Anti-thrombotic Activity Of Benzyl Phenol Oxime

Objective: Paeonol sand its derivatives have extensive pharmacological activities.Benzyl Paeonol Oxime(BPO)was found to have an antiplatelet aggregation effect during the antipalelet activity screening of paeonol derivatives.This paper was to investigate the antithrombotic activity of BPO in vivo and in vitro and its possible mechanism.Methods: The effects of BPO on plasma prothrombin time(PT),activated partial thrombin activity time(APTT)and thrombin time(TT)in rabbits were investigated by ACL elite pro automatic coagulation factor analyzer.The effects of BPO on ADP,AA,thrombin and collagen-induced platelet aggregation were detected by turbidimetry.Ferric chloride-induced thrombosis model and Arteriovenous shunt thrombosis model in rats were performed to investigate the effect of BPO on thrombosis in rats.The concentrations of plasma protein C(PC),protein S(PS),antithrombin Ⅲ(AT-Ⅲ),GPIIb/IIIa and c AMP in plasma of rats were detected by ELISA.To study the inhibitory effect of BPO on fibrinogen/GPIIb/IIIa test.This study evaluated the cytotoxicity and bleeding risk of BPO by MTT method and tail bleeding in mice.Results: The anticoagulation test showed that BPO had a delayed effect on APTT,but no significant effect on PT and TT.In the antiplatelet aggregation experiment,BPO had an inhibitory effect on platelet aggregation induced by ADP,AA and collagen,but had no obvious inhibitory effect on thrombin induced platelet aggregation.Ferric chloride-induced thrombosis model and arteriovenous shunt thrombosis model in rats showed that BPO could reduce the weight of thrombosis in rats.ELISA experiments showed that BPO increased the concentration of PC and GPIIb/IIIa in plasma,reduce the concentrations of antithrombin Ⅲ(AT-Ⅲ)concentrations,but did not change protein S(PS)and c AMP;The experiments of fibrinogen and GPIIb/IIIa showed that BPO inhibited the binding of fibrinogen and GPIIb/IIIa.The MTT method and tail bleeding in mice showed that BPO had no cytotoxicity and showed little bleeding risk at effective dose.Conclusion: BPO has good anticoagulant activity and antiplatelet aggregation activity,its anticoagulant mechanism may be related to enhance PC activity and promote the AT-Ⅲ combined with thrombin;The mechanism of antiplatelet aggregation may be related to inhibiting the binding of fibrinogen and GPIIb/IIIa.