J Appl Biomed 5:105-113, 2007 | DOI: 10.32725/jab.2007.015

Urtica dioica extract reduces platelet hyperaggregability in type 2 diabetes mellitus by inhibition of oxidant production, Ca2+ mobilization and protein tyrosine phosphorylation

Mohammed El Haouari1, Isaac Jardin2, Hasane Mekhfi1, Juan A. Rosado2,*, Ginés M. Salido2
1 Laboratoire de Physiologie et Ethnopharmacologie, Département de Biologie, Université Mohamed 1er, Faculté des Sciences, Bd. Mohamed VI, BP 717, Oujda 60000, Morocco
2 Department of Physiology, Cell Physiology Research Group, University of Extremadura, 10071 Cáceres, Spain

Platelet hyperaggregability is involved in the pathogenesis of type 2 diabetes mellitus. Thrombin-evoked platelet aggregation includes the activation of several intracellular pathways, including endogenous generation of reactive oxygen species (ROS), Ca2+ mobilization and protein tyrosine phosphorylation. Here we show that crude aqueous extract from Urtica dioica reduces thrombin-evoked aggregation in platelets from healthy donors and diabetics, in a concentration-dependent manner. U. dioica extract showed a potent antioxidant activity and prevented thrombin-evoked ROS generation in platelets from healthy and diabetic donors. Treatment with U. dioica extract reduced Ca2+ entry induced by thrombin or selective depletion of the two Ca2+ stores in platelets (without altering Ca2+ release), reduced protein tyrosine phosphorylation and reversed the abnormal Ca2+ mobilization and tyrosine phosphorylation in platelets from diabetics. We conclude that extract from U. dioica shows antiaggregant actions and might be used for the treatment and/or prevention of cardiovascular complications associated with type 2 diabetes mellitus.

Keywords: platelets; type 2 diabetes mellitus; Urtica dioica; calcium mobilization; antioxidant; tyrosine phosphorylation

Received: March 21, 2007; Revised: April 23, 2007; Published: July 31, 2007  Show citation

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El Haouari M, Jardin I, Mekhfi H, Rosado JA, Salido GM. Urtica dioica extract reduces platelet hyperaggregability in type 2 diabetes mellitus by inhibition of oxidant production, Ca2+ mobilization and protein tyrosine phosphorylation. J Appl Biomed. 2007;5(2):105-113. doi: 10.32725/jab.2007.015.
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References

  1. Belton OA, Duffy A, Toomey S, Fitzgerald DJ: Cyclooxygenase isoforms and platelet vessel wall interactions in the apolipoprotein E knockout mouse model of atherosclerosis. Circulation 108:3017-3023, 2003. Go to original source... Go to PubMed...
  2. Ben-Amor N, Redondo PC, Bartegi A, Pariente JA, Salido GM, Rosado JA: A role for 5,6-epoxyeicosatrienoic acid in calcium entry by de novo conformational coupling in human platelets. J. Physiol. 570:309-323, 2006. Go to original source... Go to PubMed...
  3. Blankenship KA, Dawson CB, Aronoff GR, Dean WL: Tyrosine phosphorylation of human platelet plasma membrane Ca2+-ATPase in hypertension. Hypertension 35:103-107, 2000. Go to original source... Go to PubMed...
  4. Blann AD, Nadar S, Lip GY: Pharmacological modulation of platelet function in hypertension. Hypertension 42:1-7, 2003. Go to original source... Go to PubMed...
  5. Bnouham M, Merhfour FZ, Ziyyat A, Mekhfi H, Aziz M, Legssyer A: Antihyperglycemic activity of the aqueous extract of Urtica dioica. Fitoterapia 74:677-681, 2003. Go to original source... Go to PubMed...
  6. Dixon LJ, Hughes SM, Rooney K, Madden A, Devine A, Leahey W, Henry W, Johnston GD, McVeigh GE: Increased superoxide production in hypertensive patients with diabetes mellitus: role of nitric oxide synthase. Am. J. Hypertens. 18:839-843, 2005. Go to original source... Go to PubMed...
  7. Dogne JM, Leval XD, Benoit P, Delarge J, Masereel B, David JL: Recent advances in antiplatelet agents. Curr. Med. Chem. 9:577-589, 2002. Go to original source... Go to PubMed...
  8. El Haouari M, Bnouham M, Bendahou M, Aziz M, Ziyyat A, Legssyer A, Mekhfi H: Inhibition of rat platelet aggregation by Urtica dioica leaves extracts. Phytother. Res. 20:568-572, 2006. Go to original source... Go to PubMed...
  9. Garnier G, Bezanger-Beauquesne L, Debraux G: Ressources medicinales de la flore francaise, Vol 2, Vigot Freres, Paris 1961, pp. 962-964.
  10. Grynkiewicz G, Poenie M, Tsien RY: A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260:3440-3450, 1985. Go to original source...
  11. Jardín I, Redondo PC, Salido GM, Pariente JA, Rosado JA: Endogenously generated reactive oxygen species reduce PMCA activity in platelets from patients with non-insulin dependent diabetes mellitus. Platelets 17:283-288, 2006. Go to original source... Go to PubMed...
  12. Legssyer A, Ziyyat A, Mekhfi H, Bnouham M, Tahri A, Serhrouchni M, Hoerter J, Fischmeister R: Cardiovascular effects of Urtica dioica L. in isolated rat heart and aorta. Phytother. Res. 16:503-507, 2002. Go to original source... Go to PubMed...
  13. Lopez JJ, Redondo PC, Salido GM, Pariente JA, Rosado JA: Two distinct Ca2+ compartments show differential sensitivity to thrombin, ADP and vasopressin in human platelets. Cell. Signal. 18:373-381, 2006. Go to original source... Go to PubMed...
  14. Mandal S, Sarode R, Dash S, Dash RJ: Hyperaggregation of platelets detected by whole blood platelet aggregometry in newly diagnosed noninsulin-dependent diabetes mellitus. Am. J. Clin. Pathol. 100:103-107, 1993. Go to original source... Go to PubMed...
  15. Minuz P, Fumagalli L, Gaino S, Tommasoli RM, Degan M, Cavallini C, Lecchi A, Cattaneo M, Lechi Santonastaso C, Berton G: Rapid stimulation of tyrosine phosphorylation signals downstream of G-protein-coupled receptors for thromboxane A2 in human platelets. Biochem. J. 15:127-134, 2006. Go to original source... Go to PubMed...
  16. Pignatelli P, Pulcinelli FM, Lenti L, Gazzaniga PP, Violi F: Hydrogen peroxide is involved in collagen-induced platelet activation. Blood 91: 484-490, 1998. Go to original source...
  17. Redondo PC, Jardín I, Hernandez-Cruz JM, Pariente JA, Salido GM, Rosado JA: Hydrogen peroxide and peroxynitrite enhance Ca2+ mobilization and aggregation in platelets from type 2 diabetic patients. Biochem. Biophys. Res. Commun. 334:779-786, 2005. Go to original source... Go to PubMed...
  18. Rosado JA, Graves D, Sage SO: Tyrosine kinases activate store-mediated Ca2+ entry in human p latelets through the reorganization of the actin cytoskeleton. Biochem. J. 351:429-437, 2000. Go to original source... Go to PubMed...
  19. Rosado JA, Lopez JJ, Harper AG, Harper MT, Redondo PC, Pariente JA, Sage, SO, Salido GM: Two pathways for store-mediated calcium entry differentially dependent on the actin cytoskeleton in human platelets. J. Biol. Chem. 279:29231-29235, 2004a. Go to original source... Go to PubMed...
  20. Rosado JA, Porras T, Conde M, Sage SO: Cyclic nucleotides modulate store-mediated calcium entry through the activation of protein-tyrosine phosphatases and altered actin polymerization in human platelets. J. Biol. Chem. 276:15666-15675, 2001. Go to original source... Go to PubMed...
  21. Rosado JA, Redondo PC, Salido GM, Gomez-Arteta E, Sage SO, Pariente JA: Hydrogen peroxide generation induces pp60src activation in human platelets: evidence for the involvement of this pathway in store-mediated calcium entry. J. Biol. Chem. 279:1665-1675, 2004b. Go to original source... Go to PubMed...
  22. Rosado JA, Saavedra FR, Redondo PC, Hernández-Cruz JM, Salido GM, Pariente JA: Reduced plasma membrane Ca2+-ATPase function in platelets from patients with non-insulin-dependent diabetes mellitus. Haematologica 89:1142-1144, 2004c. Go to PubMed...
  23. Rosado JA, Sage SO: The actin cytoskeleton in store-mediated calcium entry. J. Physiol. 526: 221-229, 2000. Go to original source... Go to PubMed...
  24. Ruf JC: Alcohol, wine and platelet function. Biol. Res. 37:209-215, 2004. Go to original source... Go to PubMed...
  25. Saavedra FR, Redondo PC, Hernandez-Cruz JM, Salido GM, Pariente JA, Rosado JA: Store-operated Ca2+ entry and tyrosine kinase pp60src hyperactivity are modulated by hyperglycemia in platelets from patients with non insulin-dependent diabetes mellitus. Arch. Biochem. Biophys. 432:261-268, 2004. Go to original source... Go to PubMed...
  26. Seno T, Inoue N, Gao D, Okuda M, Sumi Y, Matsui K, Yamada S, Hirata K, Kawashima S, Tawa R, Imajoh-Ohmi S, Sakurai H, Yokoyama M: Involvement of NADH/NADPH oxidase in human platelet ROS production. Thromb. Res. 103:399-409, 2001. Go to original source... Go to PubMed...
  27. Tahri A, Yamani S, Legssyer A, Aziz M, Mekhfi H, Bnouham M, Ziyyat A: Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica. J. Ethnopharmacol. 73:95-100, 2000. Go to original source... Go to PubMed...
  28. Willoughby S, Holmes A, Loscalzo J: Platelets and cardiovascular disease. Eur. J. Cardiovasc. Nurs. 1:273-288, 2002. Go to original source... Go to PubMed...
  29. Ziyyat A, Legssyer A, Mekhfi H, Dassouli A, Serhrouchni M, Benjelloun W: Phytotherapy of hypertension and diabetes in oriental Morocco. J. Ethnopharmacol. 58:45-54, 1997. Go to original source... Go to PubMed...