Xanthine oxidase inhibitory kinetics and mechanism of ellagic acid: In vitro, in silico and in vivo studies

IF 3.8 4区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS IET nanobiotechnology Pub Date : 2023-05-08 DOI:10.1049/nbt2.12135

Jianmin Chen, Zemin He, Sijin Yu, Xiaozhen Cai, Danhong Zhu, Yanhua Lin

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Abstract

Ellagic acid (EA), which is widely distributed in many foods, has been found to possess inhibitory activity against xanthine oxidase (XO). However, there is ongoing debate about the difference in XO inhibitory activity between EA and allopurinol. Additionally, the inhibitory kinetics and mechanism of EA on XO are still unclear. Herein, the authors systematically studied the inhibitory effects of EA on XO. The authors’ findings showed that EA is a reversible inhibitor with mixed-type inhibition, and its inhibitory activity is weaker than allopurinol. Fluorescence quenching experiments suggested that the generation of EA-XO complex was exothermic and spontaneous. In silico analysis further confirmed that EA entered the XO catalytic centre. Furthermore, the authors verified the anti-hyperuricemia effect of EA in vivo. This study elucidates the inhibition kinetics and mechanism of EA on XO, and lays a theoretical foundation for the further development of drugs and functional foods containing EA for the treatment of hyperuricemia.

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鞣花酸黄嘌呤氧化酶抑制动力学和机制:体外、硅和体内研究

鞣花酸(eragic acid, EA)广泛存在于多种食品中，具有抑制黄嘌呤氧化酶(xanthine oxidase, XO)的活性。然而，关于EA和别嘌呤醇之间XO抑制活性的差异仍存在争议。此外，EA对XO的抑制动力学和机制尚不清楚。本文系统地研究了EA对XO的抑制作用。结果表明，EA是一种可逆的混合型抑制抑制剂，其抑制活性弱于别嘌呤醇。荧光猝灭实验表明，EA-XO配合物的生成是放热自发的。硅分析进一步证实EA进入了XO催化中心。此外，作者还在体内验证了EA抗高尿酸血症的作用。本研究阐明了EA对XO的抑制动力学和机制，为进一步开发含EA治疗高尿酸血症的药物和功能食品奠定了理论基础。

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来源期刊

IET nanobiotechnology 工程技术-纳米科技

CiteScore

6.20

自引率

4.30%

发文量

审稿时长

1 months

期刊介绍： Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf