In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphos...In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate （ADP）, thrombin, arachidonic acid （AA） and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an ICs0 value of 899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B （2-10 mg/kg, ig） significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8-14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.展开更多
基金Natural Science Foundation of China (Grant No.813 02763)Beijing Natural Science Foundation (Grant No.7144218)
文摘In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate （ADP）, thrombin, arachidonic acid （AA） and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an ICs0 value of 899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B （2-10 mg/kg, ig） significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8-14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.
