title: Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.
abstract: Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway.
authors.affiliation: Department of Pharmacology, Pharmaceutical College, Xianning University, Xianning, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wu
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000627:therapeutic use*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology; D047468:Immunoprecipitation / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009460:Neurologic Examination / Q000379:methods; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
chemical_list: D017304:Annexin A5; D004791:Enzyme Inhibitors; D044950:Flavanones; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C006680:baicalein; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D053148:Caspase 3; C022616:thiazolyl blue; D005947:Glucose