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Quercetin’s Restorative Properties in Male Mice with 3-Nitropropionic Acid-induced Huntington-like Symptoms: Molecular Docking, Behavioral, and Biochemical Assessment

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Abstract

The neurotoxicity of 3-Nitropropionic acid (3-NP) is well known. Herein, the prophylactic versus therapeutic effects of quercetin (QCT) were investigated against 3-NP-induced behavioral anomalies and oxidative neural damage. Thirty male mice were assigned into five groups; the negative control group, the QCT group (25 mg/kg/day, p.o. for 21 days), the 3-NP group (17 days), the prophylactic group (QCT administration for 14 consecutive days, and then 3-NP was administrated), the therapeutic group (3-NP was administrated and then QCT for 21 days). At the end of the animal treatment, behavioral studies were assessed. Subsequently, the brain sample tissues were assessed for oxidative stress-related parameters and histological evaluation. Moreover, the potential interaction between 3-NP and tumor necrosis factor-alpha (TNF-α) was evaluated by using a molecular docking study. 3-NP markedly led to neurotoxicity which was indicated by behavioral deficits (motor behavior, depression-like behavior, memory dysfunction, and passive avoidance) and oxidative damage. Blind and targeted molecular docking results showed good interaction between 3-NP and TNF-α. However, the prophylactic effects of QCT were superior to the therapeutic effects for attenuating 3-NP-induced neurobehavioral and oxidative neural changes in experimental mice, which histological changes of the brain’s striatum region approved our findings. Taken together, the antioxidant activity of QCT remarkably could attenuate 3-NP-induced neurobehavioral deficits and mitochondrial dysfunctions in mice.

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Acknowledgements

We would like to thank Hamadan University of Medical Sciences for supporting this study.

Funding

This work was supported by a grant from the Research and Technology Vice-Chancellor of Hamadan University of Medical Sciences, Hamadan, Iran (Grant No: 9804253251).

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  1. These authors contributed equally: Sajjad Makhdoomi, Ahmad Fadaiie.

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  1. Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

    Sajjad Makhdoomi, Ahmad Fadaiie, Mojdeh Mohammadi, Akram Ranjbar & Rasool Haddadi

  2. Medicinal Plant and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Rasool Haddadi

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S.M. implemented the molecular docking, and statistical analysis, and wrote the main manuscript. A.F. collected and analyzed data. A.R. was the advisor and was involved in manuscript editing. M.M. and R.H. were the study’s supervisors and were involved in conceptualization and manuscript editing. All authors reviewed the manuscript.

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Makhdoomi, S., Fadaiie, A., Mohammadi, M. et al. Quercetin’s Restorative Properties in Male Mice with 3-Nitropropionic Acid-induced Huntington-like Symptoms: Molecular Docking, Behavioral, and Biochemical Assessment. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01302-z

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