title: Ferulic acid attenuates the down-regulation of MEK/ERK/p90RSK signaling pathway in focal cerebral ischemic injury.
abstract: Ferulic acid provides neuroprotective effects against a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia. Mitogen-activated protein kinases can regulate extensive intracellular processes including cell differentiation, growth, and death. This study further investigated whether ferulic acid modulates a protective mechanism through the activation of Raf-MEK-ERK and its downstream targets, including 90 ribosomal S6 kinase (p90RSK) and Bad during cerebral ischemic injury. Male Sprague-Dawley rats were treated with ferulic acid (100mg/kg) or vehicle after the onset of MCAO and brain tissues were collected 24h after MCAO. These results indicated that ferulic acid decreases the volume of the infarct area and the number of cells positive in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Although MCAO injury induces a decrease in the phosphorylation of Raf-1, MEK1/2, and ERK1/2, ferulic acid treatment prevents the injury-induced decrease in these phosphorylation levels. Ferulic acid also attenuates the injury-induced decrease in p90RSK and Bad phosphorylation levels. These findings suggest that ferulic acid prevents MCAO-induced neuronal cell death and that the MEK-ERK-p90RSK-Bad signaling pathway is involved in these neuroprotective effects.
authors.affiliation: Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea. Electronic address: pokoh@gnu.ac.kr.
authors.forename: Phil-Ok
authors.initials: PO
authors.lastname: Koh
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D003373:Coumaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D003373:Coumaric Acids; D018696:Neuroprotective Agents; C004999:ferulic acid; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2
keywords: Brain ischemia; Ferulic acid; MAP kinase