SUMMARY
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.
KEY WORDS
platelets; type 2 diabetes mellitus; Urtica dioica; calcium mobilization; antioxidant; tyrosine phosphorylation
REFERENCES
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.
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.
Blankenship KA, Dawson CB, Aronoff GR, Dean
WL: Tyrosine phosphorylation of human
platelet plasma membrane Ca2+-ATPase in
hypertension. Hypertension 35:103-107, 2000.
Blann AD, Nadar S, Lip GY: Pharmacological
modulation of platelet function in
hypertension. Hypertension 42:1-7, 2003.
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.
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.
Dogne JM, Leval XD, Benoit P, Delarge J,
Masereel B, David JL: Recent advances in
antiplatelet agents. Curr Med Chem 9:577-589, 2002.
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.
Garnier G, Bezanger-Beauquesne L, Debraux G:
Ressources medicinales de la flore francaise,
Vol 2, Vigot Freres, Paris 1961, pp. 962-964.
Grynkiewicz G, Poenie M, Tsien RY: A new
generation of Ca2+ indicators with greatly
improved fluorescence properties. J Biol
Chem 260:3440-3450, 1985.
Jardin 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.
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.
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.
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.
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.
Pignatelli P, Pulcinelli FM, Lenti L, Gazzaniga PP,
Violi F: Hydrogen peroxide is involved in
collagen-induced platelet activation. Blood 91:484-490, 1998.
Redondo PC, Jardin 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.
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.
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.
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.
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.
Rosado JA, Saavedra FR, Redondo PC, Hernandez-
Cruz JM, Salido GM, Pariente JA: Reduced
plasma membrane Ca2+-ATPase function in
platelets from patients with non-insulindependent
diabetes mellitus. Haematologica
89:1142-1144, 2004c.
Rosado JA, Sage SO: The actin cytoskeleton in
store-mediated calcium entry. J Physiol 526:221-229, 2000.
Ruf JC: Alcohol, wine and platelet function. Biol
Res 37:209-215, 2004.
Saavedra FR, Redondo PC, Hernandez-Cruz JM,
Salido GM, Pariente JA, Rosado JA: Storeoperated
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.
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.
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.
Willoughby S, Holmes A, Loscalzo J: Platelets and
cardiovascular disease. Eur J Cardiovasc
Nurs 1:273-288 , 2002.
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.
|
CITED
Sujatha S, Jemima Shalin J. Complementary therapeutic potential: A focus on polyherbal products for hyperglycemia. Asian J Sci Res. 5: 1-13, 2012.
Mehri A, Hasani-Ranjbar S, Larijani B, Abdollahi MA. systematic review of efficacy and safety of urtica dioica in the treatment of diabetes. Int J Pharm. 7: 161-170, 2011.
El Haouari M, Rosado JA. Modulation of Platelet Function and Signaling by Flavonoids. Mini-Rev Med Chem. 11: 131-142, 2011.
El Haouari M, Rosado JA. Platelet signalling abnormalities in patients with type 2 diabetes mellitus: A review. Blood Cells Mol Dis. 41: 119-123, 2008.
Lopez JJ, Jardin I, Salido GM, Rosado JA. Cinnamtannin B-1 as an antioxidant and platelet aggregation inhibitor. Life Sci. 82: 977-982, 2008.
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