Melissa officinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis.

What is the central question of this study? Prolonged stress exposure induces detrimental changes in the brain structure, and increases the vulnerability to develop psychiatric disorders. The central question of this study is how Melissa officinalis L. ameliorates anxiety- and depressive-like behavior of mice. What is the main finding and its importance? Melissa officinalis L. possessed anxiolytic and anti-depressant effects, which could mainly mediate through its antioxidant and anti-apoptotic properties.Objective This study evaluated the effects of hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviors, oxidative stress, and apoptosis markers in the restraint-stress exposed mice. Methods In order to induce depression-like model, mice were subjected to restraint-stress (3 h day for 14 days) and received normal saline or HAEMO (50, 75, and 150 mg kg  day ) for 14 days. The administered doses of HAEMO were designated based on one the main phenolic compounds present in the extract, rosmarinic acid (RA), concentration (2.55 mg kg at lowest dose), other phytochemical analysis including assays for antioxidant activity, total phenols, and flavonoids contents were also carried out. The behavioral changes in the open field task, elevated plus maze, tail suspension, and forced swimming tests were evaluated. Also, malondialdehyde (MDA) levels and enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and total antioxidant capacity were assessed in the prefrontal cortex (PFC) and hippocampus (HIP). Moreover, levels of Bcl-2, Bax, and caspase 3, in the brain as well as serum concentration of corticosterone (CORT), were evaluated. Results HAEMO (75 and 150 mg kg ) significantly reversed anxiety- and depressive-like behaviors. Also, the HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities, and restored serum levels of CORT. The immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the PFC and HIP of restraint-stress exposed mice. Conclusion Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice. This article is protected by copyright. All rights reserved.