ABSTRACT
Propyl gallate (PG) is a platelet agonist characterized by inducing platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activity. The mechanisms of platelet activation following PG stimulation were examined by pre-incubating platelets with well-defined platelet inhibitors using platelet aggregation, protein tyrosine phosphorylation, activated plasma clotting time, and annexin V binding by flow cytometry. PG-induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase, and abciximab (c7E3), suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors, and glycoprotein IIb/IIIa, respectively. The phosphorylation of the cytoskeletal enzyme pp60(c-src) increased following PG stimulation, but was blunted by pre-incubation of platelets with aspirin, apyrase, and c7E3, suggesting that tyrosine kinase is important for the signal transduction of platelet aggregation. Propyl gallate also activates platelet factor 3 by decreasing the platelet coagulation time and increasing platelet annexin V binding. Platelet incubation with aspirin, apyrase, and c7E3 did not alter PG-induced platelet coagulation and annexin V binding. The results suggest that platelet factor 3 activation and membrane phosphotidylserine expression were not involved with activation of platelet cyclooxygenase, adenosine phosphate receptors, and glycoprotein IIb/IIIa. PG is unique in its ability to stimulate platelet aggregation and coagulation simultaneously, and platelet inhibitors in this study affect only platelet aggregation but not platelet coagulation.
Subject(s)
Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Platelet Factor 3/metabolism , Propyl Gallate/pharmacology , Protein-Tyrosine Kinases/metabolism , Annexin A5/metabolism , Antioxidants/pharmacology , Apyrase/pharmacology , Aspirin/pharmacology , Humans , Phosphorylation/drug effects , Platelet Factor 3/drug effects , Proto-Oncogene Proteins pp60(c-src)/metabolismABSTRACT
OBJECTIVE: To study the effect of Erigeron breviscapus extract on anticoagulation. METHOD: Coagulation time (CT), prothrombin time (PT), platelet factor III (PF3) and euglobulin lysis time (ELT) have been used to evaluate the anticoagulation activities of Erigeron breviscapus extract. RESULT: Erigeron breviscapus extract significantly delayed CT and PT, inhibited the activity of PF3, and decreased ELT. CONCLUSION: Erigeron breviscapus extract plays an role in anticoagulation by inhibiting PF3 and prothrombin V. It can also enhance the activity of fibrimolysis.
Subject(s)
Anticoagulants/pharmacology , Drugs, Chinese Herbal/pharmacology , Fibrinolysis/drug effects , Flavonoids/pharmacology , Platelet Factor 3/drug effects , Animals , Blood Platelets/drug effects , Dose-Response Relationship, Drug , Female , Male , Mice , Plants, Medicinal/chemistry , Prothrombin Time , Rabbits , Rats , Rats, Sprague-DawleyABSTRACT
Serial platelet functions were studied after various single doses of aspirin (75 mg, 150 mg, 300 mg, and 600 mg) in 20 males. Clotting time and platelet counts remained unchanged. Significant deaggregation of platelets occurred only with 600 mg of aspirin. This persisted on day '3'. Platelet factor-3 release time was prolonged till day '3' with only 150 mg and 600 mg doses of aspirin. In view of these findings it appears that 600 mg aspirin given every 4th day is more suited for significant antiplatelet effect.
