aspirin-eugenol-ester and Thrombosis

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.

Topics: Animals; Aspirin; Eugenol; Metabolomics; Pharmaceutical Preparations; Proteomics; Rats; Tail; Thrombosis

Based on the prodrug principle, aspirin and eugenol, as starting precursors, were esterified to synthesize aspirin eugenol ester (AEE). The aim of the present study was to evaluate the antithrombotic effect of AEE in an animal disease model. In order to compare the therapeutic effects of AEE and its precursors, aspirin, eugenol and a combination of aspirin and eugenol were designed at the same molar quantities as the AEE medium dose in the control group.. After oral administration of AEE (dosed at 18, 36 and 72 mg/kg) for seven days, rats were treated with k-carrageenan to induce tail thrombosis. Following the same method, aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5 % CMC-Na (30 mg/kg) were administered as control drug. Different drug effects on platelet aggregation, hemorheology, TXB2/6-keto-PGF1α ratio and blood biochemistry were studied.. AEE significantly inhibited ADP and AA-induced platelet aggregation in vivo. AEE also significantly reduced blood and plasma viscosity. Moreover, AEE down-regulated TXB2 and up-regulated 6-keto-PGF1α, normalizing the TXB2/6-keto-PGF1α ratio and blood biochemical profile. In comparison with aspirin and eugenol, AEE produced more positive therapeutic effects than its precursors under the same molar quantity.. It may be concluded that AEE was a good candidate for new antithrombotic and antiplatelet medicine. Additionally, this study may help to understand how AEE works on antithrombosis in different ways.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Aspirin; Blood Chemical Analysis; Eugenol; Fibrinolytic Agents; Hemorheology; Male; Platelet Aggregation; Rats; Rats, Wistar; Thrombosis; Thromboxane A2

Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

Topics: Adenosine Diphosphate; Animals; Aspirin; Blood Platelets; Carrageenan; Disease Models, Animal; Erythrocyte Count; Erythrocytes; Eugenol; Fibrinogen; Hemoglobins; Male; Platelet Aggregation Inhibitors; Platelet Count; Prothrombin Time; Rats; Rats, Wistar; Thrombosis