Molecular and Cellular Biochemistry

, Volume 369, Issue 1, pp 55–65

Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress

  • Andleeb Khan
  • Kumar Vaibhav
  • Hayate Javed
  • Mohd. Moshahid Khan
  • Rizwana Tabassum
  • Md. Ejaz Ahmed
  • Pallavi Srivastava
  • Gulrana Khuwaja
  • Farah Islam
  • Mohd. Saeed Siddiqui
  • Mohammed M. Shafi
  • Fakhrul Islam
Article

DOI: 10.1007/s11010-012-1368-x

Cite this article as:
Khan, A., Vaibhav, K., Javed, H. et al. Mol Cell Biochem (2012) 369: 55. doi:10.1007/s11010-012-1368-x

Abstract

Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer’s disease (AD) and compounds that can prevent pathways of Aβ-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) would reduce oxidative stress and mitochondrial dysfunction in differentiated pheochromocytoma (PC 12) cells exposed to Aβ fragment 25–35 (Aβ25–35). To test this hypothesis, Aβ was used to induce an in vitro model of AD in differentiated PC 12 cell line of rat. After 24 h of exposure with Aβ25–35, a significant reduction in cell viability and mitochondrial membrane potential (MMP) was observed. In addition, a significant elevation in the TBARS content and nitric oxide (NO) and activity of acetylcholine esterase (AChE) was observed which was restored significantly by TQ pretreatment. Furthermore, TQ also ameliorated glutathione and its dependent enzymes (glutathione peroxidase, glutathione reductase) which were depleted by Aβ25–35 in PC 12 cells. These results were supported by the immunocytochemical finding that has shown protection of cells by TQ from noxious effects of Aβ25–35. These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders including AD.

Keywords

Alzheimer’s disease PC 12 cells 25–35 Oxidative stress Thymoquinone 

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Andleeb Khan
    • 1
  • Kumar Vaibhav
    • 1
  • Hayate Javed
    • 1
  • Mohd. Moshahid Khan
    • 1
    • 4
  • Rizwana Tabassum
    • 1
  • Md. Ejaz Ahmed
    • 1
  • Pallavi Srivastava
    • 1
    • 5
  • Gulrana Khuwaja
    • 1
    • 3
  • Farah Islam
    • 2
  • Mohd. Saeed Siddiqui
    • 1
  • Mohammed M. Shafi
    • 3
  • Fakhrul Islam
    • 1
    • 3
    • 6
  1. 1.Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology (Fund for the Improvement of Science and Technology Sponsored by DST and Special Assistance Programme Sponsored by UGC)Jamia Hamdard (Hamdard University)New DelhiIndia
  2. 2.Department of Biotechnology, Faculty of PharmacyJamia Hamdard (Hamdard University)New DelhiIndia
  3. 3.Neuroscience and Toxicology Unit, Faculty of PharmacyJazan UniversityJazanKingdom of Saudi Arabia
  4. 4.Department of Neurology, Carver College of MedicineUniversity of IowaIowa CityUSA
  5. 5.Department of NeurologyUMDNJ, Robert Wood Johanson Medical SchoolBrunswickUSA
  6. 6.Department of Pharmaceutical Chemistry, Faculty of PharmacyJazan UniversityJazanSaudi Arabia