Cardiovascular Effects of Flavonoids

Manuel        Sánchez; Miguel        Romero; Manuel        Gómez-Guzmán; Juan        Tamargo; Francisco        Pérez-Vizcaino; Juan        Duarte
doi:10.2174/0929867326666181220094721
Abstract

Cardiovascular Disease (CVD) is the major cause of death worldwide, especially in Western society. Flavonoids are a large group of polyphenolic compounds widely distributed in plants, present in a considerable amount in fruit and vegetable. Several epidemiological studies found an inverse association between flavonoids intake and mortality by CVD. The antioxidant effect of flavonoids was considered the main mechanism of action of flavonoids and other polyphenols. In recent years, the role of modulation of signaling pathways by direct interaction of flavonoids with multiple protein targets, namely kinases, has been increasingly recognized and involved in their cardiovascular protective effect. There are strong evidence, in in vitro and animal experimental models, that some flavonoids induce vasodilator effects, improve endothelial dysfunction and insulin resistance, exert platelet antiaggregant and atheroprotective effects, and reduce blood pressure. Despite interacting with multiple targets, flavonoids are surprisingly safe. This article reviews the recent evidence about cardiovascular effects that support a beneficial role of flavonoids on CVD and the potential molecular targets involved.
Keywords: Flavonoids, endothelial function, hypertension, platelet aggregation, atherosclerosis, insulin resistance, myocardial ischemia, stroke.
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[1] 
Ververidis, F.; Trantas, E.; Douglas, C.; Vollmer, G.; Kretzschmar, G.; Panopoulos, N. Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnol. J.,  2007, 2(10), 1214-1234.
[http://dx.doi.org/10.1002/biot.200700084] [PMID:  17935117] 
[2] 
Middleton, E., Jr; Kandaswami, C.; Theoharides, T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev.,  2000, 52(4), 673-751.
[PMID:  11121513] 
[3] 
Williams, R.J.; Spencer, J.P.; Rice-Evans, C. Flavonoids: antioxidants or signalling molecules? Free Radic. Biol. Med.,  2004, 36(7), 838-849.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.01.001] [PMID:  15019969] 
[4] 
Yao, P.; Nussler, A.; Liu, L.; Hao, L.; Song, F.; Schirmeier, A.; Nussler, N. Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways. J. Hepatol.,  2007, 47(2), 253-261.
[http://dx.doi.org/10.1016/j.jhep.2007.02.008] [PMID:  17433488] 
[5] 
Corson, T.W.; Crews, C.M. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell,  2007, 130(5), 769-774.
[http://dx.doi.org/10.1016/j.cell.2007.08.021] [PMID:  17803898] 
[6] 
Kushiro, T.; Nambara, E.; McCourt, P. Hormone evolution: The key to signalling. Nature,  2003, 422(6928), 122.
[http://dx.doi.org/10.1038/422122a] [PMID:  12634761] 
[7] 
Howitz, K.T.; Sinclair, D.A. Xenohormesis: sensing the chemical cues of other species. Cell,  2008, 133(3), 387-391.
[http://dx.doi.org/10.1016/j.cell.2008.04.019] [PMID:  18455976] 
[8] 
Vane, J.R.; Anggård, E.E.; Botting, R.M. Regulatory functions of the vascular endothelium. N. Engl. J. Med.,  1990, 323(1), 27-36.
[http://dx.doi.org/10.1056/NEJM199007053230106] [PMID:  2113184] 
[9] 
Endemann, D.H.; Schiffrin, E.L. Endothelial dysfunction. J. Am. Soc. Nephrol.,  2004, 15(8), 1983-1992.
[http://dx.doi.org/10.1097/01.ASN.0000132474.50966.DA] [PMID:  15284284] 
[10] 
Moncada, S.; Higgs, E.A. The discovery of nitric oxide and its role in vascular biology. Br. J. Pharmacol.,  2006, 147(Suppl. 1), S193-S201.
[http://dx.doi.org/10.1038/sj.bjp.0706458] [PMID:  16402104] 
[11] 
Förstermann, U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch.,  2010, 459(6), 923-939.
[http://dx.doi.org/10.1007/s00424-010-0808-2] [PMID:  20306272] 
[12] 
Perez-Vizcaino, F.; Duarte, J. Flavonols and cardiovascular disease. Mol. Aspects Med.,  2010, 31(6), 478-494.
[http://dx.doi.org/10.1016/j.mam.2010.09.002] [PMID:  20837053] 
[13] 
Auger, C.; Chaabi, M.; Anselm, E.; Lobstein, A.; Schini-Kerth, V.B. The red wine extract-induced activation of endothelial nitric oxide synthase is mediated by a great variety of polyphenolic compounds. Mol. Nutr. Food Res.,  2010, 54(Suppl. 2), S171-S183.
[http://dx.doi.org/10.1002/mnfr.200900602] [PMID:  20440695] 
[14] 
Duarte, J.; Francisco, V.; Perez-Vizcaino, F. Modulation of nitric oxide by flavonoids. Food Funct.,  2014, 5(8), 1653-1668.
[http://dx.doi.org/10.1039/C4FO00144C] [PMID:  24901042] 
[15] 
Forte, M.; Conti, V.; Damato, A.; Ambrosio, M.; Puca, A.A.; Sciarretta, S.; Frati, G.; Vecchione, C.; Carrizzo, A. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases. Oxid. Med. Cell. Longev.,  2016, 20167364138
[http://dx.doi.org/10.1155/2016/7364138] [PMID:  27651855] 
[16] 
Duarte, J.; Pérez Vizcaíno, F.; Utrilla, P.; Jiménez, J.; Tamargo, J.; Zarzuelo, A. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships. Gen. Pharmacol.,  1993, 24(4), 857-862.
[http://dx.doi.org/10.1016/0306-3623(93)90159-U] [PMID:  8224739] 
[17] 
Jiménez, R.; Andriambeloson, E.; Duarte, J.; Andriantsitohaina, R.; Jiménez, J.; Pérez-Vizcaino, F.; Zarzuelo, A.; Tamargo, J. Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta. Br. J. Pharmacol.,  1999, 127(7), 1539-1544.
[http://dx.doi.org/10.1038/sj.bjp.0702694] [PMID:  10455307] 
[18] 
Li, Z.; Wang, Y.; Vanhoutte, P.M. Epigallocatechin gallate elicits contractions of the isolated aorta of the aged spontaneously hypertensive rat. Basic Clin. Pharmacol. Toxicol.,  2011, 109(1), 47-55.
[http://dx.doi.org/10.1111/j.1742-7843.2011.00683.x] [PMID:  21310006] 
[19] 
Mawoza, T.; Ojewole, J.A.; Owira, P.M. Contractile effect of Sclerocarya birrea (A Rich) Hochst (Anacardiaceae) (Marula) leaf aqueous extract on rat and rabbit isolated vascular smooth muscles. Cardiovasc. J. Afr.,  2012, 23(1), 12-17.
[http://dx.doi.org/10.5830/CVJA-2010-098] [PMID:  22331245] 
[20] 
Lodi, F.; Jimenez, R.; Moreno, L.; Kroon, P.A.; Needs, P.W.; Hughes, D.A.; Santos-Buelga, C.; Gonzalez-Paramas, A.; Cogolludo, A.; Lopez-Sepulveda, R.; Duarte, J.; Perez-Vizcaino, F. Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. Atherosclerosis,  2009, 204(1), 34-39.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.08.007] [PMID:  18801486] 
[21] 
Suri, S.; Liu, X.H.; Rayment, S.; Hughes, D.A.; Kroon, P.A.; Needs, P.W.; Taylor, M.A.; Tribolo, S.; Wilson, V.G. Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br. J. Pharmacol.,  2010, 159(3), 566-575.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00556.x] [PMID:  20050852] 
[22] 
Leeya, Y.; Mulvany, M.J.; Queiroz, E.F.; Marston, A.; Hostettmann, K.; Jansakul, C. Hypotensive activity of an n-butanol extract and their purified compounds from leaves of Phyllanthus acidus (L.) Skeels in rats. Eur. J. Pharmacol.,  2010, 649(1-3), 301-313.
[http://dx.doi.org/10.1016/j.ejphar.2010.09.038] [PMID:  20868659] 
[23] 
Ibarra, M.; Pérez-Vizcaíno, F.; Cogolludo, A.; Duarte, J.; Zaragozá-Arnáez, F.; López-López, J.G.; Tamargo, J. Cardiovascular effects of isorhamnetin and quercetin in isolated rat and porcine vascular smooth muscle and isolated rat atria. Planta Med.,  2002, 68(4), 307-310.
[http://dx.doi.org/10.1055/s-2002-26752] [PMID:  11988852] 
[24] 
Pérez-Vizcaíno, F.; Ibarra, M.; Cogolludo, A.L.; Duarte, J.; Zaragozá-Arnáez, F.; Moreno, L.; López-López, G.; Tamargo, J. Endothelium-independent vasodilator effects of the flavonoid quercetin and its methylated metabolites in rat conductance and resistance arteries. J. Pharmacol. Exp. Ther.,  2002, 302(1), 66-72.
[http://dx.doi.org/10.1124/jpet.302.1.66] [PMID:  12065701] 
[25] 
Cogolludo, A.; Frazziano, G.; Briones, A.M.; Cobeño, L.; Moreno, L.; Lodi, F.; Salaices, M.; Tamargo, J.; Perez-Vizcaino, F. The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2. Role in vasodilatation. Cardiovasc. Res.,  2007, 73(2), 424-431.
[http://dx.doi.org/10.1016/j.cardiores.2006.09.008] [PMID:  17055466] 
[26] 
Wang, B.; Wu, N.; Liang, F.; Zhang, S.; Ni, W.; Cao, Y.; Xia, D.; Xi, H. 7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats. J. Mol. Histol.,  2014, 45(2), 129-140.
[http://dx.doi.org/10.1007/s10735-013-9539-y] [PMID:  24045895] 
[27] 
Ajay, M.; Gilani, A.U.; Mustafa, M.R. Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci.,  2003, 74(5), 603-612.
[http://dx.doi.org/10.1016/j.lfs.2003.06.039] [PMID:  14623031] 
[28] 
Khoo, N.K.; White, C.R.; Pozzo-Miller, L.; Zhou, F.; Constance, C.; Inoue, T.; Patel, R.P.; Parks, D.A. Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels. Free Radic. Biol. Med.,  2010, 49(3), 339-347.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.04.022] [PMID:  20423726] 
[29] 
Larson, A.; Witman, M.A.; Guo, Y.; Ives, S.; Richardson, R.S.; Bruno, R.S.; Jalili, T.; Symons, J.D. Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. Nutr. Res.,  2012, 32(8), 557-564.
[http://dx.doi.org/10.1016/j.nutres.2012.06.018] [PMID:  22935338] 
[30] 
Kim, J.A.; Formoso, G.; Li, Y.; Potenza, M.A.; Marasciulo, F.L.; Montagnani, M.; Quon, M.J. Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J. Biol. Chem.,  2007, 282(18), 13736-13745.
[http://dx.doi.org/10.1074/jbc.M609725200] [PMID:  17363366] 
[31] 
Wallerath, T.; Poleo, D.; Li, H.; Förstermann, U. Red wine increases the expression of human endothelial nitric oxide synthase: a mechanism that may contribute to its beneficial cardiovascular effects. J. Am. Coll. Cardiol.,  2003, 41(3), 471-478.
[http://dx.doi.org/10.1016/S0735-1097(02)02826-7] [PMID:  12575978] 
[32] 
Wallerath, T.; Li, H.; Gödtel-Ambrust, U.; Schwarz, P.M.; Förstermann, U. A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide,  2005, 12(2), 97-104.
[http://dx.doi.org/10.1016/j.niox.2004.12.004] [PMID:  15740983] 
[33] 
Appeldoorn, M.M.; Venema, D.P.; Peters, T.H.; Koenen, M.E.; Arts, I.C.; Vincken, J.P.; Gruppen, H.; Keijer, J.; Hollman, P.C. Some phenolic compounds increase the nitric oxide level in endothelial cells in vitro. J. Agric. Food Chem.,  2009, 57(17), 7693-7699.
[http://dx.doi.org/10.1021/jf901381x] [PMID:  19722703] 
[34] 
Persson, I.A.; Josefsson, M.; Persson, K.; Andersson, R.G. Tea flavanols inhibit angiotensin-converting enzyme activity and increase nitric oxide production in human endothelial cells. J. Pharm. Pharmacol.,  2006, 58(8), 1139-1144.
[http://dx.doi.org/10.1211/jpp.58.8.0016] [PMID:  16872562] 
[35] 
Ramirez-Sanchez, I.; Maya, L.; Ceballos, G.; Villarreal, F. (-)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells. Am. J. Physiol. Cell Physiol.,  2011, 300(4), C880-C887.
[http://dx.doi.org/10.1152/ajpcell.00406.2010] [PMID:  21209365] 
[36] 
Kurita, I.; Kim, J.H.; Auger, C.; Kinoshita, Y.; Miyase, T.; Ito, T.; Schini-Kerth, V.B. Hydroxylation of (-)-epigallocatechin-3-O-gallate at 3′', but not 4′', is essential for the PI3-kinase/Akt-dependent phosphorylation of endothelial NO synthase in endothelial cells and relaxation of coronary artery rings. Food Funct.,  2013, 4(2), 249-257.
[http://dx.doi.org/10.1039/C2FO30087G] [PMID:  23104077] 
[37] 
Bernátová, I.; Pechánová, O.; Babál, P.; Kyselá, S.; Stvrtina, S.; Andriantsitohaina, R. Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension. Am. J. Physiol. Heart Circ. Physiol.,  2002, 282(3), H942-H948.
[http://dx.doi.org/10.1152/ajpheart.00724.2001] [PMID:  11834490] 
[38] 
Lorenz, M.; Wessler, S.; Follmann, E.; Michaelis, W.; Düsterhöft, T.; Baumann, G.; Stangl, K.; Stangl, V. A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J. Biol. Chem.,  2004, 279(7), 6190-6195.
[http://dx.doi.org/10.1074/jbc.M309114200] [PMID:  14645258] 
[39] 
Grossini, E.; Marotta, P.; Farruggio, S.; Sigaudo, L.; Qoqaiche, F.; Raina, G.; de Giuli, V.; Mary, D.; Vacca, G.; Pollastro, F. Effects of artemetin on nitric oxide release and protection against peroxidative injuries in porcine coronary artery endothelial cells. Phytother. Res.,  2015, 29(9), 1339-1348.
[http://dx.doi.org/10.1002/ptr.5386] [PMID:  26032176] 
[40] 
Ndiaye, M.; Chataigneau, M.; Lobysheva, I.; Chataigneau, T.; Schini-Kerth, V.B. Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive PI3-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J.,  2005, 19(3), 455-457.
[http://dx.doi.org/10.1096/fj.04-2146fje] [PMID:  15623569] 
[41] 
Perez-Vizcaino, F.; Duarte, J.; Andriantsitohaina, R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic. Res.,  2006, 40(10), 1054-1065.
[http://dx.doi.org/10.1080/10715760600823128] [PMID:  17015250] 
[42] 
Anselm, E.; Socorro, V.F.; Dal-Ros, S.; Schott, C.; Bronner, C.; Schini-Kerth, V.B. Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors. J. Cardiovasc. Pharmacol.,  2009, 53(3), 253-260.
[http://dx.doi.org/10.1097/FJC.0b013e31819ccfc9] [PMID:  19247189] 
[43] 
López-López, G.; Moreno, L.; Cogolludo, A.; Galisteo, M.; Ibarra, M.; Duarte, J.; Lodi, F.; Tamargo, J.; Perez-Vizcaino, F. Nitric oxide (NO) scavenging and NO protecting effects of quercetin and their biological significance in vascular smooth muscle. Mol. Pharmacol.,  2004, 65(4), 851-859.
[http://dx.doi.org/10.1124/mol.65.4.851] [PMID:  15044614] 
[44] 
Jackson, S.J.; Venema, R.C. Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J. Nutr.,  2006, 136(5), 1178-1184.
[http://dx.doi.org/10.1093/jn/136.5.1178] [PMID:  16614401] 
[45] 
Tribolo, S.; Lodi, F.; Winterbone, M.S.; Saha, S.; Needs, P.W.; Hughes, D.A.; Kroon, P.A. Human metabolic transformation of quercetin blocks its capacity to decrease endothelial nitric oxide synthase (eNOS) expression and endothelin-1 secretion by human endothelial cells. J. Agric. Food Chem.,  2013, 61(36), 8589-8596.
[http://dx.doi.org/10.1021/jf402511c] [PMID:  23947593] 
[46] 
Sánchez, M.; Galisteo, M.; Vera, R.; Villar, I.C.; Zarzuelo, A.; Tamargo, J.; Pérez-Vizcaíno, F.; Duarte, J. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J. Hypertens.,  2006, 24(1), 75-84.
[http://dx.doi.org/10.1097/01.hjh.0000198029.22472.d9] [PMID:  16331104] 
[47] 
Romero, M.; Jiménez, R.; Hurtado, B.; Moreno, J.M.; Rodríguez-Gómez, I.; López-Sepúlveda, R.; Zarzuelo, A.; Pérez-Vizcaino, F.; Tamargo, J.; Vargas, F.; Duarte, J. Lack of beneficial metabolic effects of quercetin in adult spontaneously hypertensive rats. Eur. J. Pharmacol.,  2010, 627(1-3), 242-250.
[http://dx.doi.org/10.1016/j.ejphar.2009.11.006] [PMID:  19903466] 
[48] 
Sanchez, M.; Lodi, F.; Vera, R.; Villar, I.C.; Cogolludo, A.; Jimenez, R.; Moreno, L.; Romero, M.; Tamargo, J.; Perez-Vizcaino, F.; Duarte, J. Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta. J. Nutr.,  2007, 137(4), 910-915.
