Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 708, Issue 1-3, Pages 44-55Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2013.02.041
Keywords
Berberine; Cell cycle arrest; Cell survival; Cerebral ischemia and reperfusion
Categories
Funding
- National Natural Science Foundation of China [81073092, 90713043, 30801523]
- National S&T Major Special Project for New Drug R&D Program of China [2012ZX09103-201-041, 2011ZX09101- 002-11, 2012ZX09102-201-008]
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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. (C) 2013 Elsevier B.V. All rights reserved.
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