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

Abstract

21Rosmarinic acid (RA) is one of the major bioactive compounds of Rosmarinus officinalis, a 22 culinary and edible aromatic plant and was demonstrated to have several neuroprotective 23 properties including anti-depressive-like effect. The current study was designed to contribute 24 to understanding the molecular mechanism of RA beneficial effects in tail suspension test 25 (TST)-induced depression in mice with bupropion as positive control, and mice without TST 26 as negative control. Changes in serum corticosterone (CORT) level and cerebrum level of 27 catecholamines: dopamine (DOP), noradrenaline (NAD), and adrenaline (ADR) were 28 investigated. Moreover, brain-derived neutrophic factor (Bdnf), mitogen-activated protein 29 kinase phosphatase-1 (Mkp-1), tyrosine hydroxylase (Th) and pyruvate carboxylase (Pc) gene 30 expression in mice cerebrum were investigated using real-time PCR. RA was demonstrated to 31 show anti-depressant-like effect by significant reduction of immobility time in the TST in 32 mice. This effect was accompanied by a downregulation of Mkp-1 to reach the unstressed 33 group level, an upregulation of Bdnf, Th and Pc in the limbic system. Furthermore, RA 34 significantly decreased serum corticosterone level and increased dopamine level in the limbic 35 system in mice brain.Our study provides the first evidence that RA has anti-depressant activity 36 via downregulation of Mkp-1, upregulation of Bdnf and modulation of dopamine and 37 corticosterone synthesis.38 39

Antidepressant‐Like Effect of Ferulic Acid via Promotion of Energy Metabolism Activity

“…FA (5 mg kg –1 ) was mixed with drinking water and then directly administered by oral gavage with a feeding tube and syringe every day for 7 days. Previously, we performed several animal experiments using CQA derivatives such as 3,5‐diCQA, RA, and 3,4,5‐triCQA . These CQA derivatives showed neuronal activity at the following concentrations: 3,5‐diCQA at 6.7 mg kg –1 ; RA at 5 and 10 mg kg –1 ; and 3,4,5‐triCQA at 5 mg kg –1 .…”

“…Tokyo, Japan) was used as a positive control. It was dissolved in distilled water and orally administered to mice at a volume of 20 mg kg –1 body weight, as reported in previous study …”

“…The brain tissues were isolated, washed with ice‐cold PBS, and immediately immersed in liquid nitrogen. As previous studies have pointed out the functional and structural alterations in the limbic area, including cerebral cortex and amygdala, in mouse models of depression and in adult patients with major depressive disorder, the limbic area of mice brain was focused to determine the mechanisms of anti‐depressant‐like effects of FA. The entire limbic area of the mouse brain containing the cortex, hippocampus, and amygdale was quickly dissected on ice and was minced for RNA extraction.…”

“…Previously, we reported that 3,5‐diCQA and CQA derivatives from purple sweet potato extract had neuroprotective activities. Another CQA derivative rosmarinic acid (RA) showed antidepressant activity . Therefore, FA, as a member of the family of CQA derivatives, is considered to have potential antidepressant‐like activity.…”

Enhanced oral bioavailability and prophylactic effects on oxidative stress and hepatic damage of an oil solution containing a rosmarinic acid–phospholipid complex

“…Rosmarinic acid (RA), a phenolic compound, is an ester of caffeic acid and 3,4-dihydroxyphenyl lactic acid commonly found in various plants from the mint family (Lamiaceae), such as Perilla frutescens, Rosmarinus officinalis, Prunella vulgaris, Ocimum basilicum and other crops (Kondo, Omri, Han, & Isoda, 2015;Lee & Scagel, 2010). These plants are usually used as raw materials in beverage or food flavour sources.…”