Skip to main content
SpringerLink
Log in

Evaluation of the antiaggregant activity of ascorbyl phenolic esters with antioxidant properties

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Beneficial effects of the antioxidant L-ascorbic acid (Asc) in human health are well known. Its particular role in hemostasis deserves further consideration, since it has been described a dose-dependent effect of Asc in platelet activity. Contrary, it has been demonstrated that phenolic compounds have inhibitory effects on platelet aggregation stimulated by the physiological agonist thrombin (Thr). Here, we have evaluated the actions of three synthetic phenolic esters of Asc: L-ascorbyl 6-protocatechuate (Prot Asc), L-ascorbyl 6-gallate (Gal Asc), and L-ascorbyl 6-caffeate (Caf Asc). All these Asc derivatives exhibited greater radical scavenging activity than Asc, and in experiments using human platelets from healthy subjects, they do not evoke changes in platelet viability upon their administration. Nevertheless, these compounds altered platelet calcium homeostasis in response to Thr, although Prot Asc induced a smaller effect than Gal Asc, Caf Asc, and Asc. As a consequence, platelet aggregation was also impaired by these compounds, reporting Prot Asc and Caf Asc a weaker antiaggregant action than Gal Asc and Asc. Treatments with Gal Asc and Caf Asc altered in larger extent the phosphorylation pattern of pp60Src and mammalian target of rapamycin (mTOR) evoked by stimulating human platelets with Thr. Summarizing, Prot Asc is the ascorbyl phenolic ester with the strongest antioxidant properties and weakest antiaggregant actions, and its use as antioxidant may be safer than the rest of derivatives in order to prevent thrombotic alteration in patients that need treatment with antioxidant therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

[Ca2+]c :

Cytosolic free-calcium concentration

HBS:

HEPES-buffered saline

ROS:

Reactive oxygen species

Thr:

Thrombin

Asc:

L-ascorbic acid

Prot Asc:

L-ascorbyl 6-protocatechuate

Gal Asc:

L-ascorbyl 6-gallate

Caf Asc:

L-ascorbyl 6-caffeate

AA:

Arachidonic acid

PRP:

Platelet-rich plasma

DPPH• :

2,2-Diphenyl-1-picryhydrazyl radical

HPLC:

High-performance liquid chromatography

TMS:

Tetramethylsilane

J :

Coupling constants

s:

Singlet

d:

Doublet

dd:

Double doublet

ddd:

Double double doublet

m:

Multiplet

TLC:

Thin-layer chromatography

ARP:

Antiradical power

References

  1. Ahmad A, Khan RM, Alkharfy KM (2013) Effects of selected bioactive natural products on the vascular endothelium. J Cardiovasc Pharmacol 62:111–121

    Article  CAS  PubMed  Google Scholar 

  2. Alexandru N, Jardin I, Popov D, Simionescu M, Garcia-Estan J, Salido GM, Rosado JA (2008) Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus. J Cell Mol Med 12:2015–2026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Anwar J, Spanevello RM, Pimentel VC, Gutierres J, Thome G, Cardoso A, Zanini D, Martins C, Palma HE, Bagatini MD, Baldissarelli J, Schmatz R, Leal CA, Costa P, Morsch VM, Schetinger MR (2013) Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats. Food Chem Toxicol 56:459–466

    Article  CAS  PubMed  Google Scholar 

  4. Arya AK, Pokharia D, Tripathi K (2011) Relationship between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wound. Diabetes Res Clin Pract 94:377–384

    Article  CAS  PubMed  Google Scholar 

  5. Baguley BC, Ding Q, Richardson E (2014) Preliminary evidence that high-dose vitamin C has a vascular disrupting action in mice. Front Oncol 4:310

    Article  PubMed Central  PubMed  Google Scholar 

  6. Begonja AJ, Teichmann L, Geiger J, Gambaryan S, Walter U (2006) Platelet regulation by NO/cGMP signaling and NAD(P)H oxidase-generated ROS. Blood Cells Mol Dis 36:166–170

