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Reversal of oxidative stress, cytokine toxicity and DNA fragmentation by quercetin in dizocilpine-induced animal model of Schizophrenia

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Abstract

Quercetin, a polyphenolic compound found in a variety of plant products possesses various biological activities and beneficial effects on human health. Schizophrenia (SZ) is one of the neuropsychiatric disorders in human beings with rapid mortality and intense morbidity which can be treated with antipsychotics, but these commercial drugs exert adverse effects and have less efficacy to treat the full spectrum of SZ. The present study was conducted to evaluate neuroprotective effects of quercetin in the preventive and therapeutic treatment of SZ. Quercetin was administered as pre- and post-regimens at the dose of 50 mg/kg in dizocilpine-induced SZ rat model for two weeks. Rats were then subjected for the assessment of different behaviors followed by biochemical, neurochemical, and inflammatory marker analyses. The present findings revealed that quercetin significantly reverses the effects of dizocilpine-induced psychosis-like symptoms in all behavioral assessments as well as it also combats oxidative stress. This flavonoid also regulates dopaminergic, serotonergic, and glutamatergic neurotransmission. A profound effect on inflammatory cytokines and decreased %DNA fragmentation was also observed following the administration of quercetin. The findings suggest that quercetin can be considered as a preventive as well as therapeutic strategy to attenuate oxidative stress and cytokine toxicity, regulate neurotransmission, and prevent enhanced DNA fragmentation that can lead to the amelioration of psychosis-like symptoms in SZ.

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Acknowledgements

The authors are thankful to the University of Karachi for providing the research facility.

Funding

Haider S received financial support from Higher Education Commission, Pakistan (http://www.hec.gov.pk/english/pages/home.aspx), under the approved project NRPU-4480. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan

    Sidrah Shahzad, Asia Afzal & Saida Haider

  2. Pakistan Navy Medical Training School and College, PNS Shifa, Karachi, Pakistan

    Sidrah Shahzad

  3. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Zehra Batool

  4. Collaborative Drug Discovery Research (CDDR) Group and Brain Degeneration and Therapeutics Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Cawangan Selangor, Kampus Puncak Alam, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia

    Asia Afzal

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sidrah Shahzad, Zehra Batool and Asia Afzal. Saida Haider supervised the research project. The first draft of the manuscript was written by Sidrah Shahzad, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zehra Batool.

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The experimental work performed in this study was approved by the Advanced Studies and Research Board of Institute (ASRB/02926/Sc.).

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Shahzad, S., Batool, Z., Afzal, A. et al. Reversal of oxidative stress, cytokine toxicity and DNA fragmentation by quercetin in dizocilpine-induced animal model of Schizophrenia. Metab Brain Dis 37, 2793–2805 (2022). https://doi.org/10.1007/s11011-022-01090-6

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