Anti-platelet aggregation effects of extracts from Arbutus unedo leaves

Authors

  • Mohammed El Haouari Centre Régional des Métiers de l’Education et de la Formation de Taza (CRMEF – Taza), BP 1178 - Taza Gare
  • Hassane Mekhfi Laboratoire de Physiologie et Ethnopharmacologie, Département de biologie, Faculté des Sciences, Université Mohamed Premier, BP 717, 60000 Oujda

DOI:

https://doi.org/10.14719/pst.2017.4.2.298

Keywords:

Platelets, Aggregation, Arbutus unedo, Cardiovascular disease, Flavonoids, Rat

Abstract

It is well known that platelet hyperactivity is a risk factor for cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. This study aimed to examine the effects of extracts enriched in flavonoids obtained from Arbutus unedo leaves on platelet aggregation. Rat platelets were prepared and incubated in vitro with different doses of the tested extracts, and aggregation was trigged by physiological agonists. Platelet treatment with increasing concentrations (0.1 - 1 mg/ml) of diethyl ether extract (genins = free flavonoids) or ethyl acetate extract (hetrosidic flavonoids) inhibited platelet aggregation evoked by thrombin in a concentration-dependant manner. The IC50 values were 0.22 ± 0.03 and 0.36 ± 0.05 mg/ml for genins and heterosidic flavonoids respectively. Treatment with Arbutus unedo extracts also significantly reduced the initial rate of platelet aggregation. At 1 mg/ml, the rate inhibition was 97.8 ± 0.74 and 90.8 ± 1.55 % for genins and heterosidic flavonoids respectively. In addition, flavonoids significantly inhibited platelet aggregation induced by ADP, collagen or epinephrine. We conclude that Arbutus unedo extracts show antiaggregant effects due mainly to flavonoids. These results may partly explain the traditional use of Arbutus unedo leaves for the treatment of cardiovascular disorders such as hypertension.

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References

Bnouham, M., F. Z. Merhfour, A. Legssyer, H. Mekhfi, S. Maallem, and A. Ziyyat. 2007. Antihyperglycemic activity of Arbutus unedo, Ammoides pusilla and Thymelaea hirsuta. Pharmazie 62: 630-632

Delgado-Pelayo, R., L. Gallardo-Guerrero, and D. Hornero-Mendez. 2016. Carotenoid composition of strawberry tree (Arbutus unedo L.) fruits. Food Chem 199: 165-175. https://doi.org/10.1016/j.foodchem.2015.11.135

Dogne, J. M., X. de Leval, P. Benoit, J. Delarge, B. Masereel, and J. L. David. 2002. Recent advances in antiplatelet agents. Curr Med Chem 9: 577-589. https://doi.org/10.2174/0929867024606948

El Haouari, M., and J. A. Rosado. 2011. Modulation of platelet function and signaling by flavonoids. Mini Rev Med Chem 11: 131-142

El Haouari, M., and J. A. Rosado. 2016. Medicinal Plants with Antiplatelet Activity. Phytother Res 30: 1059-1071. https://doi.org/10.1002/ptr.5619

El Haouari, M., M. Bnouham, M. Bendahou, M. Aziz, A. Ziyyat, A. Legssyer, and H. Mekhfi. 2006. Inhibition of rat platelet aggregation by Urtica dioica leaves extracts. Phytother Res 20: 568-572. https://doi.org/10.2174/138955711794519537

Formica, J. V., and W. Regelson. 1995. Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol 33: 1061-1080. https://doi.org/10.1016/0278-6915(95)00077-1

Freedman, J. E., C. Parker, 3rd, L. Li, J. A. Perlman, B. Frei, V. Ivanov, L. R. Deak, M. D. Iafrati, and J. D. Folts. 2001. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 103: 2792-2798. https://doi.org/10.1161/01.CIR.103.23.2792

Ghayur, M. N., S. F. Kazim, H. Rasheed, A. Khalid, M. I. Jumani, M. I. Choudhary, and A. H. Gilani. 2011. Identification of antiplatelet and acetylcholinesterase inhibitory constituents in betel nut. Zhong Xi Yi Jie He Xue Bao 9: 619-625. https://doi.org/10.3736/jcim20110607

