Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2.
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.
El Omri
Abdelfatteh
A
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Han
Junkyu
J
Yamada
Parida
P
Kawada
Kiyokazu
K
Ben Abdrabbah
Manef
M
Isoda
Hiroko
H
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
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