    Article  CAS  PubMed  Google Scholar 

  7. Bouaziz A, Salido S, Linares-Palomino PJ, Sanchez A, Altarejos J, Bartegi A, Salido GM, Rosado JA (2007) Cinnamtannin B-1 from bay wood reduces abnormal intracellular Ca2+ homeostasis and platelet hyperaggregability in type 2 diabetes mellitus patients. Arch Biochem Biophys 457:235–242

    Article  CAS  PubMed  Google Scholar 

  8. Braakhuis AJ (2012) Effect of vitamin C supplements on physical performance. Curr Sports Med Rep 11:180–184

    Article  PubMed  Google Scholar 

  9. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. Lebensm Wiss Technol 28:25–30

    Article  CAS  Google Scholar 

  10. Byshevskii A, Mataev SI, Rudzevich A, Shpovalova EM (2008) Hemostasis and maintenange of the organism vitamin C. Vopr Pitan 77:21–28

    CAS  PubMed  Google Scholar 

  11. Chang SS, Lee VS, Tseng YL, Chang KC, Chen KB, Chen YL, Li CY (2012) Gallic acid attenuates platelet activation and platelet-leukocyte aggregation: involving pathways of Akt and GSK3beta. Evid Based Complement Alternat Med 2012:683872

    PubMed Central  PubMed  Google Scholar 

  12. Chapado L, Linares-Palomino PJ, Salido S, Altarejos J, Rosado JA, Salido GM (2010) Synthesis and evaluation of the platelet antiaggregant properties of phenolic antioxidants structurally related to rosmarinic acid. Bioorg Chem 38:108–114

    Article  CAS  PubMed  Google Scholar 

  13. Chen S, Su Y, Wang J (2013) ROS-mediated platelet generation: a microenvironment-dependent manner for megakaryocyte proliferation, differentiation, and maturation. Cell Death Dis 4:e722

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Cordova C, Musca A, Violi F, Perrone A, Alessandri C (1982) Influence of ascorbic acid on platelet aggregation in vitro and in vivo. Atherosclerosis 41:15–19

    Article  CAS  PubMed  Google Scholar 

  15. Crescente M, Cerletti C, de Gaetano G (2007) Gallic acid, a dietary polyphenolic component, blunts the inhibition of platelet COX-1 by aspirin: preliminary in-vitro findings. Thromb Haemost 97:1054–1056

    CAS  PubMed  Google Scholar 

  16. Cumming KT, Raastad T, Holden G, Bastani NE, Schneeberger D, Paronetto MP, Mercatelli N, Ostgaard HN, Ugelstad I, Caporossi D, Blomhoff R, Paulsen G (2014) Effects of vitamin C and E supplementation on endogenous antioxidant systems and heat shock proteins in response to endurance training. Physiol Rep 2:e12142

    Article  PubMed Central  PubMed  Google Scholar 

  17. Dayal S, Wilson KM, Motto DG, Miller FJ Jr, Chauhan AK, Lentz SR (2013) Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis. Circulation 127:1308–1316

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Dey F, Moller A, Kemkes-Matthes B, Wilbrand JF, Krombach GA, Neubauer B, Hahn A (2012) Reduced platelet aggregation in a boy with scurvy. Klin Padiatr 224:448–452

    Article  CAS  PubMed  Google Scholar 

  19. Draeger CL, Naves A, Marques N, Baptistella AB, Carnauba RA, Paschoal V, Nicastro H (2014) Controversies of antioxidant vitamins supplementation in exercise: ergogenic or ergolytic effects in humans? J Int Soc Sports Nutr 11:4

    Article  PubMed Central  PubMed  Google Scholar 

  20. Feng W, Chang C, Luo D, Su H, Yu S, Hua W, Chen Z, Hu H, Liu W (2014) Dissection of autophagy in human platelets. Autophagy 10:642–651

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Frei B, Birlouez-Aragon I, Lykkesfeldt J (2012) Authors’ perspective: what is the optimum intake of vitamin C in humans? Crit Rev Food Sci Nutr 52:815–829

    Article  CAS  PubMed  Google Scholar 

  22. Frost RA, Pereyra E, Lang CH (2011) Ethyl pyruvate preserves IGF-I sensitivity toward mTOR substrates and protein synthesis in C2C12 myotubes. Endocrinology 152:151–163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Gan LaS PA (1998) Preparation and antioxidant activities of phenolic esters and ethers of L-ascorbic acid. J Carbohydr Chem 17:397–404

