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Volume 31, Issue 9
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Aim

This study aimed to investigate how diosmetin interacts with seven target receptors associated with oxidative stress (OS) and validate its antioxidant properties for the potential management of Parkinson’s disease (PD).

Background

In PD, the degeneration of dopaminergic cells is strongly influenced by OS. This stressor is intricately connected to various mechanisms involved in neurodegeneration, such as mitochondrial dysfunction, neuroinflammation, and excitotoxicity induced by nitric oxide.

Objective

The aim of this research was to establish a molecular connection between diosmetin and OS-associated target receptors was the goal, and it investigated how this interaction can lessen PD.

Methods

Seven molecular targets - Adenosine A2A (AA2A), Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Protein Kinase AKT1, Nucleolar Receptor NURR1, Liver - X Receptor Beta (LXRβ), Monoamine Oxidase - B (MAO-B) and Tropomyosin receptor kinase B (TrkB) were obtained from RCSB. Molecular docking software was employed to determine molecular interactions, while antioxidant activity was assessed through assays against various free radicals.

Results

Diosmetin exhibited interactions with all seven target receptors at their binding sites. Notably, it showed superior interaction with AA2A and NURR1 compared to native ligands, with binding energies of -7.55, and -6.34 kcal/mol, respectively. Additionally, significant interactions were observed with PPARγ, AKT1, LXRβ, MAO-B, and TrkB with binding energies of -8.34, -5.42, -7.66, -8.82, -8.45 kcal/mol, respectively. Diosmetin also demonstrated antioxidant activity against various free radicals, particularly against hypochlorous acid (HOCl) and nitric oxide (NO) free radicals.

Conclusion

Diosmetin possibly acts on several target receptors linked to the pathophysiology of PD, demonstrating promise as an OS inhibitor and scavenger.

© 2024 Bentham Science Publishers
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2024-12-23

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/content/journals/ppl/10.2174/0109298665333333240909104354
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Investigating In silico and In vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent
PPL 31, 714 (2024); https://doi.org/10.2174/0109298665333333240909104354
/content/journals/ppl/10.2174/0109298665333333240909104354
/content/journals/ppl/10.2174/0109298665333333240909104354
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  • Article Type:     Research Article
Keyword(s): antioxidant; Diosmetin; free radicals; molecular interactions; oxidative stress; Parkinson’s disease

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