title: Rosmarinic acid protects rat hippocampal neurons from cerebral ischemia/reperfusion injury via the Akt/JNK3/caspase-3 signaling pathway.
abstract: Cerebral ischemia/reperfusion injury can result in neuronal death, which further results in brain damage and can even lead to death. Although recent studies showed that rosmarinic acid (RA) exerts neuroprotective effects and attenuates ischemia-induced brain injury and neuronal cell death, little is known about the precise mechanisms that occur during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to examine the underlying mechanism of the neuroprotective effects of RA against ischemic brain injury induced by cerebral I/R. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. We randomly divided rats into five groups: sham, I/R, I/R+RA, I/R+Vehicle and I/R+RA+LY. Open-field, closed-field and Morris water maze tests were carried our separately to examine the anxiety and cognitive behavior of each group. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. The levels of p-Akt, p-JNK3 and cleaved caspase-3 in the hippocampus were also examined by Western blotting. Our results showed that administration of RA protected locomotive ability, relieved anxiety behavior and protected cognitive ability in cerebral I/R-injured rats. Additionally, RA significantly protected neurons in the hippocampal CA1 region against cerebral I/R-induced damage. Furthermore, RA increased the phosphorylation of Akt1, downregulated the phosphorylation of JNK3 and reduced the expression of cleaved caspase-3. Finally, the Akt inhibitor LY294002 reversed all the protective effects of RA, indicating that RA protects neurons in the hippocampal CA1 region from ischemic damage through the Akt/JNK3/caspase-3 signaling pathway.
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, PR China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, PR China. Electronic address: sdyanhui@21cn.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000523:psychology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D053630:Depsides / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000523:psychology; D000097123:Rosmarinic Acid
chemical_list: D053148:Caspase 3; D002934:Cinnamates; D053630:Depsides; D048057:Mitogen-Activated Protein Kinase 10; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D000097123:Rosmarinic Acid; C494920:Akt1 protein, rat; C505410:Casp3 protein, rat
keywords: Akt; Caspase-3; Cerebral ischemia; JNK3; Rosmarinic acid