title: Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation.
abstract: Rosmarinus officinalis (R. officinalis), a culinary aromatic and medicinal plant, is very rich in polyphenols and flavonoids with high antioxidant properties. This plant was reported to exert multiple benefits for neuronal system and alleviate mood disorder. In our previous study, we demonstrated that R. officinalis and its active compounds, luteolin (Lut), carnosic acid (CA), and rosmarinic acid (RA), exhibited neurotrophic effects and improved cholinergic functions in PC12 cells in correlation with mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway. The current study was conducted to evaluate and understand the anti-depressant effect of R. officinalis using tail suspension test (TST) in ICR mice and PC12 cells as in vitro neuronal model. Proteomics analysis of PC12 cells treated with R. officinalis polyphenols (ROP) Lut, CA, and RA revealed a significant upregulation of tyrosine hydroxylase (TH) and pyruvate carboxylase (PC) two major genes involved in dopaminergic, serotonergic and GABAergic pathway regulations. Moreover, ROP were demonstrated to protect neuronal cells against corticosterone-induced toxicity. These results were concordant with decreasing immobility time in TST and regulation of several neurotransmitters (dopamine, norepinephrine, serotonin and acetylcholine) and gene expression in mice brain like TH, PC and MAPK phosphatase (MKP-1). To the best of our knowledge this is the first evidence to contribute to the understanding of molecular mechanism behind the anti-depressant effect of R. officinalis and its major active compounds.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Abdelfatteh
authors.initials: A
authors.lastname: El Omri
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondo
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
mesh_terms: D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D053630:Depsides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D027542:Rosmarinus; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000097123:Rosmarinic Acid
chemical_list: D045784:Abietanes; D000928:Antidepressive Agents; D002934:Cinnamates; D053630:Depsides; D010936:Plant Extracts; D011766:Pyruvate Carboxylase; D014446:Tyrosine 3-Monooxygenase; D000097123:Rosmarinic Acid; C018381:salvin