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

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Abstract

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.

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Acknowledgments

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.

Funding

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.

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Authors and Affiliations

  1. Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Faezeh Rafieipour

  2. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Elham Hadipour

  3. Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Ahmad Emami & Javad Asili

  4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, P.O. Box: 9188617871, Mashhad, Iran

    Zahra Tayarani-Najaran

Authors
  1. Faezeh Rafieipour
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  2. Elham Hadipour
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  5. Zahra Tayarani-Najaran
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Correspondence to Zahra Tayarani-Najaran.

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Rafieipour, F., Hadipour, E., Emami, S. et al. Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways. Metab Brain Dis 34, 165–172 (2019). https://doi.org/10.1007/s11011-018-0329-9

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  • DOI: https://doi.org/10.1007/s11011-018-0329-9

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