[http://dx.doi.org/10.1093/jn/137.4.910] [PMID:  17374653] 
[49] 
Romero, M.; Jiménez, R.; Sánchez, M.; López-Sepúlveda, R.; Zarzuelo, M.J.; O’Valle, F.; Zarzuelo, A.; Pérez-Vizcaíno, F.; Duarte, J. Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis,  2009, 202(1), 58-67.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.03.007] [PMID:  18436224] 
[50] 
Li, Y.; Ying, C.; Zuo, X.; Yi, H.; Yi, W.; Meng, Y.; Ikeda, K.; Ye, X.; Yamori, Y.; Sun, X. Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells. J. Nutr. Biochem.,  2009, 20(12), 1021-1027.
[http://dx.doi.org/10.1016/j.jnutbio.2008.12.001] [PMID:  19195865] 
[51] 
Zheng, Y.; Lim, E.J.; Wang, L.; Smart, E.J.; Toborek, M.; Hennig, B. Role of caveolin-1 in EGCG-mediated protection against linoleic-acid-induced endothelial cell activation. J. Nutr. Biochem.,  2009, 20(3), 202-209.
[http://dx.doi.org/10.1016/j.jnutbio.2008.02.004] [PMID:  18656337] 
[52] 
Kamada, C.; Mukai, R.; Kondo, A.; Sato, S.; Terao, J. Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells. J. Clin. Biochem. Nutr.,  2016, 58(3), 193-201.
[http://dx.doi.org/10.3164/jcbn.16-2] [PMID:  27257344] 
[53] 
Picq, M.; Dubois, M.; Prigent, A.F.; Némoz, G.; Pacheco, H. Inhibition of the different cyclic nucleotide phosphodiesterase isoforms separated from rat brain by flavonoid compounds. Biochem. Int.,  1989, 18(1), 47-57.
[PMID:  2541724] 
[54] 
Duarte, J.; Jiménez, R.; O’Valle, F.; Galisteo, M.; Pérez-Palencia, R.; Vargas, F.; Pérez-Vizcaíno, F.; Zarzuelo, A.; Tamargo, J. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J. Hypertens.,  2002, 20(9), 1843-1854.
[http://dx.doi.org/10.1097/00004872-200209000-00031] [PMID:  12195128] 
[55] 
García-Saura, M.F.; Galisteo, M.; Villar, I.C.; Bermejo, A.; Zarzuelo, A.; Vargas, F.; Duarte, J. Effects of chronic quercetin treatment in experimental renovascular hypertension. Mol. Cell. Biochem.,  2005, 270(1-2), 147-155.
[http://dx.doi.org/10.1007/s11010-005-4503-0] [PMID:  15792364] 
[56] 
Actis-Goretta, L.; Ottaviani, J.I.; Fraga, C.G. Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J. Agric. Food Chem.,  2006, 54(1), 229-234.
[http://dx.doi.org/10.1021/jf052263o] [PMID:  16390204] 
[57] 
Tang, W.J.; Hu, C.P.; Chen, M.F.; Deng, P.Y.; Li, Y.J. Epigallocatechin gallate preserves endothelial function by reducing the endogenous nitric oxide synthase inhibitor level. Can. J. Physiol. Pharmacol.,  2006, 84(2), 163-171.
[http://dx.doi.org/10.1139/y05-156] [PMID:  16900942] 
[58] 
Jiménez, R.; López-Sepúlveda, R.; Kadmiri, M.; Romero, M.; Vera, R.; Sánchez, M.; Vargas, F.; O’Valle, F.; Zarzuelo, A.; Dueñas, M.; Santos-Buelga, C.; Duarte, J. Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase. Free Radic. Biol. Med.,  2007, 43(3), 462-473.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.007] [PMID:  17602962] 
[59] 
Nickel, T.; Hanssen, H.; Sisic, Z.; Pfeiler, S.; Summo, C.; Schmauss, D.; Hoster, E.; Weis, M. Immunoregulatory effects of the flavonol quercetin in vitro and in vivo. Eur. J. Nutr.,  2011, 50(3), 163-172.
[http://dx.doi.org/10.1007/s00394-010-0125-8] [PMID:  20652710] 
[60] 
Gómez-Guzmán, M.; Jiménez, R.; Sánchez, M.; Zarzuelo, M.J.; Galindo, P.; Quintela, A.M.; López-Sepúlveda, R.; Romero, M.; Tamargo, J.; Vargas, F.; Pérez-Vizcaíno, F.; Duarte, J. Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension. Free Radic. Biol. Med.,  2012, 52(1), 70-79.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.015] [PMID:  22001745] 
[61] 
Bors, W.; Michel, C.; Stettmaier, K. Structure-activity relationships governing antioxidant capacities of plant polyphenols. Methods Enzymol.,  2001, 335, 166-180.
[http://dx.doi.org/10.1016/S0076-6879(01)35241-2] [PMID:  11400366] 
[62] 
Fraga, C.G.; Galleano, M.; Verstraeten, S.V.; Oteiza, P.I. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol. Aspects Med.,  2010, 31(6), 435-445.
[http://dx.doi.org/10.1016/j.mam.2010.09.006] [PMID:  20854840] 
[63] 
Procházková, D.; Boušová, I.; Wilhelmová, N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia,  2011, 82(4), 513-523.
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID:  21277359] 
[64] 
Morand, C.; Crespy, V.; Manach, C.; Besson, C.; Demigné, C.; Rémésy, C. Plasma metabolites of quercetin and their antioxidant properties. Am. J. Physiol.,  1998, 275(1), R212-R219.
[PMID:  9688981] 
[65] 
Pollard, S.E.; Kuhnle, G.G.; Vauzour, D.; Vafeiadou, K.; Tzounis, X.; Whiteman, M.; Rice-Evans, C.; Spencer, J.P. The reaction of flavonoid metabolites with peroxynitrite. Biochem. Biophys. Res. Commun.,  2006, 350(4), 960-968.
[http://dx.doi.org/10.1016/j.bbrc.2006.09.131] [PMID:  17045238] 
[66] 
Pannala, A.S.; Rice-Evans, C.A.; Halliwell, B.; Singh, S. Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Biochem. Biophys. Res. Commun.,  1997, 232(1), 164-168.
[http://dx.doi.org/10.1006/bbrc.1997.6254] [PMID:  9125123] 
[67] 
Yokoyama, A.; Sakakibara, H.; Crozier, A.; Kawai, Y.; Matsui, A.; Terao, J.; Kumazawa, S.; Shimoi, K. Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats. Free Radic. Res.,  2009, 43(10), 913-921.
[http://dx.doi.org/10.1080/10715760903137010] [PMID:  19669999] 
[68] 
Žižková, P.; Blaškovič, D.; Májeková, M.; Švorc, L.; Račková, L.; Ratkovská, L.; Veverka, M.; Horáková, L. Novel quercetin derivatives in treatment of peroxynitrite-oxidized SERCA1. Mol. Cell. Biochem.,  2014, 386(1-2), 1-14.
[http://dx.doi.org/10.1007/s11010-013-1839-8] [PMID:  24141791] 
[69] 
Jeong, Y.J.; Choi, Y.J.; Kwon, H.M.; Kang, S.W.; Park, H.S.; Lee, M.; Kang, Y.H. Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids. Br. J. Nutr.,  2005, 93(5), 581-591.
[http://dx.doi.org/10.1079/BJN20041397] [PMID:  15975156] 
[70] 
Aherne, S.A.; O’Brien, N.M. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic. Biol. Med.,  2000, 29(6), 507-514.
[http://dx.doi.org/10.1016/S0891-5849(00)00360-9] [PMID:  11025194] 
[71] 
Huxley, R.R.; Neil, H.A. The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies. Eur. J. Clin. Nutr.,  2003, 57(8), 904-908.
[http://dx.doi.org/10.1038/sj.ejcn.1601624] [PMID:  12879084] 
[72] 
Chang, W.S.; Lee, Y.J.; Lu, F.J.; Chiang, H.C. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res.,  1993, 13(6A), 2165-2170.
[PMID:  8297130] 
[73] 
López-Sepúlveda, R.; Gómez-Guzmán, M.; Zarzuelo, M.J.; Romero, M.; Sánchez, M.; Quintela, A.M.; Galindo, P.; O’Valle, F.; Tamargo, J.; Pérez-Vizcaíno, F.; Duarte, J.; Jiménez, R. Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: role of NADPH oxidase. Clin. Sci. (Lond.),  2011, 120(8), 321-333.
[http://dx.doi.org/10.1042/CS20100311] [PMID:  20977430] 
[74] 
Fernandes, I.; Pérez-Gregorio, R.; Soares, S.; Mateus, N.; de Freitas, V. Wine flavonoids in health and disease prevention. Molecules,  2017, 22(2)E292
[http://dx.doi.org/10.3390/molecules22020292] [PMID:  28216567] 
[75] 
Follmann, M.; Griebenow, N.; Hahn, M.G.; Hartung, I.; Mais, F.J.; Mittendorf, J.; Schäfer, M.; Schirok, H.; Stasch, J.P.; Stoll, F.; Straub, A. The chemistry and biology of soluble guanylate cyclase stimulators and activators. Angew. Chem. Int. Ed. Engl.,  2013, 52(36), 9442-9462.
[http://dx.doi.org/10.1002/anie.201302588] [PMID:  23963798] 
[76] 
San Cheang, W.; Yuen Ngai, C.; Yen Tam, Y.; Yu Tian, X.; Tak Wong, W.; Zhang, Y.; Wai Lau, C.; Chen, Z.Y.; Bian, Z.X.; Huang, Y.; Ping Leung, F. Black tea protects against hypertension-associated endothelial dysfunction through alleviation of endoplasmic reticulum stress. Sci. Rep.,  2015, 5, 10340.
[http://dx.doi.org/10.1038/srep10340] [PMID:  25976123] 
[77] 
Wu, J.; Xu, X.; Li, Y.; Kou, J.; Huang, F.; Liu, B.; Liu, K. Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells. Eur. J. Pharmacol.,  2014, 745, 59-68.
[http://dx.doi.org/10.1016/j.ejphar.2014.09.046] [PMID:  25446924] 
[78] 
Suganya, N.; Bhakkiyalakshmi, E.; Suriyanarayanan, S.; Paulmurugan, R.; Ramkumar, K.M. Quercetin ameliorates tunicamycin-induced endoplasmic reticulum stress in endothelial cells. Cell Prolif.,  2014, 47(3), 231-240.
[http://dx.doi.org/10.1111/cpr.12102] [PMID:  24666891] 
[79] 
Reiter, C.E.; Kim, J.A.; Quon, M.J. Green tea polyphenol epigallocatechin gallate reduces endothelin-1 expression and secretion in vascular endothelial cells: roles for AMP-activated protein kinase, Akt, and FOXO1. Endocrinology,  2010, 151(1), 103-114.
[http://dx.doi.org/10.1210/en.2009-0997] [PMID:  19887561] 
[80] 
Loke, W.M.; Proudfoot, J.M.; Hodgson, J.M.; McKinley, A.J.; Hime, N.; Magat, M.; Stocker, R.; Croft, K.D. Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscler. Thromb. Vasc. Biol.,  2010, 30(4), 749-757.
[http://dx.doi.org/10.1161/ATVBAHA.109.199687] [PMID:  20093625] 
[81] 
Gomez-Guzman, M.; Jimenez, R.; Sanchez, M.; Zarzuelo, M.J.; Galindo, P.; Quintela, A.M.; Romero, M.; Tamargo, J.; Perez-Vizcaino, F.; Duarte, J. Epicatechin restore endothelial function in DOCA-salt hypertension: role of endothelin-1, NADPH oxidase and nrf2 pathways. Basic Clin. Pharmacol. Toxicol.,  2011, 109, 33-33.
[82] 
Schnorr, O.; Brossette, T.; Momma, T.Y.; Kleinbongard, P.; Keen, C.L.; Schroeter, H.; Sies, H. Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo. Arch. Biochem. Biophys.,  2008, 476(2), 211-215.
[http://dx.doi.org/10.1016/j.abb.2008.02.040] [PMID:  18348861] 
[83] 
Scapagnini, G.; Vasto, S.; Abraham, N.G.; Caruso, C.; Zella, D.; Fabio, G.; Calogero, C.; Zella, D.; Fabio, G. Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol. Neurobiol.,  2011, 44(2), 192-201.
[http://dx.doi.org/10.1007/s12035-011-8181-5] [PMID:  21499987] 
[84] 
Kang, C.H.; Choi, Y.H.; Moon, S.K.; Kim, W.J.; Kim, G.Y. Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway. Int. Immunopharmacol.,  2013, 17(3), 808-813.
[http://dx.doi.org/10.1016/j.intimp.2013.09.009] [PMID:  24076371] 
[85] 
Nabavi, S.F.; Barber, A.J.; Spagnuolo, C.; Russo, G.L.; Daglia, M.; Nabavi, S.M.; Sobarzo-Sánchez, E. Nrf2 as molecular target for polyphenols: A novel therapeutic strategy in diabetic retinopathy. Crit. Rev. Clin. Lab. Sci.,  2016, 53(5), 293-312.
[http://dx.doi.org/10.3109/10408363.2015.1129530] [PMID:  26926494] 
[86] 
Nisoli, E.; Tonello, C.; Cardile, A.; Cozzi, V.; Bracale, R.; Tedesco, L.; Falcone, S.; Valerio, A.; Cantoni, O.; Clementi, E.; Moncada, S.; Carruba, M.O. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science,  2005, 310(5746), 314-317.
[http://dx.doi.org/10.1126/science.1117728] [PMID:  16224023] 
[87] 
Zarzuelo, M.J.; López-Sepúlveda, R.; Sánchez, M.; Romero, M.; Gómez-Guzmán, M.; Ungvary, Z.; Pérez-Vizcaíno, F.; Jiménez, R.; Duarte, J. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem. Pharmacol.,  2013, 85(9), 1288-1296.
[http://dx.doi.org/10.1016/j.bcp.2013.02.015] [PMID:  23422569] 
[88] 
Zhang, L.L.; Zhang, H.T.; Cai, Y.Q.; Han, Y.J.; Yao, F.; Yuan, Z.H.; Wu, B.Y. Anti-inflammatory Effect of Mesenchymal Stromal Cell Transplantation and Quercetin Treatment in a Rat Model of Experimental Cerebral Ischemia. Cell. Mol. Neurobiol.,  2016, 36(7), 1023-1034.
[http://dx.doi.org/10.1007/s10571-015-0291-6] [PMID:  27008429] 
[89] 
Bai, B.; Vanhoutte, P.M.; Wang, Y. Loss-of-SIRT1 function during vascular ageing: hyperphosphorylation mediated by cyclin-dependent kinase 5. Trends Cardiovasc. Med.,  2014, 24(2), 81-84.
[http://dx.doi.org/10.1016/j.tcm.2013.07.001] [PMID:  23968571] 
[90] 
Chen, Z.; Peng, I.C.; Cui, X.; Li, Y.S.; Chien, S.; Shyy, J.Y. Shear stress, SIRT1, and vascular homeostasis. Proc. Natl. Acad. Sci. USA,  2010, 107(22), 10268-10273.
[http://dx.doi.org/10.1073/pnas.1003833107] [PMID:  20479254] 
[91] 
Dong, J.; Zhang, X.; Zhang, L.; Bian, H.X.; Xu, N.; Bao, B.; Liu, J. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1. J. Lipid Res.,  2014, 55(3), 363-374.
[http://dx.doi.org/10.1194/jlr.M038786] [PMID:  24465016] 
[92] 
Hung, C.H.; Chan, S.H.; Chu, P.M.; Tsai, K.L. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol. Nutr. Food Res.,  2015, 59(10), 1905-1917.
[http://dx.doi.org/10.1002/mnfr.201500144] [PMID:  26202455] 
[93] 
Chen, C.Y.; Yi, L.; Jin, X.; Zhang, T.; Fu, Y.J.; Zhu, J.D.; Mi, M.T.; Zhang, Q.Y.; Ling, W.H.; Yu, B. Inhibitory effect of delphinidin on monocyte-endothelial cell adhesion induced by oxidized low-density lipoprotein via ROS/p38MAPK/NF-κB pathway. Cell Biochem. Biophys.,  2011, 61(2), 337-348.
[http://dx.doi.org/10.1007/s12013-011-9216-2] [PMID:  21695376] 
[94] 
Indra, M.R.; Karyono, S.; Ratnawati, R.; Malik, S.G. Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs). BMC Res. Notes,  2013, 6, 275.
[http://dx.doi.org/10.1186/1756-0500-6-275] [PMID:  23856194] 
[95] 
Mahmoud, M.F.; Hassan, N.A.; El Bassossy, H.M.; Fahmy, A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PLoS One,  2013, 8(5)e63784
[http://dx.doi.org/10.1371/journal.pone.0063784] [PMID:  23717483] 
[96] 
Yang, J.; Han, Y.; Chen, C.; Sun, H.; He, D.; Guo, J.; Jiang, B.; Zhou, L.; Zeng, C. EGCG attenuates high glucose-induced endothelial cell inflammation by suppression of PKC and NF-κB signaling in human umbilical vein endothelial cells. Life Sci.,  2013, 92(10), 589-597.
[http://dx.doi.org/10.1016/j.lfs.2013.01.025] [PMID:  23395866] 
[97] 
Ma, M.M.; Li, Y.; Liu, X.Y.; Zhu, W.W.; Ren, X.; Kong, G.Q.; Huang, X.; Wang, L.P.; Luo, L.Q.; Wang, X.Z. Cyanidin-3-O-Glucoside ameliorates lipopolysaccharide-induced injury both in vivo and in vitro suppression of NF-κB and MAPK pathways. Inflammation,  2015, 38(4), 1669-1682.
[http://dx.doi.org/10.1007/s10753-015-0144-y] [PMID:  25752620] 
[98] 
Ravishankar, D.; Watson, K.A.; Boateng, S.Y.; Green, R.J.; Greco, F.; Osborn, H.M. Exploring quercetin and luteolin derivatives as antiangiogenic agents. Eur. J. Med. Chem.,  2015, 97, 259-274.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.056] [PMID:  25984842] 
[99] 
Li, Q.; Wang, Y.; Zhang, L.; Chen, L.; Du, Y.; Ye, T.; Shi, X. Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway. Fitoterapia,  2016, 111, 78-86.
