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Plasma metabonomics and proteomics studies on the anti-thrombosis mechanism of aspirin eugenol ester in rat tail thrombosis model.
Journal of Proteomics ( IF 3.3 ) Pub Date : 2019-12-28 , DOI: 10.1016/j.jprot.2019.103631
Ning Ma 1 , Yajun Yang 2 , Xiwang Liu 2 , Shihong Li 2 , Zhe Qin 2 , Jianyong Li 2
Affiliation  

Aspirin eugenol eater (AEE), a new drug compound, was synthesized through the combination of aspirin and eugenol. Antithrombotic effects of AEE have been confirmed in carrageenan-induced rat tail thrombosis model. However, its mechanism is unclear. With the application of integrated approach combining proteomics and metabolomics, the profilings of protein and metabolite in plasma were examined in thrombosis rat pretreated with AEE, aspirin and eugenol, respectively. A clear separation of the plasma metabolic profiles from different groups was found in score plots. 15 metabolites related with the metabolism of fatty acid, energy and amino acid were found. A total of 144, 38, 41 and 54 differentially abundant proteins (DAPs) were identified in control, AEE, aspirin and eugenol group, respectively. Proteomic results showed that aspirin modulated 7 proteins in amino acid metabolism and 4 proteins in complement system; eugenol regulated the 8 proteins related with coagulation cascades and fibrinogen; AEE improved 3 proteins in TCA cycle and 3 in lipid metabolism. Integrated analysis suggested that AEE improved fatty acid, energy and lipid metabolism to against thrombosis. Results of this study indicated AEE had different action mechanism on thrombosis from aspirin and eugenol, and contribute to understanding the mechanisms of AEE on thrombosis.

Significance

Thrombosis is a threat to human health, and there is an urgent need for new drug. In this study, compared with the model group, plasma metabolic profiles in AEE-treated rats were clearly separated; 15 metabolites and 38 proteins were picked out. These metabolites and proteins may assist in understanding the action mechanism of AEE on thrombosis. The results of plasma metabonomics and proteomics also revealed the different action mechanism among AEE, aspirin and eugenol on thrombosis. This study established the foundation to further evaluate the druggability of AEE on thrombosis treatment.



中文翻译:

阿司匹林丁子香酚酯在大鼠尾部血栓形成模型中抗血栓形成机理的血浆代谢组学和蛋白质组学研究。

阿司匹林丁香油食用者(AEE)是一种新的药物化合物,是通过阿司匹林和丁香酚的组合合成的。在角叉菜胶诱导的大鼠尾部血栓形成模型中已经证实了AEE的抗血栓形成作用。但是,其机制尚不清楚。应用蛋白质组学和代谢组学相结合的综合方法,分别检测了用AEE,阿司匹林和丁香酚预处理的血栓形成大鼠血浆中蛋白质和代谢物的分布。在评分图中发现了血浆代谢曲线与不同组的清晰分离。发现了15种与脂肪酸,能量和氨基酸代谢有关的代谢物。在对照组,AEE,阿司匹林和丁子香酚组中分别鉴定出总共144、38、41和54个差异丰富的蛋白质(DAP)。蛋白质组学结果显示,阿司匹林调节氨基酸代谢中的7种蛋白质和补体系统中的4种蛋白质。丁子香酚调节与凝血级联反应和纤维蛋白原有关的8种蛋白质。AEE在TCA循环中改善了3种蛋白质,在脂质代谢中改善了3种。综合分析表明,AEE可改善脂肪酸,能量和脂质代谢,从而抵抗血栓形成。这项研究的结果表明,AEE对血栓形成的作用机理不同于阿司匹林和丁香酚,并有助于了解AEE对血栓形成的机理。能量和脂质代谢以对抗血栓形成。研究结果表明,AEE对血栓形成的作用机制与阿司匹林和丁子香酚不同,并且有助于理解AEE对血栓形成的机制。能量和脂质代谢以对抗血栓形成。这项研究的结果表明,AEE对血栓形成的作用机理不同于阿司匹林和丁香酚,并有助于了解AEE对血栓形成的机理。

意义

血栓形成对人类健康构成威胁,因此迫切需要新药。在这项研究中,与模型组相比,在AEE治疗的大鼠中血浆代谢谱清楚地分开了。提取了15种代谢物和38种蛋白质。这些代谢物和蛋白质可能有助于了解AEE对血栓形成的作用机制。血浆代谢组学和蛋白质组学的结果还揭示了AEE,阿司匹林和丁子香酚对血栓形成的不同作用机理。该研究为进一步评估AEE在血栓形成治疗中的可药用性奠定了基础。

更新日期:2019-12-29
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