Archives of Pharmacal Research

, Volume 40, Issue 6, pp 760–771 | Cite as

Phytoceramide ameliorates ß-amyloid protein-induced memory impairment and neuronal death in mice

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


The present study was performed to investigate the protective effect of phytoceramide against ß-amyloid protein (Aβ) (25–35)-induced memory impairment and its underlying mechanisms in mice. Memory impairment in mice was induced by intracerebroventricular injection of 15 nmol Aβ (25–35) and measured by the passive avoidance test and Morris water maze test. Chronic administration of phytoceramide (10, 25 and 50 mg/kg, p.o.) resulted in significantly less Aβ (25–35)-induced memory loss and hippocampal neuronal death in treated mice compared to controls. The decrease of glutathione level and increase of lipid peroxidation in brain tissue following injection of Aβ (25–35) was reduced by phytoceramide. Alteration of apoptosis-related proteins, increase of inflammatory factors, and phosphorylation of mitogen activated proteins kinases (MAPKs) in Aβ (25–35)-administered mice hippocampus were inhibited by phytoceramide. Phosphatidylinositol 3′-kinase (PI3K)/Akt pathway and phosphorylation of cyclic AMP response element-binding protein (CREB) were suppressed, while phosphorylation of tau (p-tau) was increased in Aß (25–35)-treated mice brain; these effects were significantly inhibited by administration of phytoceramide. These results suggest that phytoceramide has a possible therapeutic role in managing cognitive impairment associated with Alzheimer’s disease. The underlying mechanism might involve inhibition of p-tau formation via anti-apoptosis and anti-inflammation activity and promotion of PI3K/Akt/CREB signaling process.


Phytoceramide Alzheimer’s disease β-amyloid protein (25–35) Memory impairment Neuroprotection 



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

The authors declare that there are no conflicts of interest.


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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  1. 1.College of Veterinary Medicine and Veterinary Medical CenterChungbuk National UniversityCheongjuRepublic of Korea
  2. 2.College of PharmacyChungbuk National UniversityCheongjuRepublic of Korea

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