Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt

• Published in: European journal of pharmacology 2013-05, Vol.708 (1-3), p.44-55
• Main Authors: Chai, Yu-Shuang, Hu, Jun, Lei, Fan, Wang, Yu-Gang, Yuan, Zhi-Yi, Lu, Xi, Wang, Xin-Pei, Du, Feng, Zhang, Dong, Xing, Dong-Ming, Du, Li-Jun
• Format: Article
• Language: English
• Subjects: Animals; Berberine; Berberine - pharmacology; Brain Ischemia - metabolism; carotid arteries; caspases; cell cycle; Cell cycle arrest; Cell Cycle Checkpoints - drug effects; Cell survival; Cell Survival - drug effects; cell viability; Cells, Cultured; Cerebral ischemia and reperfusion; Cyclin D1 - genetics; Cyclin D1 - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; ischemia; Male; medicine; Mice; Mice, Inbred ICR; mitogen-activated protein kinase; neurons; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; PC12 Cells; pharmacology; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; phosphorylation; protective effect; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Reperfusion Injury - metabolism; RNA, Messenger - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.02.041

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. [Display omitted]