Metabolic Brain Disease

, Volume 34, Issue 1, pp 165–172 | Cite as

Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways

  • Faezeh Rafieipour
  • Elham Hadipour
  • Seyed Ahmad Emami
  • Javad Asili
  • Zahra Tayarani-NajaranEmail author
Original Article


Alzheimer’s disease is a type of cerebrovascular problem with progressive mental disabilities for the patient. This study aimed to investigate the protective effect of safranal on toxicity and oxidative damage induced by beta-amyloid (Aβ) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer’s cell damage. PC12 cells pretreated with saffron extract (2.5–40 μg/ml), essential oil (2.5–40 μg/ml), safranal (2.5–5-40 μM) and donepezil (5, 10 and 20 μM) for 120 min. Then exposed to either Aβ (25 μM) for 48 h or H2O2 (150 μM) for 24 h. In the end, the cell survival and intracellular reactive oxygen species (ROS) production analyzed. The anti-apoptotic effects of safranal in PC12 cells were studied using flow cytometry after PI staining. Also, western blot analysis of Cyt c, survivin, p44/42 MAPK (ERK1/2), Phospho-p44/42 MAPK (ERK1/2), PI3 Kinase P85, Phospho-PI3 Kinase P85, phospho SAPK/JNK, SAPK/JNK and caspase 3 performed for detection of apoptosis. Safranal (2.5 and 5 μM) and donepezil (10 and 20 μM) significantly decreased the Aβ toxicity. The ROS significantly attenuated when cells pretreated with essential oil, saffron extract, safranal, and donepezil. Cell apoptosis significantly increased after treatment with Aβ (25–35) (25 μM) compared to control. However, after pretreatment with safranal (2.5 μM) apoptosis was significantly reduced. Western blot analysis of PC12 cells showed that 25 μM Aβ (25–35) could increase proteins involved in apoptosis signaling and pretreatment with safranal (2.5 μM) could decrease the apoptosis. According to the results, safranal showed anti-apoptotic and antioxidant effects and may exert promising potential for the prevention of Alzheimer’s disease.


Alzheimer’s disease Beta-amyloid Apoptosis Crocus sativus, Safranal, saffron 



The authors thank Mr. Malaeke for reading the flowcytometry samples. We are also thankful to Dr. H. Hosseinzadeh and Dr. F. Hadizadeh for donating safranal and crocin, respectively.


This work has been performed at Pharmacy School and is supported by grant No. 931772 from the Research Affairs of Mashhad University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Faezeh Rafieipour
    • 1
  • Elham Hadipour
    • 2
  • Seyed Ahmad Emami
    • 3
  • Javad Asili
    • 3
  • Zahra Tayarani-Najaran
    • 4
    Email author
  1. 1.Department of Traditional Pharmacy, School of PharmacyMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Biology, Faculty of ScienceFerdowsi University of MashhadMashhadIran
  3. 3.Department of Pharmacognosy, School of PharmacyMashhad University of Medical SciencesMashhadIran
  4. 4.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran

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