Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy of Agricultural Sciences, Lanzhou 730050, PR China; College of Veterinary Medicine, Agricultural University of Hebei, Baoding, Hebei 071000, PR China.
Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy of Agricultural Sciences, Lanzhou 730050, PR China.
J Proteomics. 2020 Mar 20;215:103631. doi: 10.1016/j.jprot.2019.103631. Epub 2019 Dec 28.
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.
阿司匹林丁香酚酯（AEE）是一种新型药物化合物，通过阿司匹林和丁香酚的结合合成。AEE 在角叉菜胶诱导的大鼠尾血栓模型中已被证实具有抗血栓作用。然而，其机制尚不清楚。本研究采用蛋白质组学和代谢组学相结合的综合方法，分别检测了 AEE、阿司匹林和丁香酚预处理血栓大鼠的血浆中蛋白质和代谢物的图谱。在得分图中发现不同组的血浆代谢谱明显分离。发现与脂肪酸、能量和氨基酸代谢相关的 15 种代谢物。在对照组、AEE 组、阿司匹林组和丁香酚组中分别鉴定出 144、38、41 和 54 个差异丰度蛋白（DAP）。蛋白质组学结果表明，阿司匹林调节氨基酸代谢中的 7 种蛋白和补体系统中的 4 种蛋白；丁香酚调节与凝血级联和纤维蛋白原相关的 8 种蛋白；AEE 改善 TCA 循环中的 3 种蛋白和脂质代谢中的 3 种蛋白。综合分析表明，AEE 通过改善脂肪酸、能量和脂质代谢来抗血栓形成。本研究结果表明，AEE 对血栓形成的作用机制与阿司匹林和丁香酚不同，有助于了解 AEE 对血栓形成的作用机制。意义：血栓形成是对人类健康的威胁，急需新药。在这项研究中，与模型组相比，AEE 治疗大鼠的血浆代谢谱明显分离；挑选出 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也揭示了 AEE、阿司匹林和丁香酚在血栓形成方面的不同作用机制。本研究为进一步评估 AEE 对血栓形成治疗的成药性奠定了基础。
