Planta Med 2007; 73(5): 480-483
DOI: 10.1055/s-2007-967177
Letter
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Antiplatelet Activity of Geranylgeraniol Isolated from Pterodon pubescens Fruit Oil is Mediated by Inhibition of Cyclooxygenase-1

Nivea Oliveira Calixto1 , 2 , Maria Cristina da Costa e Silva1 , Carlos Roberto Machado Gayer1 , Marsen Garcia Pinto Coelho1 , Márcia Cristina Paes1 , Adriane Regina Todeschini2
  • 1Departamento de Bioquímica, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
  • 2Laboratório de Glicobiologia, Instituto de Biofísica Carlos Chagas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Further Information

Publication History

Received: December 10, 2006 Revised: March 6, 2007

Accepted: March 12, 2007

Publication Date:
18 April 2007 (online)

Abstract

Geranylgeraniol is a natural isoprenoid with anti-inflammatory properties extracted from the Pterodon pubescens Benth. fruit oil (PpO). In this work, the antiplatelet effect of both PpO and geranylgeraniol is investigated. ADP-, thrombin- and arachidonic acid (AA)-induced aggregation in human and rabbit platelets showed a prime involvement of PpO and geranylgeraniol in the arachidonic acid cascade. The lack of any significant inhibition of platelet aggregation induced by U-46 619 and thrombin, associated with PpO and geranylgeraniol suppression of prostaglandin E2 and thromboxane A2 formation demonstrate, for the first time, the involvement of geranylgeraniol in the AA metabolisation by inhibiting the cyclooxygenase enzyme.

Abbreviations

ADP:adenosine diphosphate

AA:arachidonic acid

COX:cyclooxygenase

PG:prostaglandin

PpO:Pterodon pubescens fruits oil

PPP:platelet poor plasma

PRP:platelet rich plasma

RA:rheumatoid arthritis

SDM:standard deviation of the mean

TX:thromboxane

TXS:thromboxane synthase

References

  • 1 von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease.  Circ Res. 2007;  100 27-40.
  • 2 Bos C L, Richel D J, Ritsema T, Peppelenbosch M P, Versteeg H H. Prostanoids and prostanoid receptors in signal transduction.  Int J Biochem Cell Biol. 2004;  36 1187-205.
  • 3 Silva M CC, Gayer C RM, Lopes C S, Calixto N O, Reis P A, Passaes C PB. et al . Acute and topic anti-edematogenic fractions isolated from the seeds of Pterodon pubescens .  J Pharm Pharmacol. 2004;  B56 135-41.
  • 4 Tubaro A, Dri P, Delbello C, Zilli T, Della Loggia R. The croton oil ear test.  Agents Actions. 1985;  17 347-9.
  • 5 Cazenave J P, Benveniste J, Mustard J F. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs.  Lab Invest. 1979;  41 275-85.
  • 6 Vane J R, Botting R M. Mechanism of action of nonsteroidal anti-inflammatory drugs.  Am J Med. 1998;  104 2S-8S.
  • 7 Hata A N, Breyer R M. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation.  Pharmacol Ther. 2004;  103 47-66.
  • 8 Hiruma Y, Nakahama K, Fujita H, Morita I. Vitamin K2 and geranylgeraniol, its side chain component, inhibited osteoclast formation in a different manner.  Biochem Biophys Res Commun. 2004;  314 24-30.
  • 9 Vane J R, Bakhle Y S, Botting R M. Cyclooxygenases 1 and 2.  Annu Rev Pharmacol Toxicol. 1998;  38 97-120.
  • 10 Ronden J E, Groenen-van Dooren M MCL, Hornstra G, Vermeer C. Modulation of arterial thrombosis tendency in rats by vitamin K and its side chains.  Atherosclerosis. 1997;  132 61-7.
  • 11 Resh M D. Trafficking and signaling by fatty-acylated and prenylated proteins.  Nat Chem Biol. 2006;  2 584-90.
  • 12 Huzoor-Akbar , Wang W, Kornhauser R, Volker C, Stock J B. Protein prenylcysteine analog inhibits agonist-receptor-mediated signal transduction in human platelets.  Proc Natl Acad Sci USA. 1993;  90 868-72.
  • 13 Rosado J A, Sage S O. Farnesylcysteine analogues inhibit store-regulated Ca2+ entry in human platelets: evidence for involvement of small GTP-binding proteins and actin cytoskeleton.  Biochem J. 2000;  347 183-92.
  • 14 Nakano T, Matsumoto S, Hanasaki K, Arita H. Platelet activation by tetraprenol via stimulation of phospholipase A2 action.  J Biochem (Tokyo). 1989;  106 887-93.
  • 15 Coelho L P, Reis P A, Castro F L, Gayer C RM, Lopes C S, Silva M CC. et al . Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds.  J Ethnopharmacol. 2005;  98 109-16.
  • 16 Born G VR, Cross M J. The aggregation of blood platelets.  J Physiol. 1963;  168 178.
  • 17 Pollock W K, Sage S O, Rink T J. Stimulation of Ca2+ efflux from fura-2-loaded platelets activated by thrombin or phorbol myristate acetate.  FEBS Lett. 1987;  210 132-6.
  • 18 Grynkiewicz G, Poenie M, Tsien R Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties.  J Biochem Chem. 1985;  260 3440-50.

Prof. Dr. Adriane Regina Todeschini

Laboratório de Glicobiologia

Instituto de Biofísica Carlos Chagas

Centro de Ciências da Saúde - Bloco G

Universidade Federal do Rio de Janeiro

Cidade Universitária

Ilha do Fundão

21944-970 Rio de Janeiro, RJ

Brazil

Phone: +55-21-2562-6646

Fax: +55-21-2280-8193

Email: adrianet@biof.ufrj.br

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