[http://dx.doi.org/10.1016/j.fitote.2016.04.015] [PMID:  27105956] 
[100] 
Lee, H.S.; Jun, J.H.; Jung, E.H.; Koo, B.A.; Kim, Y.S. Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular permeability in human retinal pigment epithelial and human retinal microvascular endothelial cells via suppression of MMP-9 and VEGF activation. Molecules,  2014, 19(8), 12150-12172.
[http://dx.doi.org/10.3390/molecules190812150] [PMID:  25123184] 
[101] 
Zhao, J.J.; Song, J.Q.; Pan, S.Y.; Wang, K. Treatment with isorhamnetin protects the brain against ischemic injury in mice. Neurochem. Res.,  2016, 41(8), 1939-1948.
[http://dx.doi.org/10.1007/s11064-016-1904-2] [PMID:  27161367] 
[102] 
Kim, M.H.; Jeong, Y.J.; Cho, H.J.; Hoe, H.S.; Park, K.K.; Park, Y.Y.; Choi, Y.H.; Kim, C.H.; Chang, H.W.; Park, Y.J.; Chung, I.K.; Chang, Y.C. Delphinidin inhibits angiogenesis through the suppression of HIF-1α and VEGF expression in A549 lung cancer cells. Oncol. Rep.,  2017, 37(2), 777-784.
[http://dx.doi.org/10.3892/or.2016.5296] [PMID:  27959445] 
[103] 
Yoshizumi, M.; Tsuchiya, K.; Suzaki, Y.; Kirima, K.; Kyaw, M.; Moon, J.H.; Terao, J.; Tamaki, T. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway. Biochem. Biophys. Res. Commun.,  2002, 293(5), 1458-1465.
[http://dx.doi.org/10.1016/S0006-291X(02)00407-2] [PMID:  12054679] 
[104] 
Zheng, Y.; Song, H.J.; Kim, C.H.; Kim, H.S.; Kim, E.G.; Sachinidis, A.; Ahn, H.Y. Inhibitory effect of epigallocatechin 3-O-gallate on vascular smooth muscle cell hypertrophy induced by angiotensin II. J. Cardiovasc. Pharmacol.,  2004, 43(2), 200-208.
[http://dx.doi.org/10.1097/00005344-200402000-00006] [PMID:  14716206] 
[105] 
Won, S.M.; Park, Y.H.; Kim, H.J.; Park, K.M.; Lee, W.J. Catechins inhibit angiotensin II-induced vascular smooth muscle cell proliferation via mitogen-activated protein kinase pathway. Exp. Mol. Med.,  2006, 38(5), 525-534.
[http://dx.doi.org/10.1038/emm.2006.62] [PMID:  17079869] 
[106] 
Guan, H.; Gao, L.; Zhu, L.; Yan, L.; Fu, M.; Chen, C.; Dong, X.; Wang, L.; Huang, K.; Jiang, H. Apigenin attenuates neointima formation via suppression of vascular smooth muscle cell phenotypic transformation. J. Cell. Biochem.,  2012, 113(4), 1198-1207.
[http://dx.doi.org/10.1002/jcb.23452] [PMID:  22095643] 
[107] 
Schini-Kerth, V.B.; Etienne-Selloum, N.; Chataigneau, T.; Auger, C. Vascular protection by natural product-derived polyphenols: in vitro and in vivo evidence. Planta Med.,  2011, 77(11), 1161-1167.
[http://dx.doi.org/10.1055/s-0030-1250737] [PMID:  21267812] 
[108] 
Jiménez, R.; Duarte, J.; Perez-Vizcaino, F. Epicatechin: endothelial function and blood pressure. J. Agric. Food Chem.,  2012, 60(36), 8823-8830.
[http://dx.doi.org/10.1021/jf205370q] [PMID:  22440087] 
[109] 
Smoliga, J.M.; Vang, O.; Baur, J.A. Challenges of translating basic research into therapeutics: resveratrol as an example. J. Gerontol. A Biol. Sci. Med. Sci.,  2012, 67(2), 158-167.
[http://dx.doi.org/10.1093/gerona/glr062] [PMID:  21746739] 
[110] 
Clark, J.L.; Zahradka, P.; Taylor, C.G. Efficacy of flavonoids in the management of high blood pressure. Nutr. Rev.,  2015, 73(12), 799-822.
[http://dx.doi.org/10.1093/nutrit/nuv048] [PMID:  26491142] 
[111] 
Chen, J.; Lin, H.; Hu, M. Metabolism of flavonoids via enteric recycling: role of intestinal disposition. J. Pharmacol. Exp. Ther.,  2003, 304(3), 1228-1235.
[http://dx.doi.org/10.1124/jpet.102.046409] [PMID:  12604700] 
[112] 
Balzer, J.; Rassaf, T.; Heiss, C.; Kleinbongard, P.; Lauer, T.; Merx, M.; Heussen, N.; Gross, H.B.; Keen, C.L.; Schroeter, H.; Kelm, M. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J. Am. Coll. Cardiol.,  2008, 51(22), 2141-2149.
[http://dx.doi.org/10.1016/j.jacc.2008.01.059] [PMID:  18510961] 
[113] 
Mooradian, A.D.; Haas, M.J. Glucose-induced endoplasmic reticulum stress is independent of oxidative stress: A mechanistic explanation for the failure of antioxidant therapy in diabetes. Free Radic. Biol. Med.,  2011, 50(9), 1140-1143.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.02.002] [PMID:  21320588] 
[114] 
Kay, C.D.; Hooper, L.; Kroon, P.A.; Rimm, E.B.; Cassidy, A. Relative impact of flavonoid composition, dose and structure on vascular function: a systematic review of randomised controlled trials of flavonoid-rich food products. Mol. Nutr. Food Res.,  2012, 56(11), 1605-1616.
[http://dx.doi.org/10.1002/mnfr.201200363] [PMID:  22996837] 
[115] 
Bondonno, C.P.; Liu, A.H.; Croft, K.D.; Ward, N.C.; Yang, X.; Considine, M.J.; Puddey, I.B.; Woodman, R.J.; Hodgson, J.M. Short-term effects of nitrate-rich green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure. Free Radic. Biol. Med.,  2014, 77, 353-362.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.09.021] [PMID:  25261227] 
[116] 
Abdullah, M.M.; Jones, P.J.; Eck, P.K. Nutrigenetics of cholesterol metabolism: observational and dietary intervention studies in the postgenomic era. Nutr. Rev.,  2015, 73(8), 523-543.
[http://dx.doi.org/10.1093/nutrit/nuv016] [PMID:  26117841] 
[117] 
Bondonno, C.P.; Yang, X.; Croft, K.D.; Considine, M.J.; Ward, N.C.; Rich, L.; Puddey, I.B.; Swinny, E.; Mubarak, A.; Hodgson, J.M. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radic. Biol. Med.,  2012, 52(1), 95-102.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.028] [PMID:  22019438] 
[118] 
Gasper, A.; Hollands, W.; Casgrain, A.; Saha, S.; Teucher, B.; Dainty, J.R.; Venema, D.P.; Hollman, P.C.; Rein, M.J.; Nelson, R.; Williamson, G.; Kroon, P.A. Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: a randomized controlled trial. Arch. Biochem. Biophys.,  2014, 559, 29-37.
[http://dx.doi.org/10.1016/j.abb.2014.05.026] [PMID:  24929184] 
[119] 
Heiss, C.; Sansone, R.; Karimi, H.; Krabbe, M.; Schuler, D.; Rodriguez-Mateos, A.; Kraemer, T.; Cortese-Krott, M.M.; Kuhnle, G.G.; Spencer, J.P.; Schroeter, H.; Merx, M.W.; Kelm, M. FLAVIOLA consortium. european union 7th framework program. Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial. Age (Dordr.),  2015, 37(3), 9794.
[http://dx.doi.org/10.1007/s11357-015-9794-9] [PMID:  26013912] 
[120] 
Dower, J.I.; Geleijnse, J.M.; Gijsbers, L.; Zock, P.L.; Kromhout, D.; Hollman, P.C. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial. Am. J. Clin. Nutr.,  2015, 101(5), 914-921.
[http://dx.doi.org/10.3945/ajcn.114.098590] [PMID:  25934864] 
[121] 
Tran, H.; Anand, S.S. Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. JAMA,  2004, 292(15), 1867-1874.
[http://dx.doi.org/10.1001/jama.292.15.1867] [PMID:  15494585] 
[122] 
Freedman, J.E. Oxidative stress and platelets. Arterioscler. Thromb. Vasc. Biol.,  2008, 28(3), s11-s16.
[http://dx.doi.org/10.1161/ATVBAHA.107.159178] [PMID:  18174453] 
[123] 
Park, W.H.; Kim, S.H. Involvement of reactive oxygen species and glutathione in gallic acid-induced human umbilical vein endothelial cell death. Oncol. Rep.,  2012, 28(2), 695-700.
[http://dx.doi.org/10.3892/or.2012.1842] [PMID:  22665164] 
[124] 
Liang, M.L.; Da, X.W.; He, A.D.; Yao, G.Q.; Xie, W.; Liu, G.; Xiang, J.Z.; Ming, Z.Y. Pentamethylquercetin (PMQ) reduces thrombus formation by inhibiting platelet function. Sci. Rep.,  2015, 5, 11142.
[http://dx.doi.org/10.1038/srep11142] [PMID:  26059557] 
[125] 
Yang, Y.; Shi, Z.; Reheman, A.; Jin, J.W.; Li, C.; Wang, Y.; Andrews, M.C.; Chen, P.; Zhu, G.; Ling, W.; Ni, H. Plant food delphinidin-3-glucoside significantly inhibits platelet activation and thrombosis: novel protective roles against cardiovascular diseases. PLoS One,  2012, 7(5) e37323
[http://dx.doi.org/10.1371/journal.pone.0037323] [PMID:  22624015] 
[126] 
Tangney, C.C.; Rasmussen, H.E. Polyphenols, inflammation, and cardiovascular disease. Curr. Atheroscler. Rep.,  2013, 15(5), 324.
[http://dx.doi.org/10.1007/s11883-013-0324-x] [PMID:  23512608] 
[127] 
El Haouari, M.; Rosado, J.A. Medicinal plants with antiplatelet activity. Phytother. Res.,  2016, 30(7), 1059-1071.
[http://dx.doi.org/10.1002/ptr.5619] [PMID:  27062716] 
[128] 
Faggio, C.; Sureda, A.; Morabito, S.; Sanches-Silva, A.; Mocan, A.; Nabavi, S.F.; Nabavi, S.M. Flavonoids and platelet aggregation: A brief review. Eur. J. Pharmacol.,  2017, 807, 91-101.
[http://dx.doi.org/10.1016/j.ejphar.2017.04.009] [PMID:  28412372] 
[129] 
Wright, B.; Spencer, J.P.; Lovegrove, J.A.; Gibbins, J.M. Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs. Cardiovasc. Res.,  2013, 97(1), 13-22.
[http://dx.doi.org/10.1093/cvr/cvs304] [PMID:  23024269] 
[130] 
Hubbard, G.P.; Wolffram, S.; Lovegrove, J.A.; Gibbins, J.M. The role of polyphenolic compounds in the diet as inhibitors of platelet function. Proc. Nutr. Soc.,  2003, 62(2), 469-478.
[http://dx.doi.org/10.1079/PNS2003253] [PMID:  14506895] 
[131] 
Song, F.; Zhu, Y.; Shi, Z.; Tian, J.; Deng, X.; Ren, J.; Andrews, M.C.; Ni, H.; Ling, W.; Yang, Y. Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: Involving the signalling pathway of PI3K-Akt. Thromb. Haemost.,  2014, 112(5), 981-991.
[http://dx.doi.org/10.1160/th13-12-1002] [PMID:  25077916] 
[132] 
Hao, H.Z.; He, A.D.; Wang, D.C.; Yin, Z.; Zhou, Y.J.; Liu, G.; Liang, M.L.; Da, X.W.; Yao, G.Q.; Xie, W.; Xiang, J.Z.; Ming, Z.Y. Antiplatelet activity of loureirin A by attenuating Akt phosphorylation: In vitro studies. Eur. J. Pharmacol.,  2015, 746, 63-69.
[http://dx.doi.org/10.1016/j.ejphar.2014.10.059] [PMID:  25445049] 
[133] 
Luzak, B.; Kassassir, H.; Rój, E.; Stanczyk, L.; Watala, C.; Golanski, J. Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity. Arch. Physiol. Biochem.,  2017, 123(1), 54-60.
[http://dx.doi.org/10.1080/13813455.2016.1247284] [PMID:  27855519] 
[134] 
Choi, J.H.; Kim, K.J.; Kim, S. Comparative effect of quercetin and quercetin-3-O-β-d-glucoside on fibrin polymers, blood clots, and in rodent models. J. Biochem. Mol. Toxicol.,  2016, 30(11), 548-558.
[http://dx.doi.org/10.1002/jbt.21822] [PMID:  27271803] 
[135] 
Hubbard, G.P.; Stevens, J.M.; Cicmil, M.; Sage, T.; Jordan, P.A.; Williams, C.M.; Lovegrove, J.A.; Gibbins, J.M. Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J. Thromb. Haemost.,  2003, 1(5), 1079-1088.
[http://dx.doi.org/10.1046/j.1538-7836.2003.00212.x] [PMID:  12871380] 
[136] 
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, 2012 485262
[http://dx.doi.org/10.1155/2012/485262] [PMID:  23304202] 
[137] 
Guerrero, J.A.; Navarro-Nuñez, L.; Lozano, M.L.; Martínez, C.; Vicente, V.; Gibbins, J.M.; Rivera, J. Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells. Br. J. Clin. Pharmacol.,  2007, 64(2), 133-144.
[http://dx.doi.org/10.1111/j.1365-2125.2007.02881.x] [PMID:  17425630] 
[138] 
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.
[http://dx.doi.org/10.1161/01.CIR.103.23.2792] [PMID:  11401934] 
[139] 
Pignatelli, P.; Di Santo, S.; Buchetti, B.; Sanguigni, V.; Brunelli, A.; Violi, F. Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment. FASEB J.,  2006, 20(8), 1082-1089.
[http://dx.doi.org/10.1096/fj.05-5269com] [PMID:  16770007] 
[140] 
Widlansky, M.E.; Hamburg, N.M.; Anter, E.; Holbrook, M.; Kahn, D.F.; Elliott, J.G.; Keaney, J.F., Jr; Vita, J.A. Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J. Am. Coll. Nutr.,  2007, 26(2), 95-102.
[http://dx.doi.org/10.1080/07315724.2007.10719590] [PMID:  17536120] 
[141] 
Wang, H.P.; Lu, J.F.; Zhang, G.L.; Li, X.Y.; Peng, H.Y.; Lu, Y.; Zhao, L.; Ye, Z.G.; Bruce, I.C.; Xia, Q.; Qian, L.B. Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas. Environ. Toxicol. Pharmacol.,  2014, 38(2), 453-459.
[http://dx.doi.org/10.1016/j.etap.2014.07.019] [PMID:  25136778] 
[142] 
Rechner, A.R.; Kroner, C. Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thromb. Res.,  2005, 116(4), 327-334.
[http://dx.doi.org/10.1016/j.thromres.2005.01.002] [PMID:  16038718] 
[143] 
Heptinstall, S.; May, J.; Fox, S.; Kwik-Uribe, C.; Zhao, L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J. Cardiovasc. Pharmacol.,  2006, 47(Suppl. 2), S197-S205.
[http://dx.doi.org/10.1097/00005344-200606001-00015] [PMID:  16794458] 
[144] 
Keevil, J.G.; Osman, H.E.; Reed, J.D.; Folts, J.D. Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. J. Nutr.,  2000, 130(1), 53-56.
[http://dx.doi.org/10.1093/jn/130.1.53] [PMID:  10613766] 
[145] 
Ostertag, L.M.; Kroon, P.A.; Wood, S.; Horgan, G.W.; Cienfuegos-Jovellanos, E.; Saha, S.; Duthie, G.G.; de Roos, B. Flavan-3-ol-enriched dark chocolate and white chocolate improve acute measures of platelet function in a gender-specific way--a randomized-controlled human intervention trial. Mol. Nutr. Food Res.,  2013, 57(2), 191-202.
[http://dx.doi.org/10.1002/mnfr.201200283] [PMID:  23136121] 
[146] 
Rull, G.; Mohd-Zain, Z.N.; Shiel, J.; Lundberg, M.H.; Collier, D.J.; Johnston, A.; Warner, T.D.; Corder, R. Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation. Vascul. Pharmacol.,  2015, 71, 70-78.
[http://dx.doi.org/10.1016/j.vph.2015.02.010] [PMID:  25869509] 
[147] 
Ottaviani, J.I.; Balz, M.; Kimball, J.; Ensunsa, J.L.; Fong, R.; Momma, T.Y.; Kwik-Uribe, C.; Schroeter, H.; Keen, C.L. Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial. Am. J. Clin. Nutr.,  2015, 102(6), 1425-1435.
[http://dx.doi.org/10.3945/ajcn.115.116178] [PMID:  26537937] 
[148] 
Bundy, J.D.; Li, C.; Stuchlik, P.; Bu, X.; Kelly, T.N.; Mills, K.T.; He, H.; Chen, J.; Whelton, P.K.; He, J. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol.,  2017, 2(7), 775-781.
[http://dx.doi.org/10.1001/jamacardio.2017.1421] [PMID:  28564682] 
[149] 
Carretero, O.A.; Oparil, S. Essential hypertension. Part I: definition and etiology. Circulation,  2000, 101(3), 329-335.
[http://dx.doi.org/10.1161/01.CIR.101.3.329] [PMID:  10645931] 
[150] 
Tamargo, J.; Duarte, J.; Ruilope, L.M. New antihypertensive drugs under development. Curr. Med. Chem.,  2015, 22(3), 305-342.
