Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats.
Because shikimic acid is the key intermediate in the shikimate pathway in plants and microorganisms, shikimic acid and its derivatives have been described as herbicides and anti-microbial agents. Triacetylshikimic acid (TSA) is an acetylate derivative of shikimic acid. The possible anti-platelet activity and anti-thrombotic efficacy of TSA were evaluated and its effect on arachidonic acid (AA) metabolism and second messengers including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) was evaluated. After oral pretreatment with TSA, adenosine diphosphate (ADP)-, collagen-, and AA-induced rat platelet aggregation was inhibited ex vivo in a dose-dependent manner. In an arteriovenous-shunt thrombosis model, oral administration of TSA resulted in a dose-dependent inhibition of thrombus growth. TSA markedly increased the cAMP level and showed no effect on the cGMP level in rat platelets. Also, no significant changes in ADP-induced thromboxane B2 formation in rat platelets or 6-keto-prostaglandin F 1alpha production from the abdominal aorta were observed after oral administration of low and medium doses of TSA (12.5 and 50 mg/kg). Additionally, prothrombin time, activated partial thromboplastin time, and thrombin time were unchanged at effective anti-platelet doses of TSA. These results demonstrate that TSA exerts oral anti-platelet and anti-thrombotic efficacy without perturbation of systemic hemostasis in rats, which was partially concerned with the elevation of cAMP in platelets.
Huang
Fengyang
F
Pharmacobiology Department, CINVESTAV-I.P.N., Mexico City, Mexico. f_y_huang@yahoo.com
Xiu
Qiuping
Q
Sun
Jianning
J
Hong
Enrique
E
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D008297:Male; D010314:Partial Thromboplastin Time; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011517:Prothrombin Time; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012765:Shikimic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013918:Thrombin Time; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; C452560:triacetylshikimic acid; D012765:Shikimic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000242:Cyclic AMP; D006152:Cyclic GMP; D001241:Aspirin