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高分辨率常压基质辅助激光解吸/电离质谱蛋白质组学对[具体物质]抗丝虫作用的见解:对基于植物化学物质的药物靶向和设计的启示

HRAMS Proteomics Insights on the Anti-Filarial Effect of : Implications in Phytochemical-Based Drug-Targeting and Designing.

作者信息

Mishra Ayushi, Kumar Vipin, Kumar Sunil, Singh HariOm, Singh Anchal

机构信息

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Department of Molecular Biology, National Aids Research Institute, Pune 411026, India.

出版信息

Proteomes. 2024 Dec 27;13(1):2. doi: 10.3390/proteomes13010002.

Abstract

Lymphatic filariasis (LF) continues to impact 657 million individuals worldwide, resulting in lifelong and chronic impairment. The prevalent anti-filarial medications-DEC, albendazole, and ivermectin-exhibit limited adulticidal efficacy. Despite ongoing LF eradication programs, novel therapeutic strategies are essential for effective control. This study examines the mechanism of action of on the filarial parasites via a synergistic biochemical and proteomics methodology. The ethanolic extract of (EOS) demonstrated potential anti-filarial action in the MTT reduction experiment, with an LC value of 197.24 µg/mL. After EOS treatment, an elevation in lipid peroxidation (51.92%), protein carbonylation (48.99%), and NADPH oxidase (88.88%) activity, along with a reduction in glutathione (GSH) (-39.23%), glutathione reductase (GR) (-60.17%), and glutathione S transferase (GST) (-50.48%) activity, was observed. The 2D gel electrophoresis identified 20 decreased and 11 increased protein spots in the EOS-treated parasites relative to the control group. Additionally, in drug docking analysis, the EOS bioactive substances ursolic acid, rutin, and rosmarinic acid show a significant binding affinity with the principal differentially expressed proteins. This paper demonstrates, for the first time, that the anti-filarial efficacy of EOS is primarily facilitated by its impact on energy metabolism, antioxidant mechanisms, and stress response systems of the parasites.

摘要

淋巴丝虫病(LF)继续影响着全球6.57亿人,导致终身慢性损伤。目前常用的抗丝虫药物——乙胺嗪、阿苯达唑和伊维菌素——对成虫的杀灭效果有限。尽管正在开展淋巴丝虫病消除计划,但新的治疗策略对于有效控制该病至关重要。本研究通过协同生化和蛋白质组学方法研究了[具体物质]对丝虫寄生虫的作用机制。[具体植物]的乙醇提取物(EOS)在MTT还原实验中显示出潜在的抗丝虫作用,LC值为197.24µg/mL。EOS处理后,观察到脂质过氧化(51.92%)、蛋白质羰基化(48.99%)和NADPH氧化酶(88.88%)活性升高,同时谷胱甘肽(GSH)(-39.23%)、谷胱甘肽还原酶(GR)(-60.17%)和谷胱甘肽S转移酶(GST)(-50.48%)活性降低。二维凝胶电泳鉴定出与对照组相比,EOS处理的寄生虫中有20个蛋白质斑点减少,11个蛋白质斑点增加。此外,在药物对接分析中,EOS的生物活性物质熊果酸、芦丁和迷迭香酸与主要差异表达蛋白显示出显著的结合亲和力。本文首次证明,EOS的抗丝虫功效主要是通过其对寄生虫能量代谢、抗氧化机制和应激反应系统的影响来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bf/11755628/d98934dd84bf/proteomes-13-00002-g001.jpg

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