Archives of Pharmacal Research

, Volume 38, Issue 12, pp 2241–2250 | Cite as

Neuroprotective effect of phytoceramide against transient focal ischemia-induced brain damage in rats

  • Hong Kyu Lee
  • Ji Yeon Jang
  • Hwan-Su Yoo
  • Yeon Hee SeongEmail author
Research Article


The present study was conducted to investigate the protective effect of phytoceramide against focal transient ischemic brain damage and the underlying mechanisms. Focal transient ischemic brain damage was produced in rats by occlusion of the middle cerebral artery for 2 h followed by 24 h of reperfusion (MCAO/reperfusion). Orally administered phytoceramide (10, 25, and 50 mg/kg) significantly reduced MCAO/reperfusion-induced brain infarction and edema as well as the development of behavioral disabilities in the animals. Depletion of glutathione levels and lipid peroxidation in brain tissue following MCAO/reperfusion was reduced by administration of phytoceramide. The expressions of phosphorylated extracellular signaling-regulating kinases/mitogen-activated protein kinase (p-ERK1/2 MAPK), inflammatory factors such as cyclooxygenase-2 and inducible nitric oxide synthase, and pro-apoptotic proteins Bax and caspase-3 were increased while the anti-apoptotic protein Bcl-2 was decreased in ischemic brain; these effects were significantly inhibited by treatment with phytoceramide. Furthermore, phytoceramide activated the phosphatidylinositol 3′-kinase (PI3K)/Akt pathway to prevent ischemic brain damage. These results suggest that phytoceramide may help prevent neurodegeneration caused by ischemic stroke due to its anti-oxidant, anti-apoptotic, and anti-inflammatory properties.


Phytoceramide Ischemic stroke MCAO/reperfusion Neuroprotection Apoptosis Neuroinflammation 



This work was supported by National Research Foundation of Korea Grant funded by the Korean Government (2012-0014760).

Compliance with ethical standards

Conflict of interest

Authors declare that they have no competing interests.


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Copyright information

© The Pharmaceutical Society of Korea 2015

Authors and Affiliations

  • Hong Kyu Lee
    • 1
  • Ji Yeon Jang
    • 1
  • Hwan-Su Yoo
    • 2
  • Yeon Hee Seong
    • 1
    Email author
  1. 1.College of Veterinary MedicineChungbuk National UniversityCheongjuRepublic of Korea
  2. 2.College of PharmacyChungbuk National UniversityCheongjuRepublic of Korea

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