    Article  Google Scholar 

  24. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450

    CAS  PubMed  Google Scholar 

  25. Hajjar DP, Gotto AM Jr (2013) Biological relevance of inflammation and oxidative stress in the pathogenesis of arterial diseases. Am J Pathol 182:1474–1481

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Hathcock JN, Azzi A, Blumberg J, Bray T, Dickinson A, Frei B, Jialal I, Johnston CS, Kelly FJ, Kraemer K, Packer L, Parthasarathy S, Sies H, Traber MG (2005) Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr 81:736–745

    CAS  PubMed  Google Scholar 

  27. Hoshino Y, Yamada S, Saitoh S, Machii H, Mizukami H, Miyata M, Misaka T, Ishigami A, Takeishi Y (2013) Age-related oxidant stress with senescence marker protein-30 deficiency plays a pivotal role in coronary artery spasm. Coron Artery Dis 24:110–118

    Article  PubMed  Google Scholar 

  28. Hsiao G, Lee JJ, Lin KH, Shen CH, Fong TH, Chou DS, Sheu JR (2007) Characterization of a novel and potent collagen antagonist, caffeic acid phenethyl ester, in human platelets: in vitro and in vivo studies. Cardiovasc Res 75:782–792

    Article  CAS  PubMed  Google Scholar 

  29. Hung CC, Tsai WJ, Kuo LM, Kuo YH (2005) Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents. Bioorg Med Chem 13:1791–1797

    Article  CAS  PubMed  Google Scholar 

  30. Jiang B, Xiao S, Khan MA, Xue M (2013) Defective antioxidant systems in cervical cancer. Tumour Biol 34:2003–2009

    Article  CAS  PubMed  Google Scholar 

  31. Kang Z, Zhu H, Jiang W, Zhang S (2013) Protocatechuic acid induces angiogenesis through PI3K-Akt-eNOS-VEGF signalling pathway. Basic Clin Pharmacol Toxicol 113:221–227

    Article  CAS  PubMed  Google Scholar 

  32. Karakilcik AZ, Halat R, Zerin M, Celik H, Nazligul Y (2014) Effects of vitamin C and exercise on lipid profile, platelet and erythrocyte indices in young soccer players. J Sports Med Phys Fitness 54:665–671

    CAS  PubMed  Google Scholar 

  33. Kim K, Bae ON, Lim KM, Noh JY, Kang S, Chung KY, Chung JH (2012) Novel antiplatelet activity of protocatechuic acid through the inhibition of high shear stress-induced platelet aggregation. J Pharmacol Exp Ther 343:704–711

    Article  CAS  PubMed  Google Scholar 

  34. Kim KH, Barazia A, Cho J (2013) Real-time imaging of heterotypic platelet-neutrophil interactions on the activated endothelium during vascular inflammation and thrombus formation in live mice. J Vis Exp 74:e50329

  35. Kim SR, Jung YR, Kim DH, An HJ, Kim MK, Kim ND, Chung HY (2014) Caffeic acid regulates LPS-induced NF-kappaB activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells. Arch Pharm Res 37:539–547

    Article  CAS  PubMed  Google Scholar 

  36. Lee ES, Lee JO, Lee SK, Kim JH, Jung JH, Keum B, Park SH, Kim HS (2009) Caffeic acid phenethyl ester accumulates beta-catenin through GSK-3beta and participates in proliferation through mTOR in C2C12 cells. Life Sci 84:755–759

    Article  CAS  PubMed  Google Scholar 

  37. Lidington D, Ouellette Y, Li F, Tyml K (2003) Conducted vasoconstriction is reduced in a mouse model of sepsis. J Vasc Res 40:149–158

    Article  CAS  PubMed  Google Scholar 

  38. Lopez E, Berna-Erro A, Bermejo N, Brull JM, Martinez R, Garcia Pino G, Alvarado R, Salido GM, Rosado JA, Cubero JJ, Redondo PC (2013) Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients. J Cell Mol Med 17:636–647

