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Safranal protects against ischemia-induced PC12 cell injury through inhibiting oxidative stress and apoptosis

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Abstract

Safranal, isolated from saffron (Crocus sativus L.), is known to possesses neuroprotective effects. In this study, the neuroprotective potential of safranal against PC12 cell injury triggered by ischemia/reperfusion was investigated. PC12 cells were pretreated with safranal at concentration ranges of 10–160 μM for 2 h and then deprived from oxygen-glucose-serum for 6 h, followed by reoxygenation for 24 h (OGD condition). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2,7-dichlorofluorescin diacetate (DCF-DA), and comet assays were used to measure the extent of cellular viability, reactive oxygen substances (ROS), and DNA damage, respectively. Also, propidium iodide (PI) flow cytometry assay and western blotting of bax, bcl-2, and cleaved caspase-3 were performed for assessment of apoptosis. OGD exposure reduced the cell viability and increased intracellular ROS production, oxidative DNA damage, and apoptosis, in comparison with untreated control cells. Pretreatment with safranal (40 and 160 μM) significantly attenuated OGD-induced PC12 cell death, oxidative damage, and apoptosis. Furthermore, safranal markedly reduced the overexpression of bax/bcl-2 ratio and active caspase-3 following OGD (p < 0.05). The present findings indicated that safranal protects against OGD-induced neurotoxicity via modulating of oxidative and apoptotic responses.

Graphical abstract

The schematic representation of the mode of action of safranal against PC12 cells death induced by oxygen-glucose-serum deprivation and reoxygenation (OGD-R).

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Funding

The authors received financial support from Vice Chancellery for Research and Technology, Mashhad University of Medical Sciences (grant numbers: 89502, 900950).

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Authors and Affiliations

  1. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar

  2. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Forouzanfar

  3. Anaestehsiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Elham Asadpour

  4. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Hosseinzadeh

  5. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, PO Box 99199-91766, Mashhad, Iran

    Mohammad Taher Boroushaki & Hamid R. Sadeghnia

  6. Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, PO Box 99199-91766, Mashhad, Iran

    Afrouz Adab & Hamid R. Sadeghnia

  7. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, PO Box 99199-91766, Mashhad, Iran

    Seyedeh Hoda Dastpeiman & Hamid R. Sadeghnia

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  1. Fatemeh Forouzanfar
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  2. Elham Asadpour
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  3. Hossein Hosseinzadeh
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  4. Mohammad Taher Boroushaki
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  5. Afrouz Adab
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  6. Seyedeh Hoda Dastpeiman
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  7. Hamid R. Sadeghnia
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Contributions

Elham Assadpour and Fatemeh Forouzanfar wrote the first draft of the article. Mohammad Taher Boroushaki and Hossein Hosseinzadeh were advisors. Elham Asadpour, Afrouz Adab, Seyedeh Hoda Dastpeiman, and Fatemeh Forouzanfar performed the experiments. Hamid Reza Sadeghnia supervised the whole project and prepared the final draft of the paper. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Hamid R. Sadeghnia.

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Forouzanfar, F., Asadpour, E., Hosseinzadeh, H. et al. Safranal protects against ischemia-induced PC12 cell injury through inhibiting oxidative stress and apoptosis. Naunyn-Schmiedeberg's Arch Pharmacol 394, 707–716 (2021). https://doi.org/10.1007/s00210-020-01999-8

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