[http://dx.doi.org/10.2174/0929867321666141106113018] [PMID:  25386825] 
[151] 
Mancia, G.; Fagard, R.; Narkiewicz, K.; Redon, J.; Zanchetti, A.; Böhm, M.; Christiaens, T.; Cifkova, R.; De Backer, G.; Dominiczak, A.; Galderisi, M.; Grobbee, D.E.; Jaarsma, T.; Kirchhof, P.; Kjeldsen, S.E.; Laurent, S.; Manolis, A.J.; Nilsson, P.M.; Ruilope, L.M.; Schmieder, R.E.; Sirnes, P.A.; Sleight, P.; Viigimaa, M.; Waeber, B.; Zannad, F.; Cardiology, T.F.M.A.H.E.S.H.E.S. Task force for the management of arterial hypertension of the european society of hypertension and the european society of cardiology. 2013 ESH/ESC practice guidelines for the management of arterial hypertension. Blood Press.,  2014, 23(1), 3-16.
[http://dx.doi.org/10.3109/08037051.2014.868629] [PMID:  24359485] 
[152] 
Turner, J.M.; Spatz, E.S. Nutritional supplements for the treatment of hypertension: a practical guide for clinicians. Curr. Cardiol. Rep.,  2016, 18(12), 126.
[http://dx.doi.org/10.1007/s11886-016-0806-x] [PMID:  27796863] 
[153] 
Appel, L.J.; Brands, M.W.; Daniels, S.R.; Karanja, N.; Elmer, P.J.; Sacks, F.M.; Association, A.H. American Heart Association. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension,  2006, 47(2), 296-308.
[http://dx.doi.org/10.1161/01.HYP.0000202568.01167.B6] [PMID:  16434724] 
[154] 
Doménech, M.; Roman, P.; Lapetra, J.; García de la Corte, F.J.; Sala-Vila, A.; de la Torre, R.; Corella, D.; Salas-Salvadó, J.; Ruiz-Gutiérrez, V.; Lamuela-Raventós, R.M.; Toledo, E.; Estruch, R.; Coca, A.; Ros, E. Mediterranean diet reduces 24-hour ambulatory blood pressure, blood glucose, and lipids: one-year randomized, clinical trial. Hypertension,  2014, 64(1), 69-76.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.03353] [PMID:  24799608] 
[155] 
Margetts, B.M.; Beilin, L.J.; Vandongen, R.; Armstrong, B.K. Vegetarian diet in mild hypertension: a randomised controlled trial. Br. Med. J. (Clin. Res. Ed.),  1986, 293(6560), 1468-1471.
[http://dx.doi.org/10.1136/bmj.293.6560.1468] [PMID:  3026552] 
[156] 
Appel, L.J.; Moore, T.J.; Obarzanek, E.; Vollmer, W.M.; Svetkey, L.P.; Sacks, F.M.; Bray, G.A.; Vogt, T.M.; Cutler, J.A.; Windhauser, M.M.; Lin, P.H.; Karanja, N. DASH collaborative research group. A clinical trial of the effects of dietary patterns on blood pressure. N. Engl. J. Med.,  1997, 336(16), 1117-1124.
[http://dx.doi.org/10.1056/NEJM199704173361601] [PMID:  9099655] 
[157] 
Reshef, N.; Hayari, Y.; Goren, C.; Boaz, M.; Madar, Z.; Knobler, H. Antihypertensive effect of sweetie fruit in patients with stage I hypertension. Am. J. Hypertens.,  2005, 18(10), 1360-1363.
[http://dx.doi.org/10.1016/j.amjhyper.2005.05.021] [PMID:  16202862] 
[158] 
Cassidy, A.; O’Reilly, É.J.; Kay, C.; Sampson, L.; Franz, M.; Forman, J.P.; Curhan, G.; Rimm, E.B. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am. J. Clin. Nutr.,  2011, 93(2), 338-347.
[http://dx.doi.org/10.3945/ajcn.110.006783] [PMID:  21106916] 
[159] 
Jennings, A.; Welch, A.A.; Fairweather-Tait, S.J.; Kay, C.; Minihane, A.M.; Chowienczyk, P.; Jiang, B.; Cecelja, M.; Spector, T.; Macgregor, A.; Cassidy, A. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am. J. Clin. Nutr.,  2012, 96(4), 781-788.
[http://dx.doi.org/10.3945/ajcn.112.042036] [PMID:  22914551] 
[160] 
Matsuyama, T.; Tanaka, Y.; Kamimaki, I.; Nagao, T.; Tokimitsu, I. Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children. Obesity (Silver Spring),  2008, 16(6), 1338-1348.
[http://dx.doi.org/10.1038/oby.2008.60] [PMID:  18356827] 
[161] 
Grassi, D.; Mulder, T.P.; Draijer, R.; Desideri, G.; Molhuizen, H.O.; Ferri, C. Black tea consumption dose-dependently improves flow-mediated dilation in healthy males. J. Hypertens.,  2009, 27(4), 774-781.
[http://dx.doi.org/10.1097/HJH.0b013e328326066c] [PMID:  19516176] 
[162] 
Peng, X.; Zhou, R.; Wang, B.; Yu, X.; Yang, X.; Liu, K.; Mi, M. Effect of green tea consumption on blood pressure: a meta-analysis of 13 randomized controlled trials. Sci. Rep.,  2014, 4, 6251.
[http://dx.doi.org/10.1038/srep06251] [PMID:  25176280] 
[163] 
Li, G.; Zhang, Y.; Thabane, L.; Mbuagbaw, L.; Liu, A.; Levine, M.A.; Holbrook, A. Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis. J. Hypertens.,  2015, 33(2), 243-254.
[http://dx.doi.org/10.1097/HJH.0000000000000426] [PMID:  25479028] 
[164] 
Grassi, D.; Draijer, R.; Desideri, G.; Mulder, T.; Ferri, C. Black tea lowers blood pressure and wave reflections in fasted and postprandial conditions in hypertensive patients: a randomised study. Nutrients,  2015, 7(2), 1037-1051.
[http://dx.doi.org/10.3390/nu7021037] [PMID:  25658240] 
[165] 
Hodgson, J.M.; Croft, K.D.; Woodman, R.J.; Puddey, I.B.; Fuchs, D.; Draijer, R.; Lukoshkova, E.; Head, G.A. Black tea lowers the rate of blood pressure variation: a randomized controlled trial. Am. J. Clin. Nutr.,  2013, 97(5), 943-950.
[http://dx.doi.org/10.3945/ajcn.112.051375] [PMID:  23553154] 
[166] 
Taubert, D.; Berkels, R.; Roesen, R.; Klaus, W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA,  2003, 290(8), 1029-1030.
[http://dx.doi.org/10.1001/jama.290.8.1029] [PMID:  12941673] 
[167] 
Grassi, D.; Lippi, C.; Necozione, S.; Desideri, G.; Ferri, C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am. J. Clin. Nutr.,  2005, 81(3), 611-614.
[http://dx.doi.org/10.1093/ajcn/81.3.611] [PMID:  15755830] 
[168] 
Taubert, D.; Roesen, R.; Lehmann, C.; Jung, N.; Schömig, E. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA,  2007, 298(1), 49-60.
[http://dx.doi.org/10.1001/jama.298.1.49] [PMID:  17609490] 
[169] 
Fraga, C.G.; Litterio, M.C.; Prince, P.D.; Calabró, V.; Piotrkowski, B.; Galleano, M. Cocoa flavanols: effects on vascular nitric oxide and blood pressure. J. Clin. Biochem. Nutr.,  2011, 48(1), 63-67.
[http://dx.doi.org/10.3164/jcbn.11-010FR] [PMID:  21297914] 
[170] 
Mastroiacovo, D.; Kwik-Uribe, C.; Grassi, D.; Necozione, S.; Raffaele, A.; Pistacchio, L.; Righetti, R.; Bocale, R.; Lechiara, M.C.; Marini, C.; Ferri, C.; Desideri, G. Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study--a randomized controlled trial. Am. J. Clin. Nutr.,  2015, 101(3), 538-548.
[http://dx.doi.org/10.3945/ajcn.114.092189] [PMID:  25733639] 
[171] 
Davinelli, S.; Scapagnini, G. Polyphenols: a promising nutritional approach to prevent or reduce the progression of prehypertension. High Blood Press. Cardiovasc. Prev.,  2016, 23(3), 197-202.
[http://dx.doi.org/10.1007/s40292-016-0149-0] [PMID:  27115149] 
[172] 
López-Sepúlveda, R.; Jiménez, R.; Romero, M.; Zarzuelo, M.J.; Sánchez, M.; Gómez-Guzmán, M.; Vargas, F.; O’Valle, F.; Zarzuelo, A.; Pérez-Vizcaíno, F.; Duarte, J. Wine polyphenols improve endothelial function in large vessels of female spontaneously hypertensive rats. Hypertension,  2008, 51(4), 1088-1095.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.107672] [PMID:  18259008] 
[173] 
Biesinger, S.; Michaels, H.A.; Quadros, A.S.; Qian, Y.; Rabovsky, A.B.; Badger, R.S.; Jalili, T. A combination of isolated phytochemicals and botanical extracts lowers diastolic blood pressure in a randomized controlled trial of hypertensive subjects. Eur. J. Clin. Nutr.,  2016, 70(1), 10-16.
[http://dx.doi.org/10.1038/ejcn.2015.88] [PMID:  26059745] 
[174] 
Rostami, A.; Khalili, M.; Haghighat, N.; Eghtesadi, S.; Shidfar, F.; Heidari, I.; Ebrahimpour-Koujan, S.; Eghtesadi, M. High-cocoa polyphenol-rich chocolate improves blood pressure in patients with diabetes and hypertension. ARYA Atheroscler.,  2015, 11(1), 21-29.
[PMID:  26089927] 
[175] 
Ludovici, V.; Barthelmes, J.; Nägele, M.P.; Enseleit, F.; Ferri, C.; Flammer, A.J.; Ruschitzka, F.; Sudano, I. Cocoa, blood pressure, and vascular function. Front. Nutr.,  2017, 4, 36.
[http://dx.doi.org/10.3389/fnut.2017.00036] [PMID:  28824916] 
[176] 
Ried, K.; Fakler, P.; Stocks, N.P. Effect of cocoa on blood pressure. Cochrane Database Syst. Rev., 2017.
[http://dx.doi.org/10.1002/14651858.CD008893.pub3] 
[177] 
Hodgson, J.M.; Puddey, I.B.; Beilin, L.J.; Mori, T.A.; Burke, V.; Croft, K.D.; Rogers, P.B. Effects of isoflavonoids on blood pressure in subjects with high-normal ambulatory blood pressure levels: a randomized controlled trial. Am. J. Hypertens.,  1999, 12(1 Pt 1), 47-53.
[http://dx.doi.org/10.1016/S0895-7061(98)00216-7] [PMID:  10075384] 
[178] 
Muniyappa, R.; Hall, G.; Kolodziej, T.L.; Karne, R.J.; Crandon, S.K.; Quon, M.J. Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am. J. Clin. Nutr.,  2008, 88(6), 1685-1696.
[http://dx.doi.org/10.3945/ajcn.2008.26457] [PMID:  19064532] 
[179] 
Cano, A.; García-Pérez, M.A.; Tarín, J.J. Isoflavones and cardiovascular disease. Maturitas,  2010, 67(3), 219-226.
[http://dx.doi.org/10.1016/j.maturitas.2010.07.015] [PMID:  20728290] 
[180] 
Dower, J.I.; Geleijnse, J.M.; Gijsbers, L.; Schalkwijk, C.; Kromhout, D.; Hollman, P.C. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre)hypertensive adults: a randomized double-blind, placebo-controlled, crossover trial. J. Nutr.,  2015, 145(7), 1459-1463.
[http://dx.doi.org/10.3945/jn.115.211888] [PMID:  25972527] 
[181] 
Duarte, J.; Pérez-Palencia, R.; Vargas, F.; Ocete, M.A.; Pérez-Vizcaino, F.; Zarzuelo, A.; Tamargo, J. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br. J. Pharmacol.,  2001, 133(1), 117-124.
[http://dx.doi.org/10.1038/sj.bjp.0704064] [PMID:  11325801] 
[182] 
Machha, A.; Mustafa, M.R. Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta. J. Cardiovasc. Pharmacol.,  2005, 46(1), 36-40.
[http://dx.doi.org/10.1097/01.fjc.0000162769.83324.c1] [PMID:  15965352] 
[183] 
Monteiro, M.M.; França-Silva, M.S.; Alves, N.F.; Porpino, S.K.; Braga, V.A. Quercetin improves baroreflex sensitivity in spontaneously hypertensive rats. Molecules,  2012, 17(11), 12997-13008.
[http://dx.doi.org/10.3390/molecules171112997] [PMID:  23117438] 
[184] 
Galindo, P.; González-Manzano, S.; Zarzuelo, M.J.; Gómez-Guzmán, M.; Quintela, A.M.; González-Paramás, A.; Santos-Buelga, C.; Pérez-Vizcaíno, F.; Duarte, J.; Jiménez, R. Different cardiovascular protective effects of quercetin administered orally or intraperitoneally in spontaneously hypertensive rats. Food Funct.,  2012, 3(6), 643-650.
[http://dx.doi.org/10.1039/c2fo10268d] [PMID:  22441211] 
[185] 
Jalili, T.; Carlstrom, J.; Kim, S.; Freeman, D.; Jin, H.; Wu, T.C.; Litwin, S.E.; David Symons, J. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J. Cardiovasc. Pharmacol.,  2006, 47(4), 531-541.
[http://dx.doi.org/10.1097/01.fjc.0000211746.78454.50] [PMID:  16680066] 
[186] 
Häckl, L.P.; Cuttle, G.; Dovichi, S.S.; Lima-Landman, M.T.; Nicolau, M. Inhibition of angiotesin-converting enzyme by quercetin alters the vascular response to brandykinin and angiotensin I. Pharmacology,  2002, 65(4), 182-186.
[http://dx.doi.org/10.1159/000064341] [PMID:  12174832] 
[187] 
Galisteo, M.; García-Saura, M.F.; Jiménez, R.; Villar, I.C.; Wangensteen, R.; Zarzuelo, A.; Vargas, F.; Duarte, J. Effects of quercetin treatment on vascular function in deoxycorticosterone acetate-salt hypertensive rats. Comparative study with verapamil. Planta Med.,  2004, 70(4), 334-341.
[http://dx.doi.org/10.1055/s-2004-818945] [PMID:  15095149] 
[188] 
Aoi, W.; Niisato, N.; Miyazaki, H.; Marunaka, Y. Flavonoid-induced reduction of ENaC expression in the kidney of Dahl salt-sensitive hypertensive rat. Biochem. Biophys. Res. Commun.,  2004, 315(4), 892-896.
[http://dx.doi.org/10.1016/j.bbrc.2004.01.150] [PMID:  14985096] 
[189] 
Mackraj, I.; Govender, T.; Ramesar, S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J. Cardiovasc. Pharmacol.,  2008, 51(3), 239-245.
[http://dx.doi.org/10.1097/FJC.0b013e318162011f] [PMID:  18356687] 
[190] 
Olaleye, M.T.; Crown, O.O.; Akinmoladun, A.C.; Akindahunsi, A.A. Rutin and quercetin show greater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats. Hum. Exp. Toxicol.,  2014, 33(6), 602-608.
[http://dx.doi.org/10.1177/0960327113504790] [PMID:  24064906] 
[191] 
Rivera, L.; Morón, R.; Sánchez, M.; Zarzuelo, A.; Galisteo, M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring),  2008, 16(9), 2081-2087.
[http://dx.doi.org/10.1038/oby.2008.315] [PMID:  18551111] 
[192] 
Yamamoto, Y.; Oue, E. Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci. Biotechnol. Biochem.,  2006, 70(4), 933-939.
[http://dx.doi.org/10.1271/bbb.70.933] [PMID:  16636461] 
[193] 
Perez-Vizcaino, F.; Duarte, J.; Jimenez, R.; Santos-Buelga, C.; Osuna, A. Antihypertensive effects of the flavonoid quercetin. Pharmacol. Rep.,  2009, 61(1), 67-75.
[http://dx.doi.org/10.1016/S1734-1140(09)70008-8] [PMID:  19307694] 
[194] 
Edwards, R.L.; Lyon, T.; Litwin, S.E.; Rabovsky, A.; Symons, J.D.; Jalili, T. Quercetin reduces blood pressure in hypertensive subjects. J. Nutr.,  2007, 137(11), 2405-2411.
[http://dx.doi.org/10.1093/jn/137.11.2405] [PMID:  17951477] 
[195] 
Egert, S.; Bosy-Westphal, A.; Seiberl, J.; Kürbitz, C.; Settler, U.; Plachta-Danielzik, S.; Wagner, A.E.; Frank, J.; Schrezenmeir, J.; Rimbach, G.; Wolffram, S.; Müller, M.J. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br. J. Nutr.,  2009, 102(7), 1065-1074.
[http://dx.doi.org/10.1017/S0007114509359127] [PMID:  19402938] 
[196] 
Egert, S.; Boesch-Saadatmandi, C.; Wolffram, S.; Rimbach, G.; Müller, M.J. Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J. Nutr.,  2010, 140(2), 278-284.
[http://dx.doi.org/10.3945/jn.109.117655] [PMID:  20032478] 
[197] 
Lee, K.H.; Park, E.; Lee, H.J.; Kim, M.O.; Cha, Y.J.; Kim, J.M.; Lee, H.; Shin, M.J. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr. Res. Pract.,  2011, 5(1), 28-33.
[http://dx.doi.org/10.4162/nrp.2011.5.1.28] [PMID:  21487493] 
[198] 
Zahedi, M.; Ghiasvand, R.; Feizi, A.; Asgari, G.; Darvish, L. Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int. J. Prev. Med.,  2013, 4(7), 777-785.
[PMID:  24049596] 
[199] 
Carlstrom, J.; Symons, J.D.; Wu, T.C.; Bruno, R.S.; Litwin, S.E.; Jalili, T. A quercetin supplemented diet does not prevent cardiovascular complications in spontaneously hypertensive rats. J. Nutr.,  2007, 137(3), 628-633.
