Subscribe to RSS
DOI: 10.1055/s-2003-41116
© Georg Thieme Verlag Stuttgart · New York
Effects of Plumbagin on Platelet Aggregation and Platelet-Neutrophil Interactions
This project was supported by National Natural Science Foundation of China (39969005, 30225048)Publication History
Received: November 21, 2002
Accepted: March 22, 2003
Publication Date:
04 August 2003 (online)
Abstract
The effects of plumbagin were investigated on platelet aggregation in vitro and ex vivo, on the binding of thrombin-stimulated platelets to neutrophils, and platelet aggregation induced by intact neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF) activated neutrophils, by use of the methods of Hamburger, McEver and Born, respectively. The results showed that plumbagin in vitro significantly inhibited adenosine diphosphate (ADP)-, arachidonic acid (AA)-, or platelet activating factor (PAF)-induced platelet aggregation, in a concentration-dependent manner. The medium inhibitory concentrations (IC50) were 39.4, 82.7 and 38.1 μM, respectively. Intragastric plumbagin at 10 mg/kg markedly suppressed platelet aggregation induced by ADP, AA, or PAF. Plumbagin decreased the binding between thrombin-stimulated platelets and neutrophils with an IC50 of 62.9 μM. Plumbagin significantly inhibited washed platelet aggregation stimulated by fMLP- or PAF-activated neutrophils. The IC50 values were 54.3 and 47.6 μM, respectively. On the other hand, plumbagin and aspirin increased the inhibition of intact neutrophils on AA-induced platelet aggregation. It is suggested that plumbagin inhibited platelet aggregation in vitro and ex vivo, suppressed the binding of activated platelets to neutrophils, inhibited platelet aggregation induced by activated neutrophils, and increased inhibition of intact neutrophils on platelet reactivity.
Abbreviations
DMSO:dimethyl sulphoxide
fMLP:N-formyl-methionyl-leucyl-phenylalanine
ADP:adenosine diphosphate
AA:arachidonic acid
PAF:platelet activating factor
Key words
Plumbagin - platelet aggregation - platelet-neutrophil interactions
References
- 1 Bendnar M, Smith B, Pinto A, Mullane K. Neutrophil depletion suppresses 111In-labelled platelet accumulation in infracted myocardium. J Cardiovasc Pharmacol. 1985; 7 906-8
- 2 Lin Y, Wang Z. Platelet-neutrophil interaction in acute myocardial ischemia rate. Basic Med Sci Clin. 1997; 17 376-80
- 3 Ott I, Neumann F J, Gawaz M, Schmitt M, Schomig A. Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation. 1996; 94 1239-46
- 4 Krishnaswamy M, Purushothaman K K. Plumbagin: a study of its anticancer, antibacterial and antifungal properties. Ind J Exp Biol. 1980; 18 876-977
- 5 Sidhu G S, Sankaram A VB. New biplumbagin and 3-chloroplumbagin from Plumbago zeylanica . Tetrahedron Lett. 1971; 26 2385-8
- 6 Sankaram A VB, Narayana V V, Marthandamurthi M. 13C NMR spectra of some natural occurring binaphthoquinones and related compounds. Phytochemistry. 1986; 25 2867-71
- 7 Hamburger S A, McEver R P. GMP-140 mediates adhesion of stimulated platelets to neutrophils. Blood. 1990; 75 550-4
- 8 Born G VR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962; 194 927-9
- 9 Hourani S MO, Hall D A. Receptors for ADP on human blood platelets. TIPS. 1994; 15 103-8
- 10 Karen L KK, Alaina J A, Van H T, Colin C D, Basil D R. Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation. Thromb Res. 2001; 103 387-97
- 11 Snyder F. PAF and related acetylated lipids as potent biologically active cellular mediators. Am J Physiol. 1990; 259 697-701
- 12 Stenberg P E, Mcever R P, Shuman M A, Jacques Y V, Bainton D F. A platelet alpha-granule membrane protein (GMP-140) is expressed on plasma membrane after activation. J Cell Biol. 1985; 101 880-3
- 13 Robert F S, Heather M J, Robert G W, Stan H. Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin. Thrombosis and Haemostasis. 2002; 88 488-94
- 14 Marcus A J, Safier L B. Thromboregulation: multicellular modulation of platelet reactivity in haemostasis and thrombosis. FASEB J. 1993; 7 516-22
- 15 Maschio A D, Evangelista V, Rajtar G, Chen Z M, Cerletti C, Gaetano G. Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents. Am J Physiol. 1990; 258 H870-H9
- 16 Gaetano G, Evangelista V, Rajtar G, Del Maschio A, Cerletti C. Activated polymorphonuclear leukocytes stimulate platelet function. Thromb. Res.. 1990; (Suppl. XI) 25-32
- 17 Premakumari P, Rathinam K, Santhakumari G. Antifertility activity of plumbagin. Ind J Med Res. 1977; 65 829-38
Dr. Jikai Liu
Kunming Institute of Botany
The Chinese Academy of Sciences
Kunming 650204
P. R. China
Phone: +86-871-5216327
Fax: +86-871-5150227
Email: jkl@public.km.yn.cn