Rosolic acid as a novel activator of the Nrf2/ARE pathway in arsenic-induced male reproductive toxicity: An in silico study.
| Autor: | Mukherjee AG; Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India., Valsala Gopalakrishnan A; Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India. |
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| Jazyk: | angličtina |
| Zdroj: | Biochemistry and biophysics reports [Biochem Biophys Rep] 2024 Jul 29; Vol. 39, pp. 101801. Date of Electronic Publication: 2024 Jul 29 (Print Publication: 2024). |
| DOI: | 10.1016/j.bbrep.2024.101801 |
| Abstrakt: | Male reproductive toxicity as a result of arsenic exposure is linked with oxidative stress and excessive generation of reactive oxygen species (ROS). It leads to an imbalance between ROS production and antioxidant defense mechanisms ultimately resulting in male infertility. The nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor that responds to cellular stressors controlling the oxidative state, mitochondrial dysfunction, inflammation, and proteostasis. This study aims to investigate the potential of Rosolic acid (ROA) to act as a novel Nrf2 activator by mitigating oxidative stress to combat arsenic-induced male reproductive toxicity. The protein and ligands were prepared in the BIOVIA Discovery Studio, followed by protein-ligand docking using auto dock vina integrated with the PyRx-Virtual Screening Tool. Then the ADME properties were analyzed using the SwissADME tool to get a clear idea about the physicochemical properties, lipophilicity, water solubility, pharmacokinetics, and drug likeliness of ROA. It was followed by molecular dynamics simulation (MDS) studies using GROMACS. The 3D and 2D interaction maps revealed the interactions of Keap 1 with ROA. Keap1-ROA complex was found to have a binding energy of -7.8 kcal/mol. ROA showed 0 violations for Lipinski and 0 alerts each for PAINS and Brenk and a bioavailability score of 0.55. The BOILED-Egg representation showcases that ROA is predicted as passively crossing the blood-brain barrier (BBB). The MDS described 2FLU-ROA as a stable system. This work portrays that ROA can be a potent Nrf2 activator by exhibiting an inhibitory activity against the Keap1 protein and thus mitigating oxidative stress in arsenic-induced male reproductive toxicity. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.) |
| Databáze: | MEDLINE |
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