Investigating In silico and In vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent.

IF 1.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Protein and Peptide Letters Pub Date : 2024-01-01 DOI:10.2174/0109298665333333240909104354

Krishna Kumar Varshney, Jeetendra Kumar Gupta, Rajnish Srivastava

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引用次数: 0

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 in vitro 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.

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研究 Diosmetin 作为抗帕金森药物的体内和体外治疗潜力。

目的：本研究旨在调查香叶木素如何与七个与氧化应激（OS）相关的靶受体相互作用，并验证其抗氧化特性对帕金森病（PD）的潜在治疗作用：背景：在帕金森病中，多巴胺能细胞的退化受到氧化应激的强烈影响。背景：在帕金森病中，多巴胺能细胞的退化受到操作系统的强烈影响。这种应激源与神经退行性病变的各种机制密切相关，如线粒体功能障碍、神经炎症和一氧化氮诱导的兴奋毒性：本研究的目的是建立地奥司明与OS相关靶受体之间的分子联系，并探讨这种相互作用如何减轻PD：从RCSB获得七个分子靶点--腺苷A2A（AA2A）、过氧化物酶体激活受体γ（PPARγ）、蛋白激酶AKT1、核极受体NURR1、肝X受体β（LXRβ）、单胺氧化酶B（MAO-B）和肌球蛋白受体激酶B（TrkB）。采用分子对接软件确定分子相互作用，同时通过体外试验评估其对各种自由基的抗氧化活性：结果：Diosmetin 与所有七个目标受体的结合位点都有相互作用。值得注意的是，与原生配体相比，它与 AA2A 和 NURR1 的相互作用更强，结合能分别为 -7.55 和 -6.34 kcal/mol。此外，与 PPARγ、AKT1、LXRβ、MAO-B 和 TrkB 也有明显的相互作用，结合能分别为 -8.34、-5.42、-7.66、-8.82 和 -8.45kcal/mol。香叶木素还具有抗氧化活性，可对抗各种自由基，尤其是次氯酸（HOCl）和一氧化氮（NO）自由基：结论：香叶木素可能作用于与帕金森病病理生理学有关的多个靶受体，有望成为操作系统抑制剂和清除剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis