title: Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2.
abstract: OBJECTIVE
  This paper aimed to elucidate the traditional use of Rosmarinus officinalis through the investigation of cholinergic activities and neuronal differentiation in rat pheochromocytoma PC12 cells. These effects were examined in relation to the plant's habitat, the extraction procedure, and the major active compounds of R. officinalis.
  
  
  METHODS
  Cell viability, cell differentiation, acetylcholinesterase (AChE) activity, total choline, acetylcholine (ACh) and extracellular signal-regulated kinases (ERK1/2) were determined in PC12 cells treated with extracts and HPLC-identified polyphenols of R. officinalis originated from Tunisian semi-arid and subhumid area in comparison with nerve growth factor (NGF).
  
  
  RESULTS
  R. officinalis extracts potentiated cell differentiation and significantly enhanced AChE activity in PC12 cells. The highest AChE activity was induced by semi-arid hydro-ethanolic extract (137% of control). Among HPLC-identified and screened polyphenols, carnosic acid (CA) and rosmarinic acid (RA) significantly induced cell differentiation, increased ACh level, and enhanced AChE activity in PC12 cells. U0126, inhibitor of ERK1/2, significantly reduced CA and RA effects on cell differentiation and AChE activity.
  
  
  CONCLUSIONS
  R. officinalis' CA and RA exhibited neurotrophic effects in PC12 cells through cell differentiation induction and cholinergic activities enhancement. These effects could be regulated by mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
authors.forename: Abdelfatteh
authors.initials: A
authors.lastname: El Omri
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Parida
authors.initials: P
authors.lastname: Yamada
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Kawada
authors.forename: Manef
authors.initials: M
authors.lastname: Ben Abdrabbah
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
mesh_terms: D045784:Abietanes / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D018678:Cholinergic Agents / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology; D053630:Depsides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D027542:Rosmarinus / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D000097123:Rosmarinic Acid
chemical_list: D045784:Abietanes; D000110:Acetylcholinesterase; D002070:Butadienes; D018678:Cholinergic Agents; D002934:Cinnamates; D053630:Depsides; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D009570:Nitriles; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D000097123:Rosmarinic Acid; C113580:U 0126; C018381:salvin