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.