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Lopez E, Berna-Erro A, Hernandez-Cruz JM, Salido GM, Redondo PC, Rosado JA (2013) Immunophilins are involved in the altered platelet aggregation observed in patients with type 2 diabetes mellitus. Curr Med Chem 20:1912–1921

    Article  CAS  PubMed  Google Scholar 

  40. Lopez E, Berna-Erro A, Salido GM, Rosado JA, Redondo PC (2013) FKBP52 is involved in the regulation of SOCE channels in the human platelets and MEG 01 cells. Biochim Biophys Acta 1833:652–662

    Article  CAS  PubMed  Google Scholar 

  41. Mathew MC, Ervin AM, Tao J, Davis RM (2012) Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. Cochrane Database Syst Rev 6:CD004567

    PubMed Central  PubMed  Google Scholar 

  42. McHugh GJ, Graber ML, Freebairn RC (2008) Fatal vitamin C-associated acute renal failure. Anaesth Intensive Care 36:585–588

    CAS  PubMed  Google Scholar 

  43. Moon CY, Ku CR, Cho YH, Lee EJ (2012) Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis. Biochem Biophys Res Commun 423:116–121

    Article  CAS  PubMed  Google Scholar 

  44. Moretti M, Budni J, Freitas AE, Rosa PB, Rodrigues AL (2014) Antidepressant-like effect of ascorbic acid is associated with the modulation of mammalian target of rapamycin pathway. J Psychiatr Res 48:16–24

    Article  PubMed  Google Scholar 

  45. Naseem KM, Chirico S, Mohammadi B, Bruckdorfer KR (1996) The synergism of hydrogen peroxide with plasma S-nitrosothiols in the inhibition of platelet activation. Biochem J 318:759–766

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Natella F, Nardini M, Belelli F, Pignatelli P, Di Santo S, Ghiselli A, Violi F, Scaccini C (2008) Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation. Br J Nutr 100:1276–1282

    Article  CAS  PubMed  Google Scholar 

  47. Niu H, Chen X, Gruppo RA, Li D, Wang Y, Zhang L, Wang K, Chai W, Sun Y, Ding Z, Gartner TK, Liu J (2012) Integrin alphaIIb-mediated PI3K/Akt activation in platelets. PLoS One 7:e47356

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Olas B, Hamed AI, Oleszek W, Stochmal A (2015) Comparison of biological activity of phenolic fraction from roots of Alhagi maurorum with properties of commercial phenolic extracts and resveratrol. Platelets 22:1–7

    Article  Google Scholar 

  49. Olas B, Wachowicz B (2002) Resveratrol and vitamin C as antioxidants in blood platelets. Thromb Res 106:143–148

    Article  CAS  PubMed  Google Scholar 

  50. Park JB (2009) 5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets. J Nutr Biochem 20:800–805

    Article  CAS  PubMed  Google Scholar 

  51. Paulsen G, Hamarsland H, Cumming KT, Johansen RE, Hulmi JJ, Borsheim E, Wiig H, Garthe I, Raastad T (2014) Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training. J Physiol 592:5391–5408

    Article  CAS  PubMed  Google Scholar 

  52. Pignatelli P, Sanguigni V, Paola SG, Lo Coco E, Lenti L, Violi F (2005) Vitamin C inhibits platelet expression of CD40 ligand. Free Radic Biol Med 38:1662–1666

    Article  CAS  PubMed  Google Scholar 

  53. Raghavan SA, Sharma P, Dikshit M (2003) Role of ascorbic acid in the modulation of inhibition of platelet aggregation by polymorphonuclear leukocytes. Thromb Res 110:117–126

    Article  CAS  PubMed  Google Scholar 

  54. Redondo PC, Ben-Amor N, Salido GM, Bartegi A, Pariente JA, Rosado JA (2005) Ca2+-independent activation of Bruton’s tyrosine kinase is required for store-mediated Ca2+ entry in human platelets. Cell Signal 17:1011–1021

    Article  CAS  PubMed  Google Scholar 

  55. Redondo PC, Harper MT, Rosado JA, Sage SO (2006) A role for cofilin in the activation of store-operated calcium entry by de novo conformational coupling in human platelets. Blood 107:973–979

