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

Key words

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

References

• 1 Hoylaerts M, Rijken D C, Lijnen H R, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator: role of fibrin.  J Biol Chem. 1982;  257 2912-9
• 2 Tomihisa K, Masao K, Seiji K, Hiroshi G, Toichi T, Yoshiki Y, Chuichi K. Thrombolytic activity of a novel modified tissue-type plasminogen activator, YM866, in a canine model of coronary artery thrombosis.  Jpn J Pharmacol. 1993;  63 9-16
• 3 Sancho E, Declerk P J, Price N C, Kelly S M, Booth N A. Conformational studies on plasminogen activator inhibitor (PAI-1) in active, latent, substrate and cleaved forms.  Biochemistry. 1995;  34 1064-9
• 4 Torr-Brown S R, Sobel B E. Attenuation of thrombolysis by release of plasminogen activator inhibitor type-1 from platelets.  Thromb Res. 1993;  72 413-21
• 5 An X G, Han Z C, Wang P X, Wu H Z, Zhou L L. Study on the relationship between plasminogen activator inhibitor-1 levels and acute myocardial infarction.  Chinese J Cardiovasol. 2001;  6 71-4
• 6 Thogersen A M, Jansson J H, Boman K. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor.  Circulation. 1998;  98 2241-7
• 7 Dictionary of Chinese Traditional M edicine. Shanghai; 1977: pp. 1496-7
• 8 Cheng J T, Lin T C, Hsu F L. Antihypertensive effect of corilagin in the rat.  Can J Physiol Pharmacol. 1995;  73 1425-9
• 9 Satomi H, Umemura K, Ueno A, Hatano T, Okuda T, Noro T. Carbonic anhydrase inhibitors from the pericarps of Punica granatum L.  Biol Pharm Bull. 1993;  16 787-90
• 10 Xu H X, Wan M, Dong H, But P P, Foo L Y. Inhibitory activity of flavonoids and tannins against HIV-1 protease.  Biol Pharm Bull . 2000;  23 1072-6
• 11 Liu J K, Huang Y, Henkel T, Weber K. One step purification of corilagin and ellagic acid from Phyllanthus urinaria using high-speed countercurrent chromatography.  Phytochem Analysis. 2002;  13 1-3
• 12 Yoshida T, Itoh H, Matsunaga S, Tanaka R, Okuda T. Tannins and related polyphenols of Euphorbiaceous plants.  Chem Pharm Bull. 1992;  40 53-60
• 13 Charlton P A, Faint R W, Bent F, Bryans J, Chicarelli-Robinson I, Mackie I, Machin S, Bevan P. Evaluation of a low molecular weight modulator of human plasminogen activator inhibitor-1 activity.  Thromb Haemostasis. 1996;  75 808-15
• 14 Tomihisa K, Masso K, Seiji K, Hiroshi G, Toichi T, Yoshiki Y, Chuichi K. Thrombolysis with intracoronary administration of YM866, a novel modified tissue-type plasminogen activator, in a canine model of coronary artery thrombosis.  Jpn J Pharmacol. 1993;  63 319-25
• 15 Born G VR. Aggregation of blood platelets by adenosine diphosphate and its reversal.  Nature. 1962;  194 927-9
• 16 Biemond B J, Levi M, Coronel R, Janse M J, ten Cate J W, Pannekoek H. Thrombolysis and reocclusion in experimental jugular vein and coronary artery thrombosis - effects of a plasminogen activator inhibitor type 1-neutralizing monoclonal antibody.  Circulation. 1995;  91 1175-81
• 17 Fay W P, Shapiro A D, Shih J L, Schleef R R, Ginsburg D. Complete deficiency of plasminogen activator inhibitor type-1 due to a frame-shift mutation.  New Engl J Med. 1992;  327 1729-33
• 18 Liu J K, Henkel T. Traditional Chinese Medicine (TCM): Are polyphenols and saponins the key ingredients triggering biological activities?.  Curr Med Chem. 2002;  9 1483-5