Evaluation on antithrombotic effect of aspirin eugenol ester from the view of platelet aggregation, hemorheology, TXB2/6-keto-PGF1α and blood biochemistry in rat model.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Ning
N
Ma
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Xi-Wang
XW
Liu
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Ya-Jun
YJ
Yang
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Dong-Shuai
DS
Shen
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Xiao-Le
XL
Zhao
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Isam
I
Mohamed
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China.
Xiao-Jun
XJ
Kong
Key Lab of New Animal Drug Project, Gansu Province, Lanzhou, 730050, People's Republic of China. lijy1971@163.com.|Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, 730050, People's Republic of China. lijy1971@163.com.|Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS, Lanzhou, 730050, People's Republic of China. lijy1971@163.com.|No.335, Jiangouyan, Qilihe District, Lanzhou, 730050, China. lijy1971@163.com.
Jian-Yong
JY
Li
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001774:Blood Chemical Analysis; D005054:Eugenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018056:Hemorheology / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D013928:Thromboxane A2 / Q000097:blood*
D005343:Fibrinolytic Agents; C575435:aspirin eugenol ester; D005054:Eugenol; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin
Aspirin eugenol ester (AEE); Blood viscosity; Platelet aggregation; Rat; Thrombosis; k-carrageenan