood samples for the evaluation of corticosterone, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alanine phosphatase (ALP). Findings: E. amoenum increased percentage of presence in the central area of the Open Field Test, percentage of frequencies and spent time in open arms of Elevated Plus Maze. Also it decreased the immobilization time in the Tail Suspension and Forced Swimming Tests. These results were accompanied by decreased serum corticosterone levels. Furthermore, E. amoenum decreased protein expression of neuroinflammatory markers in the HIP and PFC subregions. Although RS slightly increased serum levels of liver injury markers, no histopathological changes were seen in the RS or E. amoenum-treated groups. Conclusion: These findings suggest that E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated biochemical and behavioral changes. Keywords: Restraint stress, Anxiety, Depression, Neuroinflammation, Echium amoenum, Corticosterone,