Planta Med 2003; 69(7): 605-609
DOI: 10.1055/s-2003-41116
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Effects of Plumbagin on Platelet Aggregation and Platelet-Neutrophil Interactions

Zhiqiang Shen1 , 2 , Zejun Dong1 , Peng Cheng2 , Ling Li2 , Zhihe Chen2 , Jikai Liu1
  • 1Kunming Institute of Botany, The Chinese Academy of Sciences, Kunming, P. R. China
  • 2Yunnan Pharmacological Laboratories of Natural Products, Kunming Medical College, Kunming, P. R. China
This project was supported by National Natural Science Foundation of China (39969005, 30225048)
Further Information

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

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

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