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Cardiovascular & Hematological Agents in Medicinal Chemistry


ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Mini-Review Article

The Platelet Aggregation Inhibition Activity of Polyphenols can be Mediated by 67kda Laminin Receptor: A New Therapeutic Strategy For the Treatment of Venous Thromboembolism

Author(s): Satya Prakash, Amit Ghosh*, Arnab Nayek and Sheetal Kiran

Volume 22, Issue 1, 2024

Published on: 02 May, 2023

Page: [1 - 6] Pages: 6

DOI: 10.2174/1871525721666230228120500

Price: $65


Background: Thrombotic disease is still a major killer. Aspirin, Ticagrelor, Clopidogrel, etc. are the most widely used conventional antiplatelet drugs. The significant number of patients who are resistant to this drug shows a poor outcome.

Objective: Developing a new antiplatelet agent with a stable antiplatelet effect and minimal bleeding risk is required for a patient who is resistant to antiplatelet drugs.

Methods: Protein-ligand docking was performed using Autodock Vina 1.1.2 to study the interaction of 67LR with different Polyphenols.

Results: Among the 18 polyphenols, thearubigin has the highest binding affinity towards 67LR and gallic acid shows the lowest binding affinity. Among the 18 molecules, the top 4 molecules from the highest to lowest binding affinity range from-10.6 (thearubigin) to -6.5 (Epigallocatechin).

Conclusion: Polyphenols may inhibit platelet aggregation through 67 LR and can be an alternative treatment for Thrombotic Disease. Moreover, it will be interesting to know whether polyphenols interfere with the same pathways as aspirin and clopidogrel. Effective polyphenols could help prototype the compound development of novel antiplatelet agents.

Keywords: Laminin receptor, epigallocatechin gallate, EGCG, epigallocatechin, antiplatelet, polyphenols, flavonoids.

