Exploring the Mechanism of 2'-Hydroxychalcone Improving Copper Sulfate-Induced Inflammation in Zebrafish Through Network Pharmacology.

IF 5.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Drug Design, Development and Therapy Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S510195
YuZhou Shen, Yan Dong Yao, Haili Li, Qian Zhang, Cheng Lin Wang, Li Hu, Ying Chun Hu, Mu Hu Chen
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引用次数: 0

Abstract

Introduction: 2'-Hydroxychalcone is universally acknowledged as a Chinese medicine monomer featured by aromatic properties, exhibiting anti-inflammatory and antioxidant effects. As a consequence, the study emphasis was placed on the anti-inflammatory, anti-oxidative and exercise capacity reinforcement effects of 2'-Hydroxychalcone on Danio rerio young fish under the action of CuSO4. Simultaneously, research endeavors were made to delve into how functional changes of target affect the inflammation and exercise capacity of Danio rerio young fish.

Methods: Upon mating breeding, mature transgenic zebrafish and type AB zebrafish expressing red fluorescent macrophages T g (mpeg1:m Cherry) were cultured for 72 h and exposed to 12.5, 6.25, 3.14 and 0uM 2'-Hydroxychalcone, respectively, for three hours of pretreatment, which were subsequently incubated in CuSO4 at 20uM concentration for 12 h. A diverse array of test indexes was hereby utilized, encompassing the migration of red fluorescent-labeled macrophages, levels of inflammatory cytokines, zebrafish behavioral motility, and gene expression patterns correlated with oxidative stress and mitochondrial biogenesis, to assess the drugs' efficacy in alleviating inflammation.

Results: 2'-Hydroxychalcone anti-inflammatory target protein was found by adopting the bioinformatics method. Its effect on zebrafish behavior ability and the change trend of oxidative stress index were explored by changing the functional state of the target, such as changing the functional activity of the target by micro-injection technology. As indicated by the results, 2'-Hydroxychalcone could hinder the migration of macrophages and the mitochondrial function of CuSO4. Apart from that, 2'-Hydroxychalcone could lessen the level of inflammatory factors and oxidative stress. In addition, 2'-Hydroxychalcone conspicuously hindered the expression of interleukin-1β and interleukin-TNF-α, and lowered the expression of COX2. An augment in the levels of the target protein TRPV1 was observed during inflammation.

Discussion: The experimental findings validated the anti-inflammatory and anti-oxidant activities of 2'-Hydroxychalcone and preliminarily confirmed the effect of the target on the behavior and oxidative stress level of zebrafish.

网络药理学探讨2′-羟基查尔酮改善硫酸铜诱导斑马鱼炎症的机制。
2′-羟基查尔酮是公认的具有芳香特性的中药单体,具有抗炎和抗氧化作用。因此,本研究重点研究了2′-羟查尔酮在CuSO4作用下对达尼欧幼鱼的抗炎、抗氧化和增强运动能力的作用。同时,研究靶点的功能改变如何影响达尼欧鱼幼鱼的炎症和运动能力。方法:交配繁殖后,将成熟的转基因斑马鱼和表达红色荧光巨噬细胞T g (mpeg1:m Cherry)的AB型斑马鱼分别培养72 h,分别暴露于12.5、6.25、3.14和0 μ m的2′-羟查尔酮中预处理3小时,随后在浓度为20 μ m的CuSO4中孵育12 h。我们采用了多种测试指标,包括红色荧光标记巨噬细胞的迁移、炎症因子水平、斑马鱼的行为运动,以及与氧化应激和线粒体生物发生相关的基因表达模式,以评估药物减轻炎症的功效。结果:采用生物信息学方法发现2′-羟基查尔酮抗炎靶蛋白。通过改变靶点的功能状态,如通过微注射技术改变靶点的功能活性,探索其对斑马鱼行为能力的影响以及氧化应激指数的变化趋势。结果表明,2′-羟基查尔酮可抑制巨噬细胞的迁移和CuSO4线粒体功能。此外,2′-羟基查尔酮还能降低炎症因子和氧化应激水平。2′-羟基查耳酮明显抑制白细胞介素-1β和白细胞介素- tnf -α的表达,降低COX2的表达。在炎症期间观察到靶蛋白TRPV1水平的增加。讨论:实验结果验证了2′-羟基查尔酮的抗炎和抗氧化活性,初步证实了该靶点对斑马鱼行为和氧化应激水平的影响。
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来源期刊
Drug Design, Development and Therapy
Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY
CiteScore
9.00
自引率
0.00%
发文量
382
审稿时长
>12 weeks
期刊介绍: Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.
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