    Article  CAS  PubMed  Google Scholar 

  56. Redondo PC, Jardin I, Hernandez-Cruz JM, Pariente JA, Salido GM, Rosado JA (2005) Hydrogen peroxide and peroxynitrite enhance Ca2+ mobilization and aggregation in platelets from type 2 diabetic patients. Biochem Biophys Res Commun 333:794–802

    Article  CAS  PubMed  Google Scholar 

  57. Redondo PC, Jardin I, Lopez JJ, Salido GM, Rosado JA (2008) Intracellular Ca2+ store depletion induces the formation of macromolecular complexes involving hTRPC1, hTRPC6, the type II IP3 receptor and SERCA3 in human platelets. Biochim Biophys Acta 1783:1163–1176

    Article  CAS  PubMed  Google Scholar 

  58. Redondo PC, Salido GM, Pariente JA, Rosado JA (2004) Dual effect of hydrogen peroxide on store-mediated calcium entry in human platelets. Biochem Pharmacol 67:1065–1076

    Article  CAS  PubMed  Google Scholar 

  59. Redondo PC, Salido GM, Rosado JA, Pariente JA (2004) Effect of hydrogen peroxide on Ca2+ mobilisation in human platelets through sulphydryl oxidation dependent and independent mechanisms. Biochem Pharmacol 67:491–502

    Article  CAS  PubMed  Google Scholar 

  60. Rosado JA, Graves D, Sage SO (2000) Tyrosine kinases activate store-mediated Ca2+ entry in human platelets through the reorganization of the actin cytoskeleton. Biochem J 351(Pt 2):429–437

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Rosado JA, Redondo PC, Salido GM, Gomez-Arteta E, Sage SO, Pariente JA (2004) 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

    Article  CAS  PubMed  Google Scholar 

  62. Rosado JA, Saavedra FR, Redondo PC, Hernandez-Cruz JM, Salido GM, Pariente JA (2004) Reduced plasma membrane Ca2+-ATPase function in platelets from patients with non-insulin-dependent diabetes mellitus. Haematologica 89:1142–1144

    CAS  PubMed  Google Scholar 

  63. Saavedra FR, Redondo PC, Hernandez-Cruz JM, Salido GM, Pariente JA, Rosado JA (2004) 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

    Article  CAS  PubMed  Google Scholar 

  64. Savini I, Catani MV, Arnone R, Rossi A, Frega G, Del Principe D, Avigliano L (2007) Translational control of the ascorbic acid transporter SVCT2 in human platelets. Free Radic Biol Med 42:608–616

    Article  CAS  PubMed  Google Scholar 

  65. Schindler TH, Lewandowski E, Olschewski M, Hasler K, Solzbach U, Just H (2002) Effect of vitamin C on platelet aggregation in smokers and nonsmokers. Med Klin (Munich) 97:263–269

    Article  CAS  Google Scholar 

  66. Sena LA, Chandel NS (2012) Physiological roles of mitochondrial reactive oxygen species. Mol Cell 48:158–167

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Sharma P, Raghavan SA, Dikshit M (2003) Role of ascorbate in the regulation of nitric oxide generation by polymorphonuclear leukocytes. Biochem Biophys Res Commun 309:12–17

    Article  CAS  PubMed  Google Scholar 

  68. Suzuki-Inoue K, Fuller GL, Garcia A, Eble JA, Pohlmann S, Inoue O, Gartner TK, Hughan SC, Pearce AC, Laing GD, Theakston RD, Schweighoffer E, Zitzmann N, Morita T, Tybulewicz VL, Ozaki Y, Watson SP (2006) A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107:542–549

    Article  CAS  PubMed  Google Scholar 

  69. Suzuki-Inoue K, Hughes CE, Inoue O, Kaneko M, Cuyun-Lira O, Takafuta T, Watson SP, Ozaki Y (2007) Involvement of Src kinases and PLCgamma2 in clot retraction. Thromb Res 120:251–258

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Tan HK, Moad AI, Tan ML (2014) The mTOR signalling pathway in cancer and the potential mTOR inhibitory activities of natural phytochemicals. Asian Pac J Cancer Prev 15:6463–6475

    Article  PubMed  Google Scholar 

  71. Tokiwa YaT F (2009) El método de síntesis y éster de ácido ascórbico. (Verde Products Laboratory Co., L., ed.)^eds.), Japan

