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? How does an extract of Melissa officinalis L. ameliorate anxiety- and depressive-like behaviour of mice? What is the main finding and its importance? An extract of Melissa officinalis L. possessed anxiolytic and anti-depressant effects, which could mainly be mediated through its antioxidant and anti-apoptotic properties.This study evaluated the effects of a hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviours, oxidative stress and apoptosis markers in restraint stress-exposed mice. In order to induce a depression-like model, mice were subjected to restraint stress (3 h day-1 for 14 days) and received normal saline or HAEMO (50, 75 and 150 mg kg-1 day-1 ) for 14 days. The administered doses of HAEMO were designated based on the concentration of one of the main phenolic compounds present in the extract, rosmarinic acid (2.55 mg kg-1 at lowest dose); other phytochemical analyses including assays for antioxidant activity, total phenols and flavonoids were also carried out. The behavioural changes in an open field task, elevated plus maze, tail suspension and forced swimming tests were evaluated. Also, malondialdehyde (MDA) levels and enzyme activities of superoxide dismutase and glutathione peroxidase, and total antioxidant capacity were assessed in the prefrontal cortex and hippocampus. Moreover, levels of Bcl-2, Bax and caspase 3 in the brain as well as serum concentration of corticosterone were evaluated. HAEMO (75 and 150 mg kg-1 ) significantly reversed anxiety- and depressive-like behaviours. Also, HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities and restored serum levels of corticosterone. An immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the prefrontal cortex and hippocampus of restraint stress-exposed mice. Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice.