Subscribe to RSS
DOI: 10.1055/s-2007-967177
© Georg Thieme Verlag KG Stuttgart · New York
Antiplatelet Activity of Geranylgeraniol Isolated from Pterodon pubescens Fruit Oil is Mediated by Inhibition of Cyclooxygenase-1
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