The anti-platelet and anti-thrombotic effects of higenamine, a benzyltetrah
ydroisoquinoline 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 mi
ce by the injection of the mixture of collagen and epinephrine. The thrombu
s formation was induced inside the arterio-venous shunt tube installed betw
een an abdominal aorta and the renal vein of rats. Higenamine showed inhibi
tory activities to both human and rat platelet aggregation induced by ADP,
collagen and epinephrine. It was more inhibitory to epinephrine induced agg
regation (IC50; 19 and 7.2 muM to human and rat platelets respectively) tha
n ADP- or collagen-induced aggregation. The anti-thrombotic effects of hige
namine were also observed in both mouse acute thrombosis model and rat arte
rio-venous shunt (AV-shunt) models. The oral administration of higenamine (
50 or 100 mg/kg) increased the recovery rates from the acute thrombotic cha
llenge in mice and lowered the weight of thrombus formed inside the AV-shun
t tube in rats.