| Objective: To investigate the effects of verussurinine (VSRN),which was extracted from Veratrum nigrum L. var.ussuriense Nakai alkaloids (VnA), on thrombosis, hemorrheology, platelet aggregation and blood coagulation in animals in order to provide experimental basis for its development as a highly efficacious anti-thrombotic agent. Methods and Results:1. Effect of VSRN on thrombosis in rats1.1 The anti-artery thrombosis effect of VSRN in ratsElectricity-induced carotid thrombosis model was used to examine anti-arterial thrombosis effect of VSRN. The occlusion time (OT) was recorded. The results showed that VSRN 1.25,2.5,5.00,10.00,20.00μg﹒kg-1 and LAS18000μg. kg-1 prolonged the OT by 21.93%,26.23%,47.63%,28.01%和7.76%..1.2. Effect of VSRN on venous thrombosis in ratsThe blood stasis-induced inferior vena cava thrombosis model was made according to Reyers, method. The effect of VSRN was evaluated in terms of thrombus formation rate and the decrease in thrombus dry weight .NS was given as negative control while heparin as positive control .The results showed that VSRN 1.25,2.5,5.00,10.00,20.00μg﹒kg-1 lowered thrombus formation rate and decrease by 21.91%, 42.78%, 60.00%,72.87%.and 88.17%.2. Effect of VSRN on platelet aggregation2.1 Effect of VSRN on ex vivo rat platelet aggregationThe blood were collected from rats receiving iv administration of VSRN at different doses. Platelet aggregation curves were recorded ex vivo according to the method of Born. And then the percentage of platelet aggregation was calculated .The results showed that VSRN 2.5,5.00, 10.00, 20.00μg. kg-1 lowered ADP-induced platelet aggregation by 18.50%,28.60%,49.00%和61.30%.2.2 Effect of VSRN on in vitro rat platelet aggregationThe blank blood of rats untreated with drug were collected ,platelet rich plasma(PRP) and platelet poor plasma (PPP) were prepared by routine procedures. ADP was used as platelet aggregation inducer. Platelet aggregation curves were recorded according to the method of Born. And then the percentage of platelet aggregation was calculated. The results showed that VSRN 6.25,12.50,25.00,50.0μg.L-1 lowered ADP-induced platelet aggregation by 18.50%,26.60%,44.00%和57.80%.3 Effect of VSRN on hemorrheology in rabbitsVSRN or NS was injected into the ear marginal vein of rabbits, then the blood was collected from heart. The important hemorrheological indices were measured. The results showed that, as compared with NS, VSRN 1.25,2.5,5.00,10.00,20.00μg﹒ kg-1 decrease the whole blood viscosity and plasma viscosity.4. Effect of VSRN on clotting time (CT) in ratsThe capillary glass tube method was employed to examine the effect of VSRN on CT .The CT was recorded at 20min post- dosing. The results showed that iv VSRN 1.25,2.5,5.00,10.00,20.00μg﹒ kg-1 increased CT by 13.18%,38.60% and 48.70%,respectively.5. Effect of VSRN on bleeding time (BT) in ratsThe mouse tail transection method was used to examine effect of VSRN on BT . The BT was recorded at 20 min after iv administration. The results showed that VSRN 1.25,2.5,5.00,10.00,20.00μg﹒ kg-1 prolonged BT by 20.81%,40.43% and 49.25%。Conclusion: VSRN has powerful anti-thrombotic effects on artery thrombosis and venous thrombosis in rats, which are related to its antiplatelet, anticoagulant and blood viscosity-lowering effects; VSRN is one of the important antithrombolic compounds of VnA. |
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