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Lüscher, T.F.; Noll, G. The pathogenesis of cardiovascular disease: Role of the endothelium as a target and mediator. Atherosclerosis, 1995, 118(Suppl.), S81-S90.
[] [PMID: 8821468]
Li, J; Song, M; Jian, Z; Guo, W; Chen, G; Jiang, G; Wang, J; Wu, X; Huang, L . Laboratory aspirin resistance and the risk of major adverse cardiovascular events in patients with coronary heart disease on confirmed aspirin adherence. J Atheroscler Thromb. 2014, 21(3), 239-47. Epub 2013 Nov 7.
[] [PMID: 24201035]
Müller, I.; Besta, F.; Schulz, C.; Massberg, S.; Schönig, A.; Gawaz, M. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb. Haemost., 2003, 89(5), 783-787.
[] [PMID: 12719773]
Lev, E.I.; Patel, R.T.; Maresh, K.J.; Guthikonda, S.; Granada, J.; DeLao, T.; Bray, P.F.; Kleiman, N.S. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: The role of dual drug resistance. J. Am. Coll. Cardiol., 2006, 47(1), 27-33.
[] [PMID: 16386660]
Cuisset, T.; Frere, C.; Quilici, J.; Uhry, S.; Alessi, M.C.; Bonnet, J.L. Post-PCI fatal bleeding in aspirin and clopidogrel hyper responder. Int. J. Cardiol., 2010, 138(2), 212-213.
[] [PMID: 18707772]
Yeung, J.; Holinstat, M. 12-lipoxygenase: A potential target for novel anti-platelet therapeutics. Cardiovasc. Hematol. Agents Med. Chem., 2011, 9(3), 154-164.
[] [PMID: 21838667]
McCullough, M.L.; Peterson, J.J.; Patel, R.; Jacques, P.F.; Shah, R.; Dwyer, J.T. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am. J. Clin. Nutr., 2012, 95(2), 454-464.
[] [PMID: 22218162]
Geleijnse, J.M.; Launer, L.J.; van der Kuip, D.A.M.; Hofman, A.; Witteman, J.C.M. Inverse association of tea and flavonoid intakes with incident myocardial infarction: The Rotterdam Study. Am. J. Clin. Nutr., 2002, 75(5), 880-886.
[] [PMID: 11976162]
Engler, M.B.; Engler, M.M. The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease. Nutr. Rev., 2006, 64(3), 109-118.
[] [PMID: 16572598]
Beretz, A.; Cazenave, J.P.; Anton, R. Inhibition of aggregation and secretion of human platelets by quercetin and other flavonoids: Structure-activity relationships. Agents Actions, 1982, 12(3), 382-387.
[] [PMID: 6182778]
Pietta, P.G. Flavonoids as antioxidants. J. Nat. Prod., 2000, 63(7), 1035-1042.
[] [PMID: 10924197]
Rechner, A.R.; Kroner, C. Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thromb. Res., 2005, 116(4), 327-334.
[ ] [PMID: 16038718]
Hubbard, G.P.; Wolffram, S.; Lovegrove, J.A.; Gibbins, J.M. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen‐stimulated platelet activation pathway in humans. J. Thromb. Haemost., 2004, 2(12), 2138-2145.
[] [PMID: 15613018]
Vitseva, O.; Varghese, S.; Chakrabarti, S.; Folts, J.D.; Freedman, J.E. Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. J. Cardiovasc. Pharmacol., 2005, 46(4), 445-451.
[] [PMID: 16160595]
Freedman, J.E.; Parker, C., III; Li, L.; Perlman, J.A.; Frei, B.; Ivanov, V.; Deak, L.R.; Iafrati, M.D.; Folts, J.D. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation, 2001, 103(23), 2792-2798.
[] [PMID: 11401934]
Walter, U.; Eigenthaler, M.; Geiger, J.; Reinhard, M. Role of cyclic nucleotide-dependent protein kinases and their common substrate VASP in the regulation of human platelets. Adv. Exp. Med. Biol., 1993, 344, 237-249.
[] [PMID: 8209791]
Sheu, J.R.; Hsiao, G.; Chou, P.H.; Shen, M.Y.; Chou, D.S. Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets. J. Agric. Food Chem., 2004, 52(14), 4414-4418.
[] [PMID: 15237945]
Chen, W.M.; Jin, M.; Wu, W. Experimental study on inhibitory effect of Rutin against platelet activation induced by platelet activating factor in rabbits. Chin. J. Integr. Trad. Western Med., 2002, 22(4), 283-285.
[PMID: 12584792]
Chen, X.Q.; Wang, X.B.; Guan, R.F.; Tu, J.; Gong, Z.H.; Zheng, N.; Yang, J.H.; Zhang, Y.Y.; Ying, M.M. Blood anticoagulation and antiplatelet activity of green tea (−)-epigallocatechin (EGC) in mice. Food Funct., 2013, 4(10), 1521-1525.
[] [PMID: 24056410]
Kang, W.S.; Lim, I.H.; Yuk, D.Y.; Chung, K.H.; Park, J.B.; Yoo, H.S.; Yun, Y.P. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb. Res., 1999, 96(3), 229-237.
[] [PMID: 10588466]
Millington-Burgess, S.L.; Harper, M.T. Epigallocatechin gallate inhibits release of extracellular vesicles from platelets without inhibiting phosphatidylserine exposure. Sci. Rep., 2021, 11(1), 17678.
[] [PMID: 34480042]
Tachibana, H.; Koga, K.; Fujimura, Y.; Yamada, K. A receptor for green tea polyphenol EGCG. Nat. Struct. Mol. Biol., 2004, 11(4), 380-381.
[] [PMID: 15024383]
Jamieson, K.V.; Wu, J.; Hubbard, S.R.; Meruelo, D. Crystal structure of the human laminin receptor precursor. J. Biol. Chem., 2008, 283(6), 3002-3005.
[] [PMID: 18063583]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2009, 31(2)
