title: Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway.
abstract: OBJECTIVE
  To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI).
  
  
  METHODS
  Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg(-1)·d(-1), ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg(-1)·d(-1), ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting.
  
  
  RESULTS
  Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg(-1)·d(-1)) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 μmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002.
  
  
  CONCLUSIONS
  Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.
authors.affiliation: 1] Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China [2] Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Xin-yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Xin-yu
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Jin-cai
authors.initials: JC
authors.lastname: Hou
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100029, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Jian-xun
authors.initials: JX
authors.lastname: Liu
authors.affiliation: 1] Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China [2] Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Yong-qiu
authors.initials: YQ
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000089662:Doublecortin Protein; D036145:Ginsenosides / Q000737:chemistry / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D005894:Panax / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000089662:Doublecortin Protein; D036145:Ginsenosides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; C000714848:Dcx protein, rat; C049863:ginsenoside Rd
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