Modulation of PAI-1 and tPA activity and thrombolytic effects of corilagin.

In this study, Charlton's and Tomihisa's methods were modified to investigate the thrombolytic effect of corilagin from the Chinese herbal plant Phyllanthus urinaria L., as well as its effect on carotid artery patency status. The activity of type 1 plasminogen activator inhibitor (PAI-1) in rat plasma or platelet-released substances and tissue-type plasminogen activator (tPA) in rat plasma was assayed by use of a chromogenic substrate. The results showed that corilagin had a dose-dependent thrombolytic effect in rats. 5 mg/kg of corilagin produced a nearly similar reperfusion rate to that of 20000 U/kg of urokinase, whereas it produced a lower reocclusion rate than urokinase. Corilagin significantly inhibited PAI-1 activity in rat plasma or platelet-released substances while it elevated plasma tPA activity, in a concentration-dependent manner. Corilagin, however, had no influence on rabbit platelet aggregation. It is indicated that corilagin inhibited PAI-1 activity and increased tPA activity, and this property of corilagin is assumed to be responsible for the thrombolytic effect. Abbreviations. PO:persistent occlusion CR:cyclic reflow PP:persistent patency PAI-1:type 1 plasminogen activator inhibitor tPA:tissue-type plasminogen activator PBS:phosphate buffer solution IC (50):50 % of inhibitory concentration PRP:platelet-rich plasma ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet-activating factor