[] [PMID: 19499576]
Tian, W.; Chen, C.; Lei, X.; Zhao, J.; Liang, J. CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res., 2018, 46(W1), W363-W367.
[] [PMID: 29860391]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19(14), 1639-1662.
Tandon, N.N.; Holland, E.A.; Kralisz, U.; Kleinman, HK.; Robey, FA.; Jamieson, GA. Interaction of human platelets with laminin and identification of the 67 kDa laminin receptor on platelets. Biochem. J., 1991, 274(2), 535-542.
Watson, S. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis. Curr. Pharm. Des., 2009, 15(12), 1358-1372.
[] [PMID: 19355974]
Schaff, M.; Tang, C.; Maurer, E.; Bourdon, C.; Receveur, N.; Eckly, A.; Hechler, B.; Arnold, C.; de Arcangelis, A.; Nieswandt, B.; Denis, C.V.; Lefebvre, O.; Georges-Labouesse, E.; Gachet, C.; Lanza, F.; Mangin, P.H. Integrin α6β1 is the main receptor for vascular laminins and plays a role in platelet adhesion, activation, and arterial thrombosis. Circulation, 2013, 128(5), 541-552.
[] [PMID: 23797810]
Chan, C.Y.; Wei, L.; Castro-Muñozledo, F.; Koo, W.L. (−)-Epigallocatechin-3-gallate blocks 3T3-L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression. Life Sci., 2011, 89(21-22), 779-785.
[] [PMID: 21978785]
Kim, J.E.; Park, H.; Lee, J.E.; Kang, T.C. Blockade of 67-kDa Laminin receptor facilitates AQP4 down-regulation and BBB disruption via ERK1/2-and p38 MAPK-Mediated PI3K/AKT activations. Cells, 2020, 9(7), 1670.
[] [PMID: 32664509]
Bao, S.; Cao, Y.; Zhou, H.; Sun, X.; Shan, Z.; Teng, W. Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes. J. Agric. Food Chem., 2015, 63(10), 2811-2819.
[] [PMID: 25732404]
Fujimura, Y.; Sumida, M.; Sugihara, K.; Tsukamoto, S.; Yamada, K.; Tachibana, H. Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. PLoS One, 2012, 7(5), e37942.
[] [PMID: 22666419]
Freedman, J.E.; Loscalzo, J.; Barnard, M.R.; Alpert, C.; Keaney, J.F.; Michelson, A.D. Nitric oxide released from activated platelets inhibits platelet recruitment. J. Clin. Invest., 1997, 100(2), 350-356.
[] [PMID: 9218511]
Nardini, M.; Natella, F.; Scaccini, C. Role of dietary polyphenols in platelet aggregation. A review of the supplementation studies. Platelets, 2007, 18(3), 224-243.
[] [PMID: 17497435]
Ostertag, L.M.; O’Kennedy, N.; Kroon, P.A.; Duthie, G.G.; de Roos, B. Impact of dietary polyphenols on human platelet function - A critical review of controlled dietary intervention studies. Mol. Nutr. Food Res., 2010, 54(1), 60-81.
[] [PMID: 20058256]
Mizukami, H.; Tomita, K.; Ohashi, H.; Hiraoka, N. Anthocyanin production in callus cultures of roselle (Hibiscus sabdariffa L.). Plant Cell Rep., 1988, 7(7), 553-556.
[] [PMID: 24240415]
Lu, Y.; Li, Q.; Liu, Y.Y.; Sun, K.; Fan, J.Y.; Wang, C.S.; Han, J.Y. Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogen-activated protein kinases. Sci. Rep., 2015, 5(1), 13824.
[] [PMID: 26345207]
Hung, C.C.; Tsai, W.J.; Kuo, L.M.Y.; Kuo, Y.H. Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents. Bioorg. Med. Chem., 2005, 13(5), 1791-1797.
[] [PMID: 15698796]
Fuentes, E.; Caballero, J.; Alarcón, M.; Rojas, A.; Palomo, I. Chlorogenic acid inhibits human platelet activation and thrombus formation. PLoS One, 2014, 9(3), e90699.
[] [PMID: 24598787]
Cho, H.J.; Kang, H.J.; Kim, Y.J.; Lee, D.H.; Kwon, H.W.; Kim, Y.Y.; Park, H.J. Inhibition of platelet aggregation by chlorogenic acid via cAMP and cGMP-dependent manner. Blood Coagul. Fibrinolysis, 2012, 23(7), 629-635.
[] [PMID: 22885765]
McNicol, A. The effects of genistein on platelet function are due to thromboxane receptor antagonism rather than inhibition of tyrosine kinase. Prostaglandins Leukot. Essent. Fatty Acids, 1993, 48(5), 379-384.
[] [PMID: 8321874]
Gottstein, N.; Ewins, B.A.; Eccleston, C.; Hubbard, G.P.; Kavanagh, I.C.; Minihane, A.M.; Weinberg, P.D.; Rimbach, G. Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function. Br. J. Nutr., 2003, 89(5), 607-615.
[] [PMID: 12720581]
Oh, W.J.; Endale, M.; Park, S.C.; Cho, J.Y.; Rhee, M.H. Dual Roles of Quercetin in Platelets: Phosphoinositide-3-Kinase and MAP Kinases Inhibition, and cAMP-Dependent Vasodilator-Stimulated Phosphoprotein Stimulation. Evid. Based Complement. Alternat. Med., 2012, 1-10.
[] [PMID: 23304202]
Ed Nignpense, B.; Chinkwo, K.A.; Blanchard, C.L.; Santhakumar, A.B. Polyphenols: Modulators of platelet function and platelet microparticle generation? Int. J. Mol. Sci., 2019, 21(1), 146.
[] [PMID: 31878290]
Inoue, O.; Suzuki-Inoue, K.; McCarty, O.J.T.; Moroi, M.; Ruggeri, Z.M.; Kunicki, T.J.; Ozaki, Y.; Watson, S.P. Laminin stimulates spreading of platelets through integrin α6β1–dependent activation of GPVI. Blood, 2006, 107(4), 1405-1412.
[] [PMID: 16219796]

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