[http://dx.doi.org/10.1093/jn/137.3.628] [PMID:  17311951] 
[200] 
Brüll, V.; Burak, C.; Stoffel-Wagner, B.; Wolffram, S.; Nickenig, G.; Müller, C.; Langguth, P.; Alteheld, B.; Fimmers, R.; Stehle, P.; Egert, S. Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial. Eur. J. Nutr.,  2017, 56(3), 1347-1357.
[http://dx.doi.org/10.1007/s00394-016-1185-1] [PMID:  26924303] 
[201] 
Serban, M.C.; Sahebkar, A.; Zanchetti, A.; Mikhailidis, D.P.; Howard, G.; Antal, D.; Andrica, F.; Ahmed, A.; Aronow, W.S.; Muntner, P.; Lip, G.Y.; Graham, I.; Wong, N.; Rysz, J.; Banach, M. Lipid and Blood Pressure Meta‐analysis Collaboration (LBPMC) Group. Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Am. Heart Assoc.,  2016, 5(7) e002713
[http://dx.doi.org/10.1161/JAHA.115.002713] [PMID:  27405810] 
[202] 
Vogiatzoglou, A.; Mulligan, A.A.; Lentjes, M.A.; Luben, R.N.; Spencer, J.P.; Schroeter, H.; Khaw, K.T.; Kuhnle, G.G. Flavonoid intake in European adults (18 to 64 years). PLoS One,  2015, 10(5) e0128132
[http://dx.doi.org/10.1371/journal.pone.0128132] [PMID:  26010916] 
[203] 
Perez, A.; Gonzalez-Manzano, S.; Jimenez, R.; Perez-Abud, R.; Haro, J.M.; Osuna, A.; Santos-Buelga, C.; Duarte, J.; Perez-Vizcaino, F. The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: correlation with beta-glucuronidase activity. Pharmacol. Res.,  2014, 89, 11-18.
[http://dx.doi.org/10.1016/j.phrs.2014.07.005] [PMID:  25076013] 
[204] 
Vargas, F.; Romecín, P.; García-Guillén, A.I.; Wangesteen, R.; Vargas-Tendero, P.; Paredes, M.D.; Atucha, N.M.; García-Estañ, J. Flavonoids in kidney health and disease. Front. Physiol.,  2018, 9, 394.
[http://dx.doi.org/10.3389/fphys.2018.00394] [PMID:  29740333] 
[205] 
Conquer, J.A.; Maiani, G.; Azzini, E.; Raguzzini, A.; Holub, B.J. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J. Nutr.,  1998, 128(3), 593-597.
[http://dx.doi.org/10.1093/jn/128.3.593] [PMID:  9482769] 
[206] 
Javadi, F.; Eghtesadi, S.; Ahmadzadeh, A.; Aryaeian, N.; Zabihiyeganeh, M.; Foroushani, A.R.; Jazayeri, S. The effect of quercetin on plasma oxidative status, C-reactive protein and blood pressure in women with rheumatoid arthritis. Int. J. Prev. Med.,  2014, 5(3), 293-301.
[PMID:  24829713] 
[207] 
Brüll, V.; Burak, C.; Stoffel-Wagner, B.; Wolffram, S.; Nickenig, G.; Müller, C.; Langguth, P.; Alteheld, B.; Fimmers, R.; Naaf, S.; Zimmermann, B.F.; Stehle, P.; Egert, S. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br. J. Nutr.,  2015, 114(8), 1263-1277.
[http://dx.doi.org/10.1017/S0007114515002950] [PMID:  26328470] 
[208] 
Duarte, J.; Pérez-Vizcaíno, F.; Zarzuelo, A.; Jiménez, J.; Tamargo, J. Vasodilator effects of quercetin in isolated rat vascular smooth muscle. Eur. J. Pharmacol.,  1993, 239(1-3), 1-7.
[http://dx.doi.org/10.1016/0014-2999(93)90968-N] [PMID:  8223884] 
[209] 
Negishi, H.; Xu, J.W.; Ikeda, K.; Njelekela, M.; Nara, Y.; Yamori, Y. Black and green tea polyphenols attenuate blood pressure increases in stroke-prone spontaneously hypertensive rats. J. Nutr.,  2004, 134(1), 38-42.
[http://dx.doi.org/10.1093/jn/134.1.38] [PMID:  14704290] 
[210] 
Cienfuegos-Jovellanos, E. Quiñones, Mdel.M.; Muguerza, B.; Moulay, L.; Miguel, M.; Aleixandre, A. Antihypertensive effect of a polyphenol-rich cocoa powder industrially processed to preserve the original flavonoids of the cocoa beans. J. Agric. Food Chem.,  2009, 57(14), 6156-6162.
[http://dx.doi.org/10.1021/jf804045b] [PMID:  19537788] 
[211] 
Quiñones, M.; Miguel, M.; Muguerza, B.; Aleixandre, A. Effect of a cocoa polyphenol extract in spontaneously hypertensive rats. Food Funct.,  2011, 2(11), 649-653.
[http://dx.doi.org/10.1039/c1fo10119f] [PMID:  22020342] 
[212] 
Pons, Z.; Margalef, M.; Bravo, F.I.; Arola-Arnal, A.; Muguerza, B. Chronic administration of grape-seed polyphenols attenuates the development of hypertension and improves other cardiometabolic risk factors associated with the metabolic syndrome in cafeteria diet-fed rats. Br. J. Nutr.,  2017, 117(2), 200-208.
[http://dx.doi.org/10.1017/S0007114516004426] [PMID:  28162106] 
[213] 
Quiñones, M.; Margalef, M.; Arola-Arnal, A.; Muguerza, B.; Miguel, M.; Aleixandre, A. The blood pressure effect and related plasma levels of flavan-3-ols in spontaneously hypertensive rats. Food Funct.,  2015, 6(11), 3479-3489.
[http://dx.doi.org/10.1039/C5FO00547G] [PMID:  26294331] 
[214] 
Galleano, M.; Bernatova, I.; Puzserova, A.; Balis, P.; Sestakova, N.; Pechanova, O.; Fraga, C.G. (-)-Epicatechin reduces blood pressure and improves vasorelaxation in spontaneously hypertensive rats by NO-mediated mechanism. IUBMB Life,  2013, 65(8), 710-715.
[http://dx.doi.org/10.1002/iub.1185] [PMID:  23847022] 
[215] 
Kluknavsky, M.; Balis, P.; Puzserova, A.; Radosinska, J.; Berenyiova, A.; Drobna, M.; Lukac, S.; Muchova, J.; Bernatova, I. (-)-Epicatechin prevents blood pressure increase and reduces locomotor hyperactivity in young spontaneously hypertensive rats. Oxid. Med. Cell. Longev.,  2016, 2016 6949020
[http://dx.doi.org/10.1155/2016/6949020] [PMID:  27885334] 
[216] 
Litterio, M.C.; Vazquez Prieto, M.A.; Adamo, A.M.; Elesgaray, R.; Oteiza, P.I.; Galleano, M.; Fraga, C.G. (-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability. J. Nutr. Biochem.,  2015, 26(7), 745-751.
[http://dx.doi.org/10.1016/j.jnutbio.2015.02.004] [PMID:  25943039] 
[217] 
Litterio, M.C.; Jaggers, G.; Sagdicoglu Celep, G.; Adamo, A.M.; Costa, M.A.; Oteiza, P.I.; Fraga, C.G.; Galleano, M. Blood pressure-lowering effect of dietary (-)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels. Free Radic. Biol. Med.,  2012, 53(10), 1894-1902.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.08.585] [PMID:  22985936] 
[218] 
Gómez-Guzmán, M.; Jiménez, R.; Sánchez, M.; Romero, M.; O’Valle, F.; Lopez-Sepulveda, R.; Quintela, A.M.; Galindo, P.; Zarzuelo, M.J.; Bailón, E.; Delpón, E.; Perez-Vizcaino, F.; Duarte, J. Chronic (-)-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats. Br. J. Nutr.,  2011, 106(9), 1337-1348.
[http://dx.doi.org/10.1017/S0007114511004314] [PMID:  21910946] 
[219] 
Piotrkowski, B.; Calabró, V.; Galleano, M.; Fraga, C.G. (-)-Epicatechin prevents alterations in the metabolism of superoxide anion and nitric oxide in the hearts of L-NAME-treated rats. Food Funct.,  2015, 6(1), 155-161.
[http://dx.doi.org/10.1039/C4FO00554F] [PMID:  25361437] 
[220] 
Loke, W.M.; Hodgson, J.M.; Proudfoot, J.M.; McKinley, A.J.; Puddey, I.B.; Croft, K.D. Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am. J. Clin. Nutr.,  2008, 88(4), 1018-1025.
[http://dx.doi.org/10.1093/ajcn/88.4.1018] [PMID:  18842789] 
[221] 
Yamagata, K.; Tagami, M.; Yamori, Y. Dietary polyphenols regulate endothelial function and prevent cardiovascular disease. Nutrition,  2015, 31(1), 28-37.
[http://dx.doi.org/10.1016/j.nut.2014.04.011] [PMID:  25466651] 
[222] 
Buijsse, B.; Weikert, C.; Drogan, D.; Bergmann, M.; Boeing, H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur. Heart J.,  2010, 31(13), 1616-1623.
[http://dx.doi.org/10.1093/eurheartj/ehq068] [PMID:  20354055] 
[223] 
Ried, K.; Sullivan, T.R.; Fakler, P.; Frank, O.R.; Stocks, N.P. Effect of cocoa on blood pressure. Cochrane Database Syst. Rev., 2012, (8) CD008893
[http://dx.doi.org/10.1002/14651858.CD008893.pub2] [PMID:  22895979] 
[224] 
Ellinger, S.; Reusch, A.; Stehle, P.; Helfrich, H.P. Epicatechin ingested via cocoa products reduces blood pressure in humans: a nonlinear regression model with a Bayesian approach. Am. J. Clin. Nutr.,  2012, 95(6), 1365-1377.
[http://dx.doi.org/10.3945/ajcn.111.029330] [PMID:  22552030] 
[225] 
Mangels, D.R.; Mohler, E.R. III Catechins as Potential Mediators of Cardiovascular Health. Arterioscler. Thromb. Vasc. Biol.,  2017, 37(5), 757-763.
[http://dx.doi.org/10.1161/ATVBAHA.117.309048] [PMID:  28336557] 
[226] 
Schroeter, H.; Heiss, C.; Balzer, J.; Kleinbongard, P.; Keen, C.L.; Hollenberg, N.K.; Sies, H.; Kwik-Uribe, C.; Schmitz, H.H.; Kelm, M. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc. Natl. Acad. Sci. USA,  2006, 103(4), 1024-1029.
[http://dx.doi.org/10.1073/pnas.0510168103] [PMID:  16418281] 
[227] 
Igarashi, K.; Honma, K.; Yoshinari, O.; Nanjo, F.; Hara, Y. Effects of dietary catechins on glucose tolerance, blood pressure and oxidative status in Goto-Kakizaki rats. J. Nutr. Sci. Vitaminol. (Tokyo),  2007, 53(6), 496-500.
[http://dx.doi.org/10.3177/jnsv.53.496] [PMID:  18202537] 
[228] 
Mozaffarian, D.; Benjamin, E.J.; Go, A.S.; Arnett, D.K.; Blaha, M.J.; Cushman, M.; Das, S.R.; de Ferranti, S.; Després, J.P.; Fullerton, H.J.; Howard, V.J.; Huffman, M.D.; Isasi, C.R.; Jiménez, M.C.; Judd, S.E.; Kissela, B.M.; Lichtman, J.H.; Lisabeth, L.D.; Liu, S.; Mackey, R.H.; Magid, D.J.; McGuire, D.K.; Mohler, E.R., III; Moy, C.S.; Muntner, P.; Mussolino, M.E.; Nasir, K.; Neumar, R.W.; Nichol, G.; Palaniappan, L.; Pandey, D.K.; Reeves, M.J.; Rodriguez, C.J.; Rosamond, W.; Sorlie, P.D.; Stein, J.; Towfighi, A.; Turan, T.N.; Virani, S.S.; Woo, D.; Yeh, R.W.; Turner, M.B.; Members, W.G.; Committee, A.H.A.S.; Subcommittee, S.S. Writing group members; american heart association statistics committee; stroke statistics subcommittee. heart disease and stroke statistics-2016 update: a report from the american heart association. Circulation,  2016, 133(4), e38-e360.
[http://dx.doi.org/10.1161/CIR.0000000000000350] [PMID:  26673558] 
[229] 
Förstermann, U.; Xia, N.; Li, H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ. Res.,  2017, 120(4), 713-735.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309326] [PMID:  28209797] 
[230] 
Herrington, W.; Lacey, B.; Sherliker, P.; Armitage, J.; Lewington, S. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circ. Res.,  2016, 118(4), 535-546.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.307611] [PMID:  26892956] 
[231] 
Rathee, P.; Chaudhary, H.; Rathee, S.; Rathee, D.; Kumar, V.; Kohli, K. Mechanism of action of flavonoids as anti-inflammatory agents: a review. Inflamm. Allergy Drug Targets,  2009, 8(3), 229-235.
[http://dx.doi.org/10.2174/187152809788681029] [PMID:  19601883] 
[232] 
Siasos, G.; Tousoulis, D.; Tsigkou, V.; Kokkou, E.; Oikonomou, E.; Vavuranakis, M.; Basdra, E.K.; Papavassiliou, A.G.; Stefanadis, C. Flavonoids in atherosclerosis: an overview of their mechanisms of action. Curr. Med. Chem.,  2013, 20(21), 2641-2660.
[http://dx.doi.org/10.2174/0929867311320210003] [PMID:  23627935] 
[233] 
Kokkou, E.; Siasos, G.; Georgiopoulos, G.; Oikonomou, E.; Verveniotis, A.; Vavuranakis, M.; Zisimos, K.; Plastiras, A.; Kollia, M.E.; Stefanadis, C.; Papavassiliou, A.G.; Tousoulis, D. The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment. Atherosclerosis,  2016, 251, 266-272.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.06.054] [PMID:  27428294] 
[234] 
Lin, W.; Wang, W.; Wang, D.; Ling, W. Quercetin protects against atherosclerosis by inhibiting dendritic cell activation. Mol. Nutr. Food Res.,  2017, 61(9)
[http://dx.doi.org/10.1002/mnfr.201700031] [PMID:  28457022] 
[235] 
Cirillo, P.; Conte, S.; Cimmino, G.; Pellegrino, G.; Ziviello, F.; Barra, G.; Sasso, F.C.; Borgia, F.; De Palma, R.; Trimarco, B. Nobiletin inhibits oxidized-LDL mediated expression of Tissue Factor in human endothelial cells through inhibition of NF-κB. Biochem. Pharmacol.,  2017, 128, 26-33.
[http://dx.doi.org/10.1016/j.bcp.2016.12.016] [PMID:  28017776] 
[236] 
Xiao, L.; Liu, L.; Guo, X.; Zhang, S.; Wang, J.; Zhou, F.; Liu, L.; Tang, Y.; Yao, P. Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice: A critical role of NADPH oxidase. Food Chem. Toxicol.,  2017, 105, 22-33.
[http://dx.doi.org/10.1016/j.fct.2017.03.048] [PMID:  28351769] 
[237] 
Kawai, Y.; Nishikawa, T.; Shiba, Y.; Saito, S.; Murota, K.; Shibata, N.; Kobayashi, M.; Kanayama, M.; Uchida, K.; Terao, J. Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. J. Biol. Chem.,  2008, 283(14), 9424-9434.
[http://dx.doi.org/10.1074/jbc.M706571200] [PMID:  18199750] 
[238] 
Phie, J.; Krishna, S.M.; Moxon, J.V.; Omer, S.M.; Kinobe, R.; Golledge, J. Flavonols reduce aortic atherosclerosis lesion area in apolipoprotein E deficient mice: A systematic review and meta-analysis. PLoS One,  2017, 12(7) e0181832
[http://dx.doi.org/10.1371/journal.pone.0181832] [PMID:  28742839] 
[239] 
Liu, T.T.; Zeng, Y.; Tang, K.; Chen, X.; Zhang, W.; Xu, X.L. Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice. Atherosclerosis,  2017, 262, 39-50.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.003] [PMID:  28500865] 
[240] 
Bolduc, V.; Baraghis, E.; Duquette, N.; Thorin-Trescases, N.; Lambert, J.; Lesage, F.; Thorin, E. Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr-/-:hApoB+/+ mice and improves cerebral blood flow. Am. J. Physiol. Heart Circ. Physiol.,  2012, 302(6), H1330-H1339.
[http://dx.doi.org/10.1152/ajpheart.01044.2011] [PMID:  22268108] 
[241] 
Jia, Z.; Nallasamy, P.; Liu, D.; Shah, H.; Li, J.Z.; Chitrakar, R.; Si, H.; McCormick, J.; Zhu, H.; Zhen, W.; Li, Y. Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IKBα/NF-κB signaling pathway. J. Nutr. Biochem.,  2015, 26(3), 293-302.
[http://dx.doi.org/10.1016/j.jnutbio.2014.11.008] [PMID:  25577468] 
[242] 
Yoshida, H.; Watanabe, H.; Ishida, A.; Watanabe, W.; Narumi, K.; Atsumi, T.; Sugita, C.; Kurokawa, M. Naringenin suppresses macrophage infiltration into adipose tissue in an early phase of high-fat diet-induced obesity. Biochem. Biophys. Res. Commun.,  2014, 454(1), 95-101.
[http://dx.doi.org/10.1016/j.bbrc.2014.10.038] [PMID:  25450363] 
[243] 
Liu, L.; Liao, P.; Wang, B.; Fang, X.; Li, W.; Guan, S. Baicalin inhibits the expression of monocyte chemoattractant protein-1 and interleukin-6 in the kidneys of apolipoprotein E-knockout mice fed a high cholesterol diet. Mol. Med. Rep.,  2015, 11(5), 3976-3980.
