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 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

Multidirectional Effects of Tormentil Extract on Hemostasis in Experimental Diabetes

“…It has been shown that procyanidins and ellagitannins exert multidirectional effects on hemostasis; however, most of these studies have been conducted in vitro , which makes it difficult to predict the activity of this class of compounds after oral intake. The effect of ellagitannins on platelet activity, coagulation, and fibrinolysis was mainly studied in vitro by using plasma ( Dong et al, 1998 ), washed platelets ( Shen et al, 2003 ), and chromogenic substrates ( Zhang et al, 2004 ; Yamamoto et al, 2011 ). The effects of ellagitannin-rich products other than TE on hemostasis has also been studied in humans after oral intake.…”

Anti-inflammatory and anti-oxidative effects of corilagin in a rat model of acute cholestasis

“…[12]. Recent research indicated that corilagin has multiple activities including antioxidative, antiinflammatory, antiapoptotic, hepatoprotective and others.…”

Tannins as Hemostasis Modulators

“…It has been shown that corilagin (ellagitannin, 7.5–60 µM) isolated from a methanolic extract obtained from the aerial parts of Phyllanthus urinaria L. (Phyllanthaceae) increased t-PA activity and decreased PAI-1 activity in plasma collected from healthy rats and also reduced the activity of PAI-1 released from thrombin-stimulated rat platelets in vitro ( Shen et al, 2003 ). The bioavailability of corilagin after oral administration to rats was 10.7% ( Zheng et al, 2016 ).…”

“…The findings of these studies indicate that the overall effect of the studied extract on thrombosis might vary depending on the pathological condition. Contrary to the P. erecta extract, corilagin injected after thrombus formation exhibited thrombolytic effect in rats which indicates its therapeutic potential ( Shen et al, 2003 ).…”