Anti-thrombotic effects of higenamine.

The anti-platelet and anti-thrombotic effects of higenamine, a benzyltetrahydroisoquinoline alkaloid of the roots of Aconitum japonicum (Ranunculaceae), were investigated. The degree of platelet aggregation was measured with platelet rich plasma (PRP). An acute thrombotic condition was induced in mice by the injection of the mixture of collagen and epinephrine. The thrombus formation was induced inside the arterio-venous shunt tube installed between an abdominal aorta and the renal vein of rats. Higenamine showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. It was more inhibitory to epinephrine induced aggregation (IC(50); 19 and 7.2 microM to human and rat platelets respectively) than ADP- or collagen-induced aggregation. The anti-thrombotic effects of higenamine were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV-shunt) models. The oral administration of higenamine (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV-shunt tube in rats.