[http://dx.doi.org/10.3892/mmr.2015.3186] [PMID:  25586053] 
[244] 
Yin, J.; Huang, F.; Yi, Y.; Yin, L.; Peng, D. EGCG attenuates atherosclerosis through the Jagged-1/Notch pathway. Int. J. Mol. Med.,  2016, 37(2), 398-406.
[http://dx.doi.org/10.3892/ijmm.2015.2422] [PMID:  26648562] 
[245] 
Wang, S.; Zhang, X.; Liu, M.; Luan, H.; Ji, Y.; Guo, P.; Wu, C. Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages. Pharm. Biol.,  2015, 53(10), 1481-1487.
[http://dx.doi.org/10.3109/13880209.2014.986688] [PMID:  25857322] 
[246] 
Millar, C.L.; Duclos, Q.; Blesso, C.N. Effects of dietary flavonoids on reverse cholesterol transport, HDL metabolism, and HDL function. Adv. Nutr.,  2017, 8(2), 226-239.
[http://dx.doi.org/10.3945/an.116.014050] [PMID:  28298268] 
[247] 
Chistiakov, D.A.; Melnichenko, A.A.; Orekhov, A.N.; Bobryshev, Y.V. Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie,  2017, 132, 19-27.
[http://dx.doi.org/10.1016/j.biochi.2016.10.010] [PMID:  27771368] 
[248] 
Boesch-Saadatmandi, C.; Pospissil, R.T.; Graeser, A.C.; Canali, R.; Boomgaarden, I.; Doering, F.; Wolffram, S.; Egert, S.; Mueller, M.J.; Rimbach, G. Effect of quercetin on paraoxonase 2 levels in RAW264.7 macrophages and in human monocytes--role of quercetin metabolism. Int. J. Mol. Sci.,  2009, 10(9), 4168-4177.
[http://dx.doi.org/10.3390/ijms10094168] [PMID:  19865538] 
[249] 
Boesch-Saadatmandi, C.; Egert, S.; Schrader, C.; Coumoul, X.; Barouki, R.; Muller, M.J.; Wolffram, S.; Rimbach, G.; Rimbach, G. Effect of quercetin on paraoxonase 1 activity--studies in cultured cells, mice and humans. J. Physiol. Pharmacol.,  2010, 61(1), 99-105.
[PMID:  20228421] 
[250] 
Jaiswal, N.; Rizvi, S.I. Onion extract (Allium cepa L.), quercetin and catechin up-regulate paraoxonase 1 activity with concomitant protection against low-density lipoprotein oxidation in male Wistar rats subjected to oxidative stress. J. Sci. Food Agric.,  2014, 94(13), 2752-2757.
[http://dx.doi.org/10.1002/jsfa.6620] [PMID:  25328927] 
[251] 
Argani, H.; Ghorbanihaghjo, A.; Vatankhahan, H.; Rashtchizadeh, N.; Raeisi, S.; Ilghami, H. The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. Sao Paulo Med. J.,  2016, 134(3), 234-239.
[http://dx.doi.org/10.1590/1516-3180.2015.01702312] [PMID:  27191247] 
[252] 
Fernández-Castillejo, S.; García-Heredia, A.I.; Solà, R.; Camps, J.; López de la Hazas, M.C.; Farràs, M.; Pedret, A.; Catalán, Ú.; Rubió, L.; Motilva, M.J.; Castañer, O.; Covas, M.I.; Valls, R.M. Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial. Mol. Nutr. Food Res.,  2017, 61(10)
[http://dx.doi.org/10.1002/mnfr.201600932] [PMID:  28544610] 
[253] 
Mozos, I.; Malainer, C.; Horbańczuk, J.; Gug, C.; Stoian, D.; Luca, C.T.; Atanasov, A.G. Inflammatory markers for arterial stiffness in cardiovascular diseases. Front. Immunol.,  2017, 8, 1058.
[http://dx.doi.org/10.3389/fimmu.2017.01058] [PMID:  28912780] 
[254] 
Li, G.; Morris-Blanco, K.C.; Lopez, M.S.; Yang, T.; Zhao, H.; Vemuganti, R.; Luo, Y. Impact of microRNAs on ischemic stroke: From pre- to post-disease. Prog. Neurobiol.,  2018, 163-164, 59-78.
[http://dx.doi.org/10.1016/j.pneurobio.2017.08.002] [PMID:  28842356] 
[255] 
Baselga-Escudero, L.; Arola-Arnal, A.; Pascual-Serrano, A.; Ribas-Latre, A.; Casanova, E.; Salvadó, M.J.; Arola, L.; Blade, C. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats. PLoS One,  2013, 8(7) e69817
[http://dx.doi.org/10.1371/journal.pone.0069817] [PMID:  23922812] 
[256] 
Boesch-Saadatmandi, C.; Loboda, A.; Wagner, A.E.; Stachurska, A.; Jozkowicz, A.; Dulak, J.; Döring, F.; Wolffram, S.; Rimbach, G. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155. J. Nutr. Biochem.,  2011, 22(3), 293-299.
[http://dx.doi.org/10.1016/j.jnutbio.2010.02.008] [PMID:  20579867] 
[257] 
Wang, D.; Xia, M.; Yan, X.; Li, D.; Wang, L.; Xu, Y.; Jin, T.; Ling, W. Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circ. Res.,  2012, 111(8), 967-981.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.266502] [PMID:  22821931] 
[258] 
Spector, R. New insight into the dietary cause of atherosclerosis: Implications for pharmacology. J. Pharmacol. Exp. Ther.,  2016, 358(1), 103-108.
[http://dx.doi.org/10.1124/jpet.116.233296] [PMID:  27189968] 
[259] 
Li, D.Y.; Tang, W.H.W. Gut microbiota and atherosclerosis. Curr. Atheroscler. Rep.,  2017, 19(10), 39.
[http://dx.doi.org/10.1007/s11883-017-0675-9] [PMID:  28842845] 
[260] 
Subramaniam, S.; Fletcher, C. Trimethylamine N-oxide: breathe new life. Br. J. Pharmacol.,  2018, 175(8), 1344-1353.
[http://dx.doi.org/10.1111/bph.13959] [PMID:  28745401] 
[261] 
Ren, D.; Liu, Y.; Zhao, Y.; Yang, X. Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice. Food Chem. Toxicol.,  2016, 94, 203-212.
[http://dx.doi.org/10.1016/j.fct.2016.06.004] [PMID:  27316781] 
[262] 
Salden, B.N.; Troost, F.J.; de Groot, E.; Stevens, Y.R.; Garcés-Rimón, M.; Possemiers, S.; Winkens, B.; Masclee, A.A. Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals. Am. J. Clin. Nutr.,  2016, 104(6), 1523-1533.
[http://dx.doi.org/10.3945/ajcn.116.136960] [PMID:  27797708] 
[263] 
Pfeuffer, M.; Auinger, A.; Bley, U.; Kraus-Stojanowic, I.; Laue, C.; Winkler, P.; Rüfer, C.E.; Frank, J.; Bösch-Saadatmandi, C.; Rimbach, G.; Schrezenmeir, J. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr. Metab. Cardiovasc. Dis.,  2013, 23(5), 403-409.
[http://dx.doi.org/10.1016/j.numecd.2011.08.010] [PMID:  22118955] 
[264] 
Zhu, Y.; Ling, W.; Guo, H.; Song, F.; Ye, Q.; Zou, T.; Li, D.; Zhang, Y.; Li, G.; Xiao, Y.; Liu, F.; Li, Z.; Shi, Z.; Yang, Y. Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial. Nutr. Metab. Cardiovasc. Dis.,  2013, 23(9), 843-849.
[http://dx.doi.org/10.1016/j.numecd.2012.06.005] [PMID:  22906565] 
[265] 
Sung, K.C.; Jeong, W.S.; Wild, S.H.; Byrne, C.D. Combined influence of insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes. Diabetes Care,  2012, 35(4), 717-722.
[http://dx.doi.org/10.2337/dc11-1853] [PMID:  22338098] 
[266] 
Kong, A.P.; Luk, A.O.; Chan, J.C. Detecting people at high risk of type 2 diabetes- How do we find them and who should be treated? Best Pract. Res. Clin. Endocrinol. Metab.,  2016, 30(3), 345-355.
[http://dx.doi.org/10.1016/j.beem.2016.06.003] [PMID:  27432070] 
[267] 
Yaghootkar, H.; Scott, R.A.; White, C.C.; Zhang, W.; Speliotes, E.; Munroe, P.B.; Ehret, G.B.; Bis, J.C.; Fox, C.S.; Walker, M.; Borecki, I.B.; Knowles, J.W.; Yerges-Armstrong, L.; Ohlsson, C.; Perry, J.R.; Chambers, J.C.; Kooner, J.S.; Franceschini, N.; Langenberg, C.; Hivert, M.F.; Dastani, Z.; Richards, J.B.; Semple, R.K.; Frayling, T.M. Genetic evidence for a normal-weight “metabolically obese” phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes,  2014, 63(12), 4369-4377.
[http://dx.doi.org/10.2337/db14-0318] [PMID:  25048195] 
[268] 
Lee, S.; Dong, H.H. FoxO integration of insulin signaling with glucose and lipid metabolism. J. Endocrinol.,  2017, 233(2), R67-R79.
[http://dx.doi.org/10.1530/JOE-17-0002] [PMID:  28213398] 
[269] 
João, A.L.; Reis, F.; Fernandes, R. The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond. Obes. Rev.,  2016, 17(7), 553-572.
[http://dx.doi.org/10.1111/obr.12421] [PMID:  27125902] 
[270] 
Savage, D.B.; Petersen, K.F.; Shulman, G.I. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol. Rev.,  2007, 87(2), 507-520.
[http://dx.doi.org/10.1152/physrev.00024.2006] [PMID:  17429039] 
[271] 
Bashan, N.; Kovsan, J.; Kachko, I.; Ovadia, H.; Rudich, A. Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiol. Rev.,  2009, 89(1), 27-71.
[http://dx.doi.org/10.1152/physrev.00014.2008] [PMID:  19126754] 
[272] 
Keane, K.N.; Calton, E.K.; Carlessi, R.; Hart, P.H.; Newsholme, P. The bioenergetics of inflammation: insights into obesity and type 2 diabetes. Eur. J. Clin. Nutr.,  2017, 71(7), 904-912.
[http://dx.doi.org/10.1038/ejcn.2017.45] [PMID:  28402325] 
[273] 
Patel, T.P.; Rawal, K.; Bagchi, A.K.; Akolkar, G.; Bernardes, N.; Dias, D.D.S.; Gupta, S.; Singal, P.K. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Fail. Rev.,  2016, 21(1), 11-23.
[http://dx.doi.org/10.1007/s10741-015-9515-6] [PMID:  26542377] 
[274] 
Boden, G.; Salehi, S. Why does obesity increase the risk for cardiovascular disease? Curr. Pharm. Des.,  2013, 19(32), 5678-5683.
[http://dx.doi.org/10.2174/1381612811319320003] [PMID:  23448485] 
[275] 
King, R.J.; Grant, P.J. Diabetes and cardiovascular disease: pathophysiology of a life-threatening epidemic. Herz,  2016, 41(3), 184-192.
[http://dx.doi.org/10.1007/s00059-016-4414-8] [PMID:  27026400] 
[276] 
Lorber, D. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes Metab. Syndr. Obes.,  2014, 7, 169-183.
[http://dx.doi.org/10.2147/DMSO.S61438] [PMID:  24920930] 
[277] 
Berghöfer, A.; Pischon, T.; Reinhold, T.; Apovian, C.M.; Sharma, A.M.; Willich, S.N. Obesity prevalence from a European perspective: a systematic review. BMC Public Health,  2008, 8, 200.
[http://dx.doi.org/10.1186/1471-2458-8-200] [PMID:  18533989] 
[278] 
Swinburn, B.A.; Sacks, G.; Hall, K.D.; McPherson, K.; Finegood, D.T.; Moodie, M.L.; Gortmaker, S.L. The global obesity pandemic: shaped by global drivers and local environments. Lancet,  2011, 378(9793), 804-814.
[http://dx.doi.org/10.1016/S0140-6736(11)60813-1] [PMID:  21872749] 
[279] 
Burke, L.E.; Wang, J. Treatment strategies for overweight and obesity. J. Nurs. Scholarsh.,  2011, 43(4), 368-375.
[http://dx.doi.org/10.1111/j.1547-5069.2011.01424.x] [PMID:  22018175] 
[280] 
Fan, J.G.; Kim, S.U.; Wong, V.W. New trends on obesity and NAFLD in Asia. J. Hepatol.,  2017, 67(4), 862-873.
[http://dx.doi.org/10.1016/j.jhep.2017.06.003] [PMID:  28642059] 
[281] 
Kawser Hossain, M.; Abdal Dayem, A.; Han, J.; Yin, Y.; Kim, K.; Kumar Saha, S.; Yang, G.M.; Choi, H.Y.; Cho, S.G. Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids. Int. J. Mol. Sci.,  2016, 17(4), 569.
[http://dx.doi.org/10.3390/ijms17040569] [PMID:  27092490] 
[282] 
Gonçalves, R.; Mateus, N.; de Freitas, V. Study of the interaction of pancreatic lipase with procyanidins by optical and enzymatic methods. J. Agric. Food Chem.,  2010, 58(22), 11901-11906.
[http://dx.doi.org/10.1021/jf103026x] [PMID:  21028873] 
[283] 
Rahim, A.T.M.A.; Takahashi, Y.; Yamaki, K. Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non-flavonoid polyphenols. Food Res. Int.,  2015, 75, 289-294.
[http://dx.doi.org/10.1016/j.foodres.2015.05.017] [PMID:  28454959] 
[284] 
Chen, T.; Li, Y.; Zhang, L. Nine different chemical species and action mechanisms of pancreatic lipase ligands screened out from forsythia suspensa leaves all at one time. Molecules,  2017, 22(5) E795
[http://dx.doi.org/10.3390/molecules22050795] [PMID:  28498356] 
[285] 
Yuda, N.; Tanaka, M.; Suzuki, M.; Asano, Y.; Ochi, H.; Iwatsuki, K. Polyphenols extracted from black tea (Camellia sinensis) residue by hot-compressed water and their inhibitory effect on pancreatic lipase in vitro. J. Food Sci.,  2012, 77(12), H254-H261.
[http://dx.doi.org/10.1111/j.1750-3841.2012.02967.x] [PMID:  23106349] 
[286] 
Tadera, K.; Minami, Y.; Takamatsu, K.; Matsuoka, T. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J. Nutr. Sci. Vitaminol. (Tokyo),  2006, 52(2), 149-153.
[http://dx.doi.org/10.3177/jnsv.52.149] [PMID:  16802696] 
[287] 
Kim, Y.; Keogh, J.B.; Clifton, P.M. Polyphenols and glycemic control. Nutrients,  2016, 8(1) E17
[http://dx.doi.org/10.3390/nu8010017] [PMID:  26742071] 
[288] 
Williamson, G. Possible effects of dietary polyphenols on sugar absorption and digestion. Mol. Nutr. Food Res.,  2013, 57(1), 48-57.
[http://dx.doi.org/10.1002/mnfr.201200511] [PMID:  23180627] 
[289] 
Lin, S.T.; Tu, S.H.; Yang, P.S.; Hsu, S.P.; Lee, W.H.; Ho, C.T.; Wu, C.H.; Lai, Y.H.; Chen, M.Y.; Chen, L.C. Apple Polyphenol Phloretin Inhibits Colorectal Cancer Cell Growth via Inhibition of the Type 2 Glucose Transporter and Activation of p53-Mediated Signaling. J. Agric. Food Chem.,  2016, 64(36), 6826-6837.
[http://dx.doi.org/10.1021/acs.jafc.6b02861] [PMID:  27538679] 
[290] 
Brito, A.F.; Ribeiro, M.; Abrantes, A.M.; Mamede, A.C.; Laranjo, M.; Casalta-Lopes, J.E.; Gonçalves, A.C.; Sarmento-Ribeiro, A.B.; Tralhão, J.G.; Botelho, M.F. New approach for treatment of primary liver tumors: the role of quercetin. Nutr. Cancer,  2016, 68(2), 250-266.
[http://dx.doi.org/10.1080/01635581.2016.1145245] [PMID:  26943884] 
[291] 
Yang, Y.; Wolfram, J.; Boom, K.; Fang, X.; Shen, H.; Ferrari, M. Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem. Funct.,  2013, 31(5), 374-379.
[http://dx.doi.org/10.1002/cbf.2905] [PMID:  23042260] 
[292] 
Nakao, Y.; Yoshihara, H.; Fujimori, K. Suppression of very early stage of adipogenesis by baicalein, a plant-derived flavonoid through reduced akt-c/ebpα-glut4 signaling-mediated glucose uptake in 3T3-L1 adipocytes. PLoS One,  2016, 11(9) e0163640
[http://dx.doi.org/10.1371/journal.pone.0163640] [PMID:  27669565] 
[293] 
Hsu, C.C.; Lin, M.H.; Cheng, J.T.; Wu, M.C. Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β-endorphin in type I-like diabetic rats. Clin. Exp. Pharmacol. Physiol.,  2017, 44(5), 549-555.
[http://dx.doi.org/10.1111/1440-1681.12739] [PMID:  28218955] 
[294] 
Dhanya, R.; Arun, K.B.; Syama, H.P.; Nisha, P.; Sundaresan, A.; Santhosh Kumar, T.R.; Jayamurthy, P. Rutin and quercetin enhance glucose uptake in L6 myotubes under oxidative stress induced by tertiary butyl hydrogen peroxide. Food Chem.,  2014, 158, 546-554.
[http://dx.doi.org/10.1016/j.foodchem.2014.02.151] [PMID:  24731381] 
[295] 
Lin, C.H.; Wu, J.B.; Jian, J.Y.; Shih, C.C. (-)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice. PLoS One,  2017, 12(3)e0173984
[http://dx.doi.org/10.1371/journal.pone.0173984] [PMID:  28333970] 
[296] 
Kim, S.; Go, G.W.; Imm, J.Y. Promotion of glucose uptake in C2C12 myotubes by cereal flavone tricin and its underlying molecular mechanism. J. Agric. Food Chem.,  2017, 65(19), 3819-3826.
