Antidepressant-like effects of rosmarinic acid through mitogen-activated protein kinase phosphatase-1 and brain-derived neurotrophic factor modulation

Rosmarinic acid (RA) is one of the major bioactive compounds of Rosmarinus officinalis, a culinary and edible aromatic plant and was demonstrated to have several neuroprotective properties including anti-depressive-like effect. The current study was designed to contribute to understanding the molecular mechanism of RA beneficial effects in tail suspension test (TST)-induced depression in mice with bupropion as positive control, and mice without TST as negative control. Changes in serum corticosterone (CORT) level and cerebrum level of catecholamines: dopamine (DOP), noradrenaline (NAD), and adrenaline (ADR) were investigated. Moreover, brain-derived neurotrophic factor (Bdnf), mitogen-activated protein kinase phosphatase-1 (Mkp-1), tyrosine hydroxylase (Th) and pyruvate carboxylase (Pc) gene expression in mice cerebrum were investigated using real-time PCR. RA was demonstrated to show anti-depressant-like effect by significant reduction of immobility time in the TST in mice. This effect was accompanied by a downregulation of Mkp-1 to reach the unstressed group level, an upregulation of Bdnf, Th and Pc in the limbic system. Furthermore, RA significantly decreased serum corticosterone level and increased dopamine level in the limbic system in mice brain. Our study provides the first evidence that RA has anti-depressant activity via downregulation of Mkp-1, upregulation of Bdnf and modulation of dopamine and corticosterone synthesis.