Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway

Xin-yu Liu, Xin-yu Zhou, Jin-cai Hou, Hua Zhu, Zhong Wang, Jian-xun Liu, Yong-qiu Zheng

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

Abstract

Aim: 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. Conclusion: 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.
Original languageEnglish
Pages (from-to)421-428
Number of pages8
JournalActa Pharmacologica Sinica
Volume36
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • cerebral ischemia
  • cerebrovascular disease
  • developmental neurobiology
  • ginsenoside
  • stroke

Fingerprint

Dive into the research topics of 'Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway'. Together they form a unique fingerprint.

Cite this