[http://dx.doi.org/10.1021/acs.jafc.7b00578] [PMID:  28474889] 
[297] 
Steckhan, N.; Hohmann, C.D.; Kessler, C.; Dobos, G.; Michalsen, A.; Cramer, H. Effects of different dietary approaches on inflammatory markers in patients with metabolic syndrome: A systematic review and meta-analysis. Nutrition,  2016, 32(3), 338-348.
[http://dx.doi.org/10.1016/j.nut.2015.09.010] [PMID:  26706026] 
[298] 
Rains, T.M.; Agarwal, S.; Maki, K.C. Antiobesity effects of green tea catechins: a mechanistic review. J. Nutr. Biochem.,  2011, 22(1), 1-7.
[http://dx.doi.org/10.1016/j.jnutbio.2010.06.006] [PMID:  21115335] 
[299] 
Dulloo, A.G.; Duret, C.; Rohrer, D.; Girardier, L.; Mensi, N.; Fathi, M.; Chantre, P.; Vandermander, J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am. J. Clin. Nutr.,  1999, 70(6), 1040-1045.
[http://dx.doi.org/10.1093/ajcn/70.6.1040] [PMID:  10584049] 
[300] 
Phung, O.J.; Baker, W.L.; Matthews, L.J.; Lanosa, M.; Thorne, A.; Coleman, C.I. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am. J. Clin. Nutr.,  2010, 91(1), 73-81.
[http://dx.doi.org/10.3945/ajcn.2009.28157] [PMID:  19906797] 
[301] 
Yoneshiro, T.; Matsushita, M.; Hibi, M.; Tone, H.; Takeshita, M.; Yasunaga, K.; Katsuragi, Y.; Kameya, T.; Sugie, H.; Saito, M. Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans. Am. J. Clin. Nutr.,  2017, 105(4), 873-881.
[http://dx.doi.org/10.3945/ajcn.116.144972] [PMID:  28275131] 
[302] 
Lee, S.G.; Parks, J.S.; Kang, H.W. Quercetin, a functional compound of onion peel, remodels white adipocytes to brown-like adipocytes. J. Nutr. Biochem.,  2017, 42, 62-71.
[http://dx.doi.org/10.1016/j.jnutbio.2016.12.018] [PMID:  28131896] 
[303] 
Choi, J.H.; Yun, J.W. Chrysin induces brown fat-like phenotype and enhances lipid metabolism in 3T3-L1 adipocytes. Nutrition,  2016, 32(9), 1002-1010.
[http://dx.doi.org/10.1016/j.nut.2016.02.007] [PMID:  27133810] 
[304] 
Zhang, X.; Zhang, Q.X.; Wang, X.; Zhang, L.; Qu, W.; Bao, B.; Liu, C.A.; Liu, J. Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism. Int. J. Obes.,  2016, 40(12), 1841-1849.
[http://dx.doi.org/10.1038/ijo.2016.108] [PMID:  27377953] 
[305] 
Hu, T.; Yuan, X.; Wei, G.; Luo, H.; Lee, H.J.; Jin, W. Myricetin-induced brown adipose tissue activation prevents obesity and insulin resistance in db/db mice. Eur. J. Nutr.,  2018, 57(1), 391-403.
[http://dx.doi.org/10.1007/s00394-017-1433-z] [PMID:  28439667] 
[306] 
Yang, J.Y.; Della-Fera, M.A.; Rayalam, S.; Ambati, S.; Hartzell, D.L.; Park, H.J.; Baile, C.A. Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci.,  2008, 82(19-20), 1032-1039.
[http://dx.doi.org/10.1016/j.lfs.2008.03.003] [PMID:  18433793] 
[307] 
Herranz-López, M.; Borrás-Linares, I.; Olivares-Vicente, M.; Gálvez, J.; Segura-Carretero, A.; Micol, V. Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes. Phytomedicine,  2017, 25, 25-28.
[http://dx.doi.org/10.1016/j.phymed.2016.12.008] [PMID:  28190467] 
[308] 
Lee, C.W.; Seo, J.Y.; Lee, J.; Choi, J.W.; Cho, S.; Bae, J.Y.; Sohng, J.K.; Kim, S.O.; Kim, J.; Park, Y.I. 3-O-Glucosylation of quercetin enhances inhibitory effects on the adipocyte differentiation and lipogenesis. Biomed. Pharmacother.,  2017, 95, 589-598.
[http://dx.doi.org/10.1016/j.biopha.2017.08.002] [PMID:  28869898] 
[309] 
Hsu, C.L.; Yen, G.C. Effects of flavonoids and phenolic acids on the inhibition of adipogenesis in 3T3-L1 adipocytes. J. Agric. Food Chem.,  2007, 55(21), 8404-8410.
[http://dx.doi.org/10.1021/jf071695r] [PMID:  17880164] 
[310] 
Hsu, C.L.; Wu, C.H.; Huang, S.L.; Yen, G.C. Phenolic compounds rutin and o-coumaric acid ameliorate obesity induced by high-fat diet in rats. J. Agric. Food Chem.,  2009, 57(2), 425-431.
[http://dx.doi.org/10.1021/jf802715t] [PMID:  19119847] 
[311] 
Lee, Y.J.; Choi, H.S.; Seo, M.J.; Jeon, H.J.; Kim, K.J.; Lee, B.Y. Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish. Food Funct.,  2015, 6(8), 2824-2833.
[http://dx.doi.org/10.1039/C5FO00481K] [PMID:  26174858] 
[312] 
Wang, S.; Moustaid-Moussa, N.; Chen, L.; Mo, H.; Shastri, A.; Su, R.; Bapat, P.; Kwun, I.; Shen, C.L. Novel insights of dietary polyphenols and obesity. J. Nutr. Biochem.,  2014, 25(1), 1-18.
[http://dx.doi.org/10.1016/j.jnutbio.2013.09.001] [PMID:  24314860] 
[313] 
Xiao, N.; Mei, F.; Sun, Y.; Pan, G.; Liu, B.; Liu, K. Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in adipocytes with regulation of AMP-activated kinase and/or sirtuin 1 activity. Planta Med.,  2014, 80(12), 993-1000.
[http://dx.doi.org/10.1055/s-0034-1382864] [PMID:  25057854] 
[314] 
García-Díaz, J.A.; Navarrete-Vázquez, G.; García-Jiménez, S.; Hidalgo-Figueroa, S.; Almanza-Pérez, J.C.; Alarcón-Aguilar, F.J.; Gómez-Zamudio, J.; Cruz, M.; Ibarra-Barajas, M.; Estrada-Soto, S. Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats. Biomed. Pharmacother.,  2016, 83, 667-675.
[http://dx.doi.org/10.1016/j.biopha.2016.07.023] [PMID:  27470567] 
[315] 
Villar, I.C.; Jiménez, R.; Galisteo, M.; Garcia-Saura, M.F.; Zarzuelo, A.; Duarte, J. Effects of chronic chrysin treatment in spontaneously hypertensive rats. Planta Med.,  2002, 68(9), 847-850.
[http://dx.doi.org/10.1055/s-2002-34400] [PMID:  12357404] 
[316] 
Brown, L.; Poudyal, H.; Panchal, S.K. Functional foods as potential therapeutic options for metabolic syndrome. Obes. Rev.,  2015, 16(11), 914-941.
[http://dx.doi.org/10.1111/obr.12313] [PMID:  26345360] 
[317] 
Chaiittianan, R.; Sutthanut, K.; Rattanathongkom, A. Purple corn silk: A potential anti-obesity agent with inhibition on adipogenesis and induction on lipolysis and apoptosis in adipocytes. J. Ethnopharmacol.,  2017, 201, 9-16.
[http://dx.doi.org/10.1016/j.jep.2017.02.044] [PMID:  28257978] 
[318] 
Yang, C.S.; Zhang, J.; Zhang, L.; Huang, J.; Wang, Y. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea. Mol. Nutr. Food Res.,  2016, 60(1), 160-174.
[http://dx.doi.org/10.1002/mnfr.201500428] [PMID:  26577614] 
[319] 
Janssens, P.L.; Hursel, R.; Westerterp-Plantenga, M.S. Long-term green tea extract supplementation does not affect fat absorption, resting energy expenditure, and body composition in adults. J. Nutr.,  2015, 145(5), 864-870.
[http://dx.doi.org/10.3945/jn.114.207829] [PMID:  25740906] 
[320] 
Dostal, A.M.; Arikawa, A.; Espejo, L.; Kurzer, M.S. Long-term supplementation of green tea extract does not modify adiposity or bone mineral density in a randomized trial of overweight and obese postmenopausal women. J. Nutr.,  2016, 146(2), 256-264.
[http://dx.doi.org/10.3945/jn.115.219238] [PMID:  26701796] 
[321] 
Jurgens, T.M.; Whelan, A.M.; Killian, L.; Doucette, S.; Kirk, S.; Foy, E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database Syst. Rev.,  2012, 12 CD008650
[http://dx.doi.org/10.1002/14651858.CD008650.pub2] [PMID:  23235664] 
[322] 
Mielgo-Ayuso, J.; Barrenechea, L.; Alcorta, P.; Larrarte, E.; Margareto, J.; Labayen, I. Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial. Br. J. Nutr.,  2014, 111(7), 1263-1271.
[http://dx.doi.org/10.1017/S0007114513003784] [PMID:  24299662] 
[323] 
Weir, G.C.; Bonner-Weir, S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes,  2004, 53(Suppl. 3), S16-S21.
[http://dx.doi.org/10.2337/diabetes.53.suppl_3.S16] [PMID:  15561905] 
[324] 
Yang, K.; Gotzmann, J.; Kuny, S.; Huang, H.; Sauvé, Y.; Chan, C.B. Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes. J. Endocrinol.,  2016, 229(3), 343-356.
[http://dx.doi.org/10.1530/JOE-15-0517] [PMID:  27068697] 
[325] 
Faerch, K.; Hulmán, A.; Solomon, T.P. Heterogeneity of pre-diabetes and type 2 diabetes: implications for prediction, prevention and treatment responsiveness. Curr. Diabetes Rev.,  2016, 12(1), 30-41.
[http://dx.doi.org/10.2174/1573399811666150416122903] [PMID:  25877695] 
[326] 
Pecoits-Filho, R.; Abensur, H.; Betônico, C.C.; Machado, A.D.; Parente, E.B.; Queiroz, M.; Salles, J.E.; Titan, S.; Vencio, S. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol. Metab. Syndr.,  2016, 8, 50.
[http://dx.doi.org/10.1186/s13098-016-0159-z] [PMID:  27471550] 
[327] 
Mizokami-Stout, K.; Cree-Green, M.; Nadeau, K.J. Insulin resistance in type 2 diabetic youth. Curr. Opin. Endocrinol. Diabetes Obes.,  2012, 19(4), 255-262.
[http://dx.doi.org/10.1097/MED.0b013e3283557cd5] [PMID:  22732484] 
[328] 
Shirwany, N.A.; Zou, M.H. AMPK: a cellular metabolic and redox sensor. A minireview. Front. Biosci.,  2014, 19, 447-474.
[http://dx.doi.org/10.2741/4218] [PMID:  24389195] 
[329] 
Rutter, G.A.; Da Silva Xavier, G.; Leclerc, I. Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem. J.,  2003, 375(Pt 1), 1-16.
[http://dx.doi.org/10.1042/bj20030048] [PMID:  12839490] 
[330] 
Dhanya, R.; Arya, A.D.; Nisha, P.; Jayamurthy, P. Quercetin, a lead compound against type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front. Pharmacol.,  2017, 8, 336.
[http://dx.doi.org/10.3389/fphar.2017.00336] [PMID:  28642704] 
[331] 
Lin, X.H.; Pan, J.B.; Zhang, X.J. WITHDRAWN: Antiinflammatory
and anti-oxidant effects of apigetrin on LPSinduced
acute lung injury by regulating Nrf2 and AMPK
pathways. Biochem. Biophys. Res. Commun,  2017, S0006-291X(17), 31413-4.
[http://dx.doi.org/10.1016/j.bbrc.2017.07.071] [PMID:  28712867] 
[332] 
Tsai, K.L.; Hung, C.H.; Chan, S.H.; Shih, J.Y.; Cheng, Y.H.; Tsai, Y.J.; Lin, H.C.; Chu, P.M. Baicalein protects against oxLDL-caused oxidative stress and inflammation by modulation of AMPK-alpha. Oncotarget,  2016, 7(45), 72458-72468.
[http://dx.doi.org/10.18632/oncotarget.12788] [PMID:  27776344] 
[333] 
Alkhalidy, H.; Moore, W.; Zhang, Y.; McMillan, R.; Wang, A.; Ali, M.; Suh, K.S.; Zhen, W.; Cheng, Z.; Jia, Z.; Hulver, M.; Liu, D. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic β -cell mass in middle-aged obese diabetic mice. J. Diabetes Res.,  2015, 2015 532984
[http://dx.doi.org/10.1155/2015/532984] [PMID:  26064984] 
[334] 
Liu, X.; Wang, N.; Fan, S.; Zheng, X.; Yang, Y.; Zhu, Y.; Lu, Y.; Chen, Q.; Zhou, H.; Zheng, J. The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway. Sci. Rep.,  2016, 6, 39735.
[http://dx.doi.org/10.1038/srep39735] [PMID:  28004841] 
[335] 
Zeinali, M.; Rezaee, S.A.; Hosseinzadeh, H. An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed. Pharmacother.,  2017, 92, 998-1009.
[http://dx.doi.org/10.1016/j.biopha.2017.06.003] [PMID:  28609844] 
[336] 
Zhang, Z.X.; Li, Y.B.; Zhao, R.P. Epigallocatechin gallate attenuates β-amyloid generation and oxidative stress involvement of PPARγ in N2a/APP695 cells. Neurochem. Res.,  2017, 42(2), 468-480.
[http://dx.doi.org/10.1007/s11064-016-2093-8] [PMID:  27889855] 
[337] 
Jin, Y.G.; Yuan, Y.; Wu, Q.Q.; Zhang, N.; Fan, D.; Che, Y.; Wang, Z.P.; Xiao, Y.; Wang, S.S.; Tang, Q.Z. Puerarin protects against cardiac fibrosis associated with the inhibition of TGF-β1/smad2-mediated endothelial-to-mesenchymal transition. PPAR Res.,  2017, 20172647129
[http://dx.doi.org/10.1155/2017/2647129] [PMID:  28638404] 
[338] 
Xu, N.; Zhang, L.; Dong, J.; Zhang, X.; Chen, Y.G.; Bao, B.; Liu, J. Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice. Mol. Nutr. Food Res.,  2014, 58(6), 1258-1268.
[http://dx.doi.org/10.1002/mnfr.201300830] [PMID:  24668788] 
[339] 
Zhang, L.; Han, Y.J.; Zhang, X.; Wang, X.; Bao, B.; Qu, W.; Liu, J. Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages. Diabetologia,  2016, 59(10), 2219-2228.
[http://dx.doi.org/10.1007/s00125-016-4039-8] [PMID:  27377644] 
[340] 
Zhou, Y.; Wu, Y.; Qin, Y.; Liu, L.; Wan, J.; Zou, L.; Zhang, Q.; Zhu, J.; Mi, M. Ampelopsin improves insulin resistance by activating PPARγ and subsequently up-regulating FGF21-AMPK signaling pathway. PLoS One,  2016, 11(7) e0159191
[http://dx.doi.org/10.1371/journal.pone.0159191] [PMID:  27391974] 
[341] 
Zang, Y.; Zhang, L.; Igarashi, K.; Yu, C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food Funct.,  2015, 6(3), 834-841.
[http://dx.doi.org/10.1039/C4FO00844H] [PMID:  25599885] 
[342] 
Song, Y.; Kim, M.B.; Kim, C.; Kim, J.; Hwang, J.K. 5,7-Dimethoxyflavone attenuates obesity by inhibiting adipogenesis in 3T3-L1 adipocytes and high-fat diet-induced obese C57BL/6J mice. J. Med. Food,  2016, 19(12), 1111-1119.
[http://dx.doi.org/10.1089/jmf.2016.3800] [PMID:  27828718] 
[343] 
Mahmoud, A.M.; Ashour, M.B.; Abdel-Moneim, A.; Ahmed, O.M. Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats. J. Diabetes Complications,  2012, 26(6), 483-490.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.06.001] [PMID:  22809898] 
[344] 
Sharma, A.K.; Bharti, S.; Ojha, S.; Bhatia, J.; Kumar, N.; Ray, R.; Kumari, S.; Arya, D.S. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br. J. Nutr.,  2011, 106(11), 1713-1723.
[http://dx.doi.org/10.1017/S000711451100225X] [PMID:  21736771] 
[345] 
Pu, P.; Wang, X.A.; Salim, M.; Zhu, L.H.; Wang, L.; Chen, K.J.; Xiao, J.F.; Deng, W.; Shi, H.W.; Jiang, H.; Li, H.L. Baicalein, a natural product, selectively activating AMPKα(2) and ameliorates metabolic disorder in diet-induced mice. Mol. Cell. Endocrinol.,  2012, 362(1-2), 128-138.
[http://dx.doi.org/10.1016/j.mce.2012.06.002] [PMID:  22698522] 
[346] 
Li Volti, G.; Salomone, S.; Sorrenti, V.; Mangiameli, A.; Urso, V.; Siarkos, I.; Galvano, F.; Salamone, F. Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc. Diabetol.,  2011, 10, 62.
[http://dx.doi.org/10.1186/1475-2840-10-62] [PMID:  21756303] 
[347] 
Bouderba, S.; Sanchez-Martin, C.; Villanueva, G.R.; Detaille, D.; Koceïr, E.A. Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes. J. Diabetes,  2014, 6(2), 184-192.
