Plasma metabonomics and proteomics studies on the anti-thrombosis mechanism of aspirin eugenol ester in rat tail thrombosis model

Abstract 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.