Heemskerk, J. W., and S. O. Sage. 1994. Calcium signalling in platelets and other cells. Platelets 5: 295-316. https://doi.org/10.3109/09537109409006439

Izzo, A. A., S. Hoon-Kim, R. Radhakrishnan, and E. M. Williamson. 2016. A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies. Phytother Res 30: 691-700. https://doi.org/10.1002/ptr.5591

Kang, W. S., I. H. Lim, D. Y. Yuk, K. H. Chung, J. B. Park, H. S. Yoo, and Y. P. Yun. 1999. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb Res 96: 229-237. https://doi.org/10.1016/S0049-3848(99)00104-8

Kang, W. S., K. H. Chung, J. H. Chung, J. Y. Lee, J. B. Park, Y. H. Zhang, H. S. Yoo, and Y. P. Yun. 2001. Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase. J Cardiovasc Pharmacol 38: 875-884. https://doi.org/10.1097/00005344-200112000-00009

Kelly, C., K. Hunter, L. Crosbie, M. J. Gordon, and A. K. Dutta-Roy. 1996. Modulation of human platelet function by food flavonoids. Biochem Soc Trans 24: 197S. https://doi.org/10.1042/bst024197s

Legssyer, A., A. Ziyyat, H. Mekh, M. Bnouham, C. Herrenknecht, V. Roumy, C. Fourneau, A. Laurens, J. Hoerter, and R. Fischmeister. 2004. Tannins and catechin gallate mediate the vasorelaxant effect of Arbutus unedo on the rat isolated aorta. Phytother Res 18: 889-894. https://doi.org/10.1002/ptr.1513

Liang, M. L., X. W. Da, A. D. He, G. Q. Yao, W. Xie, G. Liu, J. Z. Xiang, and Z. Y. Ming. 2015. Pentamethylquercetin (PMQ) reduces thrombus formation by inhibiting platelet function. Sci Rep 5: 11142. https://doi.org/10.1038/srep11142

Loomis, T.A., A.W. Hayes. Loomis’s Essentials of Toxicology, 4th ed. California: Academic Press; 1996: 208-245.

Lorke, D. 1983. A new approach to practical acute toxicity testing. Arch Toxicol 54: 275-287. https://doi.org/10.1007/BF01234480

Lu, W. J., K. C. Lin, C. P. Liu, C. Y. Lin, H. C. Wu, D. S. Chou, P. Geraldine, S. Y. Huang, C. Y. Hsieh, and J. R. Sheu. 2016. Prevention of arterial thrombosis by nobiletin: in vitro and in vivo studies. J Nutr Biochem 28: 1-8. https://doi.org/10.1016/j.jnutbio.2015.09.024

Males, Z., M. Plazibat, V. B. Vundac, and I. Zuntar. 2006. Qualitative and quantitative analysis of flavonoids of the strawberry tree - Arbutus unedo L. (Ericaceae). Acta Pharm 56: 245-250

Mariotto, S., E. Esposito, R. Di Paola, A. Ciampa, E. Mazzon, A. C. de Prati, E. Darra, S. Vincenzi, G. Cucinotta, R. Caminiti, H. Suzuki, and S. Cuzzocrea. 2008. Protective effect of Arbutus unedo aqueous extract in carrageenan-induced lung inflammation in mice. Pharmacol Res 57: 110-124. https://doi.org/10.1016/j.phrs.2007.12.005

Middleton, E. 1984. The flavonoids. Trends Pharm Science 5: 335-338.

