Modulation of PAI-1 and tPA Activity and Thrombolytic Effects of Corilagin

Abstract

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 20 000 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

IC₅₀:50 % of inhibitory concentration

PRP:platelet-rich plasma

ADP:adenosine diphosphate

AA:arachidonic acid

PAF:platelet-activating factor

Corilagin - thrombolysis - type 1 plasminogen activator inhibitor - tissue-type plasminogen activator - Phyllanthus urinaria - Euphorbiaceae

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