  72. Toliopoulos IK, Simos YV, Daskalou TA, Verginadis II, Evangelou AM, Karkabounas SC (2011) Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid. Indian J Exp Biol 49:904–908

    CAS  PubMed  Google Scholar 

  73. Tsai WJ, Hsieh HT, Chen CC, Kuo YC, Chen CF (1998) Characterization of the antiplatelet effects of (2S)-5-methoxy-6-methylflavan-7-ol from Draconis Resina. Eur J Pharmacol 346:103–110

    Article  CAS  PubMed  Google Scholar 

  74. Tyml K (2011) Critical role for oxidative stress, platelets, and coagulation in capillary blood flow impairment in sepsis. Microcirculation 18:152–162

    Article  CAS  PubMed  Google Scholar 

  75. Vericel E, Colas R, Calzada C, Le QH, Feugier N, Cugnet C, Vidal H, Laville M, Moulin P, Lagarde M (2015) Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients. Thromb Haemost. doi:10.1160/TH14-12-1003

    PubMed  Google Scholar 

  76. Weyrich AS, Denis MM, Schwertz H, Tolley ND, Foulks J, Spencer E, Kraiss LW, Albertine KH, McIntyre TM, Zimmerman GA (2007) mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Blood 109:1975–1983

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Wilkinson IB, Megson IL, MacCallum H, Sogo N, Cockcroft JR, Webb DJ (1999) Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol 34:690–693

    Article  CAS  PubMed  Google Scholar 

  78. Williams MH (1984) Vitamin and mineral supplements to athletes: do they help? Clin Sports Med 3:623–637

    CAS  PubMed  Google Scholar 

  79. Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP (2014) Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac J Clin Oncol 10:22–37

    Article  PubMed  Google Scholar 

  80. Xiao H, Kovics R, Jackson V, Remick DG (2004) Effects of platelet inhibitors on propyl gallate-induced platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activation. Blood Coagul Fibrinolysis 15:199–206

    Article  CAS  PubMed  Google Scholar 

  81. Yin K, Lai PS, Rodriguez A, Spur BW, Wong PY (1995) Antithrombotic effects of peroxynitrite: inhibition and reversal of aggregation in human platelets. Prostaglandins 50:169–178

    Article  CAS  PubMed  Google Scholar 

  82. Zbidi H, Salido S, Altarejos J, Perez-Bonilla M, Bartegi A, Rosado JA, Salido GM (2009) Olive tree wood phenolic compounds with human platelet antiaggregant properties. Blood Cells Mol Dis 42:279–285

    Article  CAS  PubMed  Google Scholar 

  83. Zhou-Stache J, Buettner R, Artmann G, Mittermayer C, Bosserhoff AK (2002) Inhibition of TNF-alpha induced cell death in human umbilical vein endothelial cells and Jurkat cells by protocatechuic acid. Med Biol Eng Comput 40:698–703

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by MEC (BFU2013-45564C2-1-P), Junta de Extremadura-FEDER (PRIBS10020), and University of Jaen Research Program (UJA-08-16-05). Esther Lopez is supported by NIH Carlos III Health Program (FI10/00573).

Author information

Authors and Affiliations

  1. Department of Physiology, University of Extremadura, Av. Universidad s/n, 10003, Cáceres, Spain

    Esther Lopez, Ginés M. Salido, Juan A. Rosado & Pedro C. Redondo

  2. Department of Inorganic and Organic Chemistry, University of Jaen, 23071, Jaen, Spain

    María del Carmen Ortega-Liébana, Sofía Salido & Joaquín Altarejos

Authors
  1. Esther Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María del Carmen Ortega-Liébana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sofía Salido
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ginés M. Salido
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joaquín Altarejos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juan A. Rosado
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pedro C. Redondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pedro C. Redondo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopez, E., del Carmen Ortega-Liébana, M., Salido, S. et al. Evaluation of the antiaggregant activity of ascorbyl phenolic esters with antioxidant properties. J Physiol Biochem 71, 415–434 (2015). https://doi.org/10.1007/s13105-015-0421-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-015-0421-0

Keywords

Search

Navigation