Mekhfi, H., M. El Haouari, A. Legssyer, M. Bnouham, M. Aziz, F. Atmani, A. Remmal, and A. Ziyyat. 2004. Platelet anti-aggregant property of some Moroccan medicinal plants. J Ethnopharmacol 94: 317-322. https://doi.org/10.1016/j.jep.2004.06.005

Mekhfi, H., M. ElHaouari, M. Bnouham, M. Aziz, A. Ziyyat, and A. Legssyer. 2006. Effects of extracts and tannins from Arbutus unedo leaves on rat platelet aggregation. Phytother Res 20: 135-139. https://doi.org/10.1002/ptr.1822

Miguel, M. G., M. L. Faleiro, A. C. Guerreiro, and M. D. Antunes. 2014. Arbutus unedo L.: chemical and biological properties. Molecules 19: 15799-15823. https://doi.org/10.3390/molecules191015799

Oliveira, I., V. Coelho, R. Baltasar, J. A. Pereira, and P. Baptista. 2009. Scavenging capacity of strawberry tree (Arbutus unedo L.) leaves on free radicals. Food Chem Toxicol 47: 1507-1511. https://doi.org/10.1016/j.fct.2009.03.042

Pabuccuoglu, A., B. Kivcak, M. Bas, and T. Mert. 2003. Antioxidant activity of Arbutus unedo leaves. Fitoterapia 74: 597-599. https://doi.org/10.1016/S0367-326X(03)00110-2

Pearson, D. A., T. G. Paglieroni, D. Rein, T. Wun, D. D. Schramm, J. F. Wang, R. R. Holt, R. Gosselin, H. H. Schmitz, and C. L. Keen. 2002. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res 106: 191-197. https://doi.org/10.1016/S0049-3848(02)00128-7

Rein, D., T. G. Paglieroni, D. A. Pearson, T. Wun, H. H. Schmitz, R. Gosselin, and C. L. Keen. 2000a. Cocoa and wine polyphenols modulate platelet activation and function. J Nutr 130: 2120S-2126S

Rein, D., T. G. Paglieroni, T. Wun, D. A. Pearson, H. H. Schmitz, R. Gosselin, and C. L. Keen. 2000b. Cocoa inhibits platelet activation and function. Am J Clin Nutr 72: 30-35

Ro, J. Y., J. H. Ryu, H. J. Park, and H. J. Cho. 2015. Onion (Allium cepa L.) peel extract has anti-platelet effects in rat platelets. Springerplus 4: 17. https://doi.org/10.1186/s40064-015-0786-0

Rosado, J. A., J. J. Lopez, A. G. Harper, M. T. Harper, P. C. Redondo, J. A. Pariente, S. O. Sage, and G. M. Salido. 2004. Two pathways for store-mediated calcium entry differentially dependent on the actin cytoskeleton in human platelets. J Biol Chem 279: 29231-29235. https://doi.org/10.1074/jbc.M403509200

Son, D. J., M. R. Cho, Y. R. Jin, S. Y. Kim, Y. H. Park, S. H. Lee, S. Akiba, T. Sato, and Y. P. Yun. 2004. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids 71: 25-31. https://doi.org/10.1016/j.plefa.2003.12.004

Tomita, T., K. Umegaki, and E. Hayashi. 1983. Basic aggregation properties of washed rat platelets: correlation between aggregation, phospholipid degradation, malondialdehyde, and thromboxane formation. J Pharmacol Methods 10: 31-44. https://doi.org/10.1016/0160-5402(83)90012-8

Van De Graaff, E., and S. R. Steinhubl. 2001. Complications of oral antiplatelet medications. Curr Cardiol Rep 3: 371-379. https://doi.org/10.1007/s11886-001-0053-6

Wong, Y. W., R. Prakash, and D. P. Chew. 2010. Antiplatelet therapy in percutaneous coronary intervention: recent advances in oral antiplatelet agents. Curr Opin Cardiol 25: 305-311. https://doi.org/10.1097/HCO.0b013e328339f1aa

Ziyyat, A., A. Legssyer, H. Mekhfi, A. Dassouli, M. Serhrouchni, and W. Benjelloun. 1997. Phytotherapy of hypertension and diabetes in oriental Morocco. J Ethnopharmacol 58: 45-54. https://doi.org/10.1016/S0378-8741(97)00077-9

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Published

06-05-2017

How to Cite

1.
El Haouari M, Mekhfi H. Anti-platelet aggregation effects of extracts from Arbutus unedo leaves. Plant Sci. Today [Internet]. 2017 May 6 [cited 2024 Apr. 19];4(2):68-74. Available from: https://horizonepublishing.com/journals/index.php/PST/article/view/298

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