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CC BY 4.0 · Indian Journal of Neurotrauma
DOI: 10.1055/s-0044-1795153
Original Article

Neuroprotective Role of Ranolazine: ESR1 and NMDA Receptor Agonist in Traumatic Brain Injury in Drosophila melanogaster, In Silico and In Vivo Correlation

Parvesh Parvesh
1   Department of Pharmacology, Sarvhind College of Pharmacy, Rewari, Haryana, India
,
Sandeep Kumar
2   Department of Pharmaceutical Sciences, MM College of Pharmacy, Maharishi Markandeshwar Campus, Mullana, Ambala, Haryana, India
,
Govind Singh
3   Department of Pharmaceutical Sciences, Maharishi Dayanand University, Rohtak, India
,
Ramchander Khatri
4   Delhi Pharmaceutical Sciences and Research University, New Delhi, Delhi, India
,
Sarita Sharma
5   Department of Pharmacology, Geeta Institute of Pharmacy, Geeta University, Panipat, India
,
Amit Lather 
2   Department of Pharmaceutical Sciences, MM College of Pharmacy, Maharishi Markandeshwar Campus, Mullana, Ambala, Haryana, India
,
Tanuj Hooda 
2   Department of Pharmaceutical Sciences, MM College of Pharmacy, Maharishi Markandeshwar Campus, Mullana, Ambala, Haryana, India
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Abstract

Objective In this study, a high-impact trauma (HIT) device was used for inducing moderate traumatic brain injury (TBI) in Drosophila melanogaster. Mechanical injuries in flies caused by rapid acceleration and assertion produce symptoms characteristics of TBI in humans.

Materials and Methods Docking studies were carried out to check the binding affinity of the drug toward the receptors. Various oxidative stress parameters, catalase level, glutathione level, superoxide dismutase (SOD) level, malondialdehyde (MDA), and nitric oxide levels, were measured. The mortality index and neuroprotective potential were carried out in TBI in D. melanogaster models.

Results In the current study, there was an increase in oxidative stress following TBI as evidenced by a significant decrease in the catalase, glutathione, and SOD levels and increase in the level of MDA and nitric oxide after 24 hours. Antioxidant enzymes, catalase and glutathione peroxidase, have a dominant role in TBI. Docking studies were carried out on estrogen receptor 1 (pdb: 1TVO and 1UOM) and NDMA receptor (pdb: 3QEL) as agonist showing the binding affinity of the drug toward the receptors. In comparison to the vehicle-treated group, there was a dose-dependent significant increase in the SOD level and percentage climbing along with a decrease in the MDA level and total protein content. The mortality index was also observed at three concentrations of ranolazine (1, 2, and 4 mg/mL) in D. melanogaster homogenate. These findings suggest that ranolazine has a good neuroprotective potential in the treatment of TBI in the D. melanogaster model.

Conclusion Present study concluded the scientific evaluation of neuroprotective potential of ranolazine in the treatment of TBI in the D. melanogaster model.

Keywords

traumatic - ranolazine - Drosophila melanogaster - docking - TBI


Publication History

Article published online:
25 November 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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