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Thymoquinone Prevents β-Amyloid Neurotoxicity in Primary Cultured Cerebellar Granule Neurons

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Abstract

Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1–40 sequence (Aβ1–40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1–40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1–40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1–40 alone. TQ pretreatment inhibited Aβ1–40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1–40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer’s disease.

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Abbreviations

Aβ:

Beta-amyloid peptide

AD:

Alzheimer’s disease

TQ:

Thymoquinone

CGNs:

Primary cultured cerebellar granule neurons

PC12:

Pheochromocytoma

MTS:

3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

LDH:

Lactate dehydrogenase

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate buffered saline

DMPO:

5,5-Dimethyl-1-pyrroline-1-oxide

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Acknowledgments

Authors are thankful to Government of Malaysia and Universiti Putra Malaysia for providing financial support for this work via Research University Grant.

Conflict of interests

None of the authors have any conflict of interest.

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Authors and Affiliations

  1. Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Norsharina Ismail, Maznah Ismail, Mustapha Umar Imam, Shahid Iqbal, Nur Hanisah Azmi, Siti Aisyah Abd Ghafar & Kim Wei Chan

  2. Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Maznah Ismail

  3. Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi Mara, Campus Sungai Buloh, Jalan Hospital, 47000, Sungai Buloh, Selangor, Malaysia

    Musalmah Mazlan

  4. Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Latiffah Abdul Latiff

  5. Cancer Resource and Education Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia

    Latiffah Abdul Latiff

  6. Department of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan

    Shahid Iqbal

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  1. Norsharina Ismail
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Correspondence to Maznah Ismail.

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Ismail, N., Ismail, M., Mazlan, M. et al. Thymoquinone Prevents β-Amyloid Neurotoxicity in Primary Cultured Cerebellar Granule Neurons. Cell Mol Neurobiol 33, 1159–1169 (2013). https://doi.org/10.1007/s10571-013-9982-z

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  • DOI: https://doi.org/10.1007/s10571-013-9982-z

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