[http://dx.doi.org/10.1111/1753-0407.12083] [PMID:  23953934] 
[348] 
Nurdiana, S.; Goh, Y.M.; Ahmad, H.; Dom, S.M.; Syimal’ain Azmi, N.; Noor Mohamad Zin, N.S.; Ebrahimi, M. Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin. BMC Complement. Altern. Med.,  2017, 17(1), 290.
[http://dx.doi.org/10.1186/s12906-017-1762-8] [PMID:  28576138] 
[349] 
Ren, B.; Qin, W.; Wu, F.; Wang, S.; Pan, C.; Wang, L.; Zeng, B.; Ma, S.; Liang, J. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. Eur. J. Pharmacol.,  2016, 773, 13-23.
[http://dx.doi.org/10.1016/j.ejphar.2016.01.002] [PMID:  26801071] 
[350] 
Cremonini, E.; Bettaieb, A.; Haj, F.G.; Fraga, C.G.; Oteiza, P.I. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch. Biochem. Biophys.,  2016, 599, 13-21.
[http://dx.doi.org/10.1016/j.abb.2016.03.006] [PMID:  26968772] 
[351] 
Menezes, R.; Rodriguez-Mateos, A.; Kaltsatou, A.; González-Sarrías, A.; Greyling, A.; Giannaki, C.; Andres-Lacueva, C.; Milenkovic, D.; Gibney, E.R.; Dumont, J.; Schär, M.; Garcia-Aloy, M.; Palma-Duran, S.A.; Ruskovska, T.; Maksimova, V.; Combet, E.; Pinto, P. Impact of flavonols on cardiometabolic biomarkers: a meta-analysis of randomized controlled human trials to explore the role of inter-individual variability. Nutrients,  2017, 9(2)E117
[http://dx.doi.org/10.3390/nu9020117] [PMID:  28208791] 
[352] 
Voroneanu, L.; Nistor, I.; Dumea, R.; Apetrii, M.; Covic, A. Silymarin in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. J. Diabetes Res.,  2016, 2016 5147468
[http://dx.doi.org/10.1155/2016/5147468] [PMID:  27340676] 
[353] 
Rezvan, N.; Moini, A.; Janani, L.; Mohammad, K.; Saedisomeolia, A.; Nourbakhsh, M.; Gorgani-Firuzjaee, S.; Mazaherioun, M.; Hosseinzadeh-Attar, M.J. Effects of quercetin on adiponectin-mediated insulin sensitivity in polycystic ovary syndrome: a randomized placebo-controlled double-blind clinical trial. Horm. Metab. Res.,  2017, 49(2), 115-121.
[http://dx.doi.org/10.1055/s-0042-118705] [PMID:  27824398] 
[354] 
Wang, Z.; Zhai, D.; Zhang, D.; Bai, L.; Yao, R.; Yu, J.; Cheng, W.; Yu, C. Quercetin decreases insulin resistance in a polycystic ovary syndrome rat model by improving inflammatory microenvironment. Reprod. Sci.,  2017, 24(5), 682-690.
[http://dx.doi.org/10.1177/1933719116667218] [PMID:  27634381] 
[355] 
Chen, S.; Zhao, X.; Wan, J.; Ran, L.; Qin, Y.; Wang, X.; Gao, Y.; Shu, F.; Zhang, Y.; Liu, P.; Zhang, Q.; Zhu, J.; Mi, M. Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: A randomized controlled trial. Pharmacol. Res.,  2015, 99, 74-81.
[http://dx.doi.org/10.1016/j.phrs.2015.05.009] [PMID:  26032587] 
[356] 
Shi, Y.; Williamson, G. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial. Br. J. Nutr.,  2016, 115(5), 800-806.
[http://dx.doi.org/10.1017/S0007114515005310] [PMID:  26785820] 
[357] 
Turnbull, F. Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet,  2003, 362(9395), 1527-1535.
[http://dx.doi.org/10.1016/S0140-6736(03)14739-3] [PMID:  14615107] 
[358] 
Schächinger, V.; Britten, M.B.; Zeiher, A.M. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation,  2000, 101(16), 1899-1906.
[http://dx.doi.org/10.1161/01.CIR.101.16.1899] [PMID:  10779454] 
[359] 
Widlansky, M.E.; Gokce, N.; Keaney, J.F. Jr.; Vita, J.A. The clinical implications of endothelial dysfunction. J. Am. Coll. Cardiol.,  2003, 42(7), 1149-1160.
[http://dx.doi.org/10.1016/S0735-1097(03)00994-X] [PMID:  14522472] 
[360] 
Huang, Y.T.; Hwang, J.J.; Lee, P.P.; Ke, F.C.; Huang, J.H.; Huang, C.J.; Kandaswami, C.; Middleton, E., Jr; Lee, M.T. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br. J. Pharmacol.,  1999, 128(5), 999-1010.
[http://dx.doi.org/10.1038/sj.bjp.0702879] [PMID:  10556937] 
[361] 
Motoyama, K.; Koyama, H.; Moriwaki, M.; Emura, K.; Okuyama, S.; Sato, E.; Inoue, M.; Shioi, A.; Nishizawa, Y. Atheroprotective and plaque-stabilizing effects of enzymatically modified isoquercitrin in atherogenic apoE-deficient mice. Nutrition,  2009, 25(4), 421-427.
[http://dx.doi.org/10.1016/j.nut.2008.08.013] [PMID:  19026522] 
[362] 
Ci, Y.; Qiao, J.; Han, M. Molecular mechanisms and metabolomics of natural polyphenols interfering with breast cancer metastasis. Molecules,  2016, 21(12) E1634
[http://dx.doi.org/10.3390/molecules21121634] [PMID:  27999314] 
[363] 
Testai, L. Flavonoids and mitochondrial pharmacology: A new paradigm for cardioprotection. Life Sci.,  2015, 135, 68-76.
[http://dx.doi.org/10.1016/j.lfs.2015.04.017] [PMID:  26006042] 
[364] 
Hertog, M.G.; Feskens, E.J.; Hollman, P.C.; Katan, M.B.; Kromhout, D. Dietary antioxidant flavonoids and risk of coronary heart disease: the zutphen elderly study. Lancet,  1993, 342(8878), 1007-1011.
[http://dx.doi.org/10.1016/0140-6736(93)92876-U] [PMID:  8105262] 
[365] 
Jiang, W.; Wei, H.; He, B. Dietary flavonoids intake and the risk of coronary heart disease: a dose-response meta-analysis of 15 prospective studies. Thromb. Res.,  2015, 135(3), 459-463.
[http://dx.doi.org/10.1016/j.thromres.2014.12.016] [PMID:  25555317] 
[366] 
Cassidy, A.; Bertoia, M.; Chiuve, S.; Flint, A.; Forman, J.; Rimm, E.B. Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men. Am. J. Clin. Nutr.,  2016, 104(3), 587-594.
[http://dx.doi.org/10.3945/ajcn.116.133132] [PMID:  27488237] 
[367] 
Goetz, M.E.; Judd, S.E.; Safford, M.M.; Hartman, T.J.; McClellan, W.M.; Vaccarino, V. Dietary flavonoid intake and incident coronary heart disease: the REasons for geographic and racial differences in stroke (REGARDS) study. Am. J. Clin. Nutr.,  2016, 104(5), 1236-1244.
[http://dx.doi.org/10.3945/ajcn.115.129452] [PMID:  27655439] 
[368] 
Lloyd-Jones, D.; Adams, R.; Carnethon, M.; De Simone, G.; Ferguson, T.B.; Flegal, K.; Ford, E.; Furie, K.; Go, A.; Greenlund, K.; Haase, N.; Hailpern, S.; Ho, M.; Howard, V.; Kissela, B.; Kittner, S.; Lackland, D.; Lisabeth, L.; Marelli, A.; McDermott, M.; Meigs, J.; Mozaffarian, D.; Nichol, G.; O’Donnell, C.; Roger, V.; Rosamond, W.; Sacco, R.; Sorlie, P.; Stafford, R.; Steinberger, J.; Thom, T.; Wasserthiel-Smoller, S.; Wong, N.; Wylie-Rosett, J.; Hong, Y. American heart association statistics committee and stroke statistics subcommittee. heart disease and stroke statistics--2009 update: a report from the american heart association statistics committee and stroke statistics subcommittee. Circulation,  2009, 119(3), 480-486.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.191259] [PMID:  19171871] 
[369] 
Dirnagl, U.; Iadecola, C.; Moskowitz, M.A. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci.,  1999, 22(9), 391-397.
[http://dx.doi.org/10.1016/S0166-2236(99)01401-0] [PMID:  10441299] 
[370] 
Khoshnam, S.E.; Winlow, W.; Farzaneh, M.; Farbood, Y.; Moghaddam, H.F. Pathogenic mechanisms following ischemic stroke. Neurol. Sci.,  2017, 38(7), 1167-1186.
[http://dx.doi.org/10.1007/s10072-017-2938-1] [PMID:  28417216] 
[371] 
Nagy, Z.; Nardai, S. Cerebral ischemia/repefusion injury: From bench space to bedside. Brain Res. Bull.,  2017, 134, 30-37.
[http://dx.doi.org/10.1016/j.brainresbull.2017.06.011] [PMID:  28625785] 
[372] 
Simonyi, A.; Wang, Q.; Miller, R.L.; Yusof, M.; Shelat, P.B.; Sun, A.Y.; Sun, G.Y. Polyphenols in cerebral ischemia: novel targets for neuroprotection. Mol. Neurobiol.,  2005, 31(1-3), 135-147.
[http://dx.doi.org/10.1385/MN:31:1-3:135] [PMID:  15953817] 
[373] 
Curin, Y.; Ritz, M.F.; Andriantsitohaina, R. Cellular mechanisms of the protective effect of polyphenols on the neurovascular unit in strokes. Cardiovasc. Hematol. Agents Med. Chem.,  2006, 4(4), 277-288.
[http://dx.doi.org/10.2174/187152506778520691] [PMID:  17073605] 
[374] 
Silva, B.; Oliveira, P.J.; Dias, A.; Malva, J.O. Quercetin, kaempferol and biapigenin from hypericum perforatum are neuroprotective against excitotoxic insults. Neurotox. Res.,  2008, 13(3-4), 265-279.
[http://dx.doi.org/10.1007/BF03033510] [PMID:  18522906] 
[375] 
Jurkovicova, D.; Kopacek, J.; Stefanik, P.; Kubovcakova, L.; Zahradnikova, A., Jr; Zahradnikova, A.; Pastorekova, S.; Krizanova, O. Hypoxia modulates gene expression of IP3 receptors in rodent cerebellum. Pflugers Arch.,  2007, 454(3), 415-425.
[http://dx.doi.org/10.1007/s00424-007-0214-6] [PMID:  17285299] 
[376] 
Mercer, L.D.; Kelly, B.L.; Horne, M.K.; Beart, P.M. Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem. Pharmacol.,  2005, 69(2), 339-345.
[http://dx.doi.org/10.1016/j.bcp.2004.09.018] [PMID:  15627486] 
[377] 
Echeverry, C.; Arredondo, F.; Abin-Carriquiry, J.A.; Midiwo, J.O.; Ochieng, C.; Kerubo, L.; Dajas, F. Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study. J. Agric. Food Chem.,  2010, 58(4), 2111-2115.
[http://dx.doi.org/10.1021/jf902951v] [PMID:  20095615] 
[378] 
Lee, Y.J.; Bernstock, J.D.; Nagaraja, N.; Ko, B.; Hallenbeck, J.M. Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose. J. Neurochem.,  2016, 138(1), 101-116.
[http://dx.doi.org/10.1111/jnc.13643] [PMID:  27087120] 
[379] 
Shutenko, Z.; Henry, Y.; Pinard, E.; Seylaz, J.; Potier, P.; Berthet, F.; Girard, P.; Sercombe, R. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem. Pharmacol.,  1999, 57(2), 199-208.
[http://dx.doi.org/10.1016/S0006-2952(98)00296-2] [PMID:  9890569] 
[380] 
Cho, J.Y.; Kim, I.S.; Jang, Y.H.; Kim, A.R.; Lee, S.R. Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. Neurosci. Lett.,  2006, 404(3), 330-335.
[http://dx.doi.org/10.1016/j.neulet.2006.06.010] [PMID:  16806698] 
[381] 
Patil, C.S.; Singh, V.P.; Satyanarayan, P.S.; Jain, N.K.; Singh, A.; Kulkarni, S.K. Protective effect of flavonoids against aging- and lipopolysaccharide-induced cognitive impairment in mice. Pharmacology,  2003, 69(2), 59-67.
[http://dx.doi.org/10.1159/000072357] [PMID:  12928578] 
[382] 
Kao, T.K.; Ou, Y.C.; Raung, S.L.; Lai, C.Y.; Liao, S.L.; Chen, C.J. Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci.,  2010, 86(9-10), 315-321.
[http://dx.doi.org/10.1016/j.lfs.2009.12.014] [PMID:  20060843] 
[383] 
Sharma, V.; Mishra, M.; Ghosh, S.; Tewari, R.; Basu, A.; Seth, P.; Sen, E. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain Res. Bull.,  2007, 73(1-3), 55-63.
[http://dx.doi.org/10.1016/j.brainresbull.2007.01.016] [PMID:  17499637] 
[384] 
Jang, J.W.; Lee, J.K.; Hur, H.; Kim, T.W.; Joo, S.P.; Piao, M.S. Rutin improves functional outcome via reducing the elevated matrix metalloproteinase-9 level in a photothrombotic focal ischemic model of rats. J. Neurol. Sci.,  2014, 339(1-2), 75-80.
[http://dx.doi.org/10.1016/j.jns.2014.01.024] [PMID:  24507948] 
[385] 
Xiong, D.; Deng, Y.; Huang, B.; Yin, C.; Liu, B.; Shi, J.; Gong, Q. Icariin attenuates cerebral ischemia-reperfusion injury through inhibition of inflammatory response mediated by NF-κB, PPARα and PPARγ in rats. Int. Immunopharmacol.,  2016, 30, 157-162.
[http://dx.doi.org/10.1016/j.intimp.2015.11.035] [PMID:  26679678] 
[386] 
Sagara, Y.; Vanhnasy, J.; Maher, P. Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation. J. Neurochem.,  2004, 90(5), 1144-1155.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02563.x] [PMID:  15312169] 
[387] 
Zheng, L.T.; Ock, J.; Kwon, B.M.; Suk, K. Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity. Int. Immunopharmacol.,  2008, 8(3), 484-494.
[http://dx.doi.org/10.1016/j.intimp.2007.12.012] [PMID:  18279803] 
[388] 
Gelderblom, M.; Leypoldt, F.; Lewerenz, J.; Birkenmayer, G.; Orozco, D.; Ludewig, P.; Thundyil, J.; Arumugam, T.V.; Gerloff, C.; Tolosa, E.; Maher, P.; Magnus, T. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. J. Cereb. Blood Flow Metab.,  2012, 32(5), 835-843.
[http://dx.doi.org/10.1038/jcbfm.2011.189] [PMID:  22234339] 
[389] 
Xu, M.; Chen, X.; Gu, Y.; Peng, T.; Yang, D.; Chang, R.C.; So, K.F.; Liu, K.; Shen, J. Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury. J. Ethnopharmacol.,  2013, 150(1), 116-124.
[http://dx.doi.org/10.1016/j.jep.2013.08.020] [PMID:  23973788] 
[390] 
Sokolov, A.N.; Pavlova, M.A.; Klosterhalfen, S.; Enck, P. Chocolate and the brain: neurobiological impact of cocoa flavanols on cognition and behavior. Neurosci. Biobehav. Rev.,  2013, 37(10 Pt 2), 2445-2453.
[http://dx.doi.org/10.1016/j.neubiorev.2013.06.013] [PMID:  23810791] 
[391] 
Cheng, T.; Wang, W.; Li, Q.; Han, X.; Xing, J.; Qi, C.; Lan, X.; Wan, J.; Potts, A.; Guan, F.; Wang, J. Cerebroprotection of flavanol (-)-epicatechin after traumatic brain injury via Nrf2-dependent and -independent pathways. Free Radic. Biol. Med.,  2016, 92, 15-28.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.027] [PMID:  26724590] 
[392] 
Shay, J.; Elbaz, H.A.; Lee, I.; Zielske, S.P.; Malek, M.H.; Hüttemann, M. Molecular mechanisms and therapeutic effects of (-)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration. Oxid. Med. Cell. Longev., 2015. 2015181260
[http://dx.doi.org/10.1155/2015/181260] [PMID:  26180580] 
[393] 
Han, J.; Wang, M.; Jing, X.; Shi, H.; Ren, M.; Lou, H. (-)-Epigallocatechin gallate protects against cerebral ischemia-induced oxidative stress via Nrf2/ARE signaling. Neurochem. Res.,  2014, 39(7), 1292-1299.
[http://dx.doi.org/10.1007/s11064-014-1311-5] [PMID:  24792731] 
[394] 
Yao, C.; Zhang, J.; Liu, G.; Chen, F.; Lin, Y. Neuroprotection by (-)-epigallocatechin-3-gallate in a rat model of stroke is mediated through inhibition of endoplasmic reticulum stress. Mol. Med. Rep.,  2014, 9(1), 69-76.
[http://dx.doi.org/10.3892/mmr.2013.1778] [PMID:  24193141] 
[395] 
Lim, S.H.; Kim, H.S.; Kim, Y.K.; Kim, T.M.; Im, S.; Chung, M.E.; Hong, B.Y.; Ko, Y.J.; Kim, H.W.; Lee, J.I. The functional effect of epigallocatechin gallate on ischemic stroke in rats. Acta Neurobiol. Exp. (Warsz.),  2010, 70(1), 40-46.
[http://dx.doi.org/10.1055/s-0042-118705] [PMID:  20407485] 
[396] 
You, Y.P. Epigallocatechin gallate extends the therapeutic window of recombinant tissue plasminogen activator treatment in ischemic rats. J. Stroke Cerebrovasc. Dis.,  2016, 25(4), 990-997.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.01.014] [PMID:  26851971] 
[397] 
Raza, S.S.; Khan, M.M.; Ahmