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Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Ma N, Liu XW, Yang YJ, Li JY, Mohamed I, Liu GR, Zhang JY - PLoS ONE (2015)

Bottom Line: Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol.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).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.

View Article: PubMed Central - PubMed

Affiliation: 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 CAAS, Lanzhou, 730050, P. R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Decreasing effect of AEE on the concentration of FIB in κ-carrageenan-induced rat tail thrombosis model (n = 10).After the last measurement of thrombosis length, serum samples were got for coagulation parameters examination. FIB: fibrinogen. Integration: integration of aspirin and eugenol (molar ratio 1:1). ##P< 0.01, #P< 0.05 significant difference from model group. aaP<0.01, aP< 0.05, significant difference from CMC-Na group. bbP< 0.01, bP< 0.05, significant difference from aspirin group. ccP< 0.01, cP< 0.05, significant difference from eugenol group.
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pone.0133125.g003: Decreasing effect of AEE on the concentration of FIB in κ-carrageenan-induced rat tail thrombosis model (n = 10).After the last measurement of thrombosis length, serum samples were got for coagulation parameters examination. FIB: fibrinogen. Integration: integration of aspirin and eugenol (molar ratio 1:1). ##P< 0.01, #P< 0.05 significant difference from model group. aaP<0.01, aP< 0.05, significant difference from CMC-Na group. bbP< 0.01, bP< 0.05, significant difference from aspirin group. ccP< 0.01, cP< 0.05, significant difference from eugenol group.

Mentions: Anticoagulant activity of AEE was evaluated by the classical coagulation assays prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB). When compared κ-carrageenan-induced tail thrombosis model group with blank group, the results showed that PT and FIB values increased and TT values reduced significantly. Compared with CMC-Na group, the PT values in aspirin, medium- and high-dose AEE groups were decreased significantly (P< 0.01) (seen in Table 2). For TT values, the results in aspirin, eugenol, low- and medium-dose AEE groups were similar to the CMC-Na group. However, the TT values in high-dose AEE group and integration of aspirin and eugenol (ratio 1:1) group were decreased in comparison with CMC-Na group. In addition, the PT and TT values in AEE groups were dose-independent. The concentration values of FIB in eugenol, AEE and integration groups were significantly decreased in comparison with model group (seen in Fig 3).


Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Ma N, Liu XW, Yang YJ, Li JY, Mohamed I, Liu GR, Zhang JY - PLoS ONE (2015)

Decreasing effect of AEE on the concentration of FIB in κ-carrageenan-induced rat tail thrombosis model (n = 10).After the last measurement of thrombosis length, serum samples were got for coagulation parameters examination. FIB: fibrinogen. Integration: integration of aspirin and eugenol (molar ratio 1:1). ##P< 0.01, #P< 0.05 significant difference from model group. aaP<0.01, aP< 0.05, significant difference from CMC-Na group. bbP< 0.01, bP< 0.05, significant difference from aspirin group. ccP< 0.01, cP< 0.05, significant difference from eugenol group.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4507943&req=5

pone.0133125.g003: Decreasing effect of AEE on the concentration of FIB in κ-carrageenan-induced rat tail thrombosis model (n = 10).After the last measurement of thrombosis length, serum samples were got for coagulation parameters examination. FIB: fibrinogen. Integration: integration of aspirin and eugenol (molar ratio 1:1). ##P< 0.01, #P< 0.05 significant difference from model group. aaP<0.01, aP< 0.05, significant difference from CMC-Na group. bbP< 0.01, bP< 0.05, significant difference from aspirin group. ccP< 0.01, cP< 0.05, significant difference from eugenol group.
Mentions: Anticoagulant activity of AEE was evaluated by the classical coagulation assays prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB). When compared κ-carrageenan-induced tail thrombosis model group with blank group, the results showed that PT and FIB values increased and TT values reduced significantly. Compared with CMC-Na group, the PT values in aspirin, medium- and high-dose AEE groups were decreased significantly (P< 0.01) (seen in Table 2). For TT values, the results in aspirin, eugenol, low- and medium-dose AEE groups were similar to the CMC-Na group. However, the TT values in high-dose AEE group and integration of aspirin and eugenol (ratio 1:1) group were decreased in comparison with CMC-Na group. In addition, the PT and TT values in AEE groups were dose-independent. The concentration values of FIB in eugenol, AEE and integration groups were significantly decreased in comparison with model group (seen in Fig 3).

Bottom Line: Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol.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).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.

View Article: PubMed Central - PubMed

Affiliation: 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 CAAS, Lanzhou, 730050, P. R. China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus