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Ameliorative effect of ethoxylated chalcone-based MAO-B inhibitor on behavioural predictors of haloperidol-induced Parkinsonism in mice: evidence of its antioxidative role against Parkinson’s diseases

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Abstract

Parkinson’s disease is a progressive neurodegenerative disorder that affects mostly elderly people above the age of 60. Previously, we have reported that the ethoxylated chalcone derivative (E)-1-(4-ethoxyphenyl)-3-(fluorophenyl)prop-2-en-1-one (E7) showed potent, reversible, and competitive MAO-B inhibition with an IC50 value of 0.053 μm. The present study aims to investigate the anti-Parkinson activity of compound E7 in a haloperidol-induced animal model of mice. The disease was induced with haloperidol (1 mg/kg, intraperitoneal route) once daily for 21 days. E7 was given at dose levels of 10, 20, and 30 mg/kg/day for 21 days, consecutively. Behavioural tests were carried out during and at the end of the study. Biochemical analyses such as oxidative stress biomarkers and neurotransmitters were quantified on the brain homogenate at the end of the study. Behavioural results showed that there is a marked improvement in locomotor activity and motor coordination in the treatment group. Oxidative stress biomarkers such as SOD, CAT, and GSH levels were increased dose-dependently with a maximum at 30 mg/kg, whereas the dose-dependent decrease (30 mg/kg) in the MDA and nitrite levels were observed in the treatment groups. Levels of neurotransmitters, such as dopamine, serotonin, and noradrenaline, were increased in the treatment groups while dopamine and noradrenaline levels were more than in the standard treated group. MAO-B level was also decreased dose dependently in the treatment group in comparison with the control group. Based on the findings, it was concluded that the E7 compound exhibited anti-Parkinson activity which was more evident at 30 mg/kg oral dose as evaluated by the haloperidol-induced animal model of mice.

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Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research (DSR) at King Khalid University (KKU), Abha, Saudi Arabia, for funding this work through the Research Group Project under the grant number: R.G.P/159/42.

Funding

Deanship of Scientific Research (DSR) at King Khalid University (KKU), Abha, Saudi Arabia, for funding this work through the Research Group Project under the grant number: R.G.P/159/42.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, College of Applied Medical Sciences in Khamis Mushayt, King Khalid University, Abha, Saudi Arabia

    Naseer Maliyakkal & Mohammad Ali Abdullah Almoyad

  2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan

    Uzma Saleem

  3. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, 54000, Pakistan

    Fareeha Anwar, Bashir Ahmad & Filzah Umer

  4. Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan

    Muhammad Ajmal Shah

  5. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Al Jouf-2014, Sakaka, Saudi Arabia

    Della Grace Thomas Parambi

  6. Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

    Asmy Appadath Beeran

  7. Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India

    Lekshmi R Nath

  8. Laboratoire Chrono-Environnement, CNRS6249, Universite de Bourgogne Franche-Comte, Besancon, France

    Lotfi Aleya

  9. Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India

    Bijo Mathew

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  1. Naseer Maliyakkal
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  12. Bijo Mathew
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Contributions

B. Mathew synthesized the molecule, planned the study, and edited the manuscript. N. Maliyakkal, U. Saleem, F. Anwar, M. A. Shah, B. Ahmad, F. Umer, M. A. A. Almoyad, D. G. T. Parambi, and A. A. Beeran have performed the biological evaluation. Data curation and writing the original draft preparation done by B. Mathew, L.R. Nath, and L. Aleya.

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Correspondence to Naseer Maliyakkal, Uzma Saleem or Bijo Mathew.

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Maliyakkal, N., Saleem, U., Anwar, F. et al. Ameliorative effect of ethoxylated chalcone-based MAO-B inhibitor on behavioural predictors of haloperidol-induced Parkinsonism in mice: evidence of its antioxidative role against Parkinson’s diseases. Environ Sci Pollut Res 29, 7271–7282 (2022). https://doi.org/10.1007/s11356-021-15955-3

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