title: Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt.
abstract: Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury.
authors.affiliation: Protein Science Laboratory of the Ministry of Education, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yu-Shuang
authors.initials: YS
authors.lastname: Chai
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Fan
authors.initials: F
authors.lastname: Lei
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wang
authors.forename: Zhi-Yi
authors.initials: ZY
authors.lastname: Yuan
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Xin-Pei
authors.initials: XP
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Xing
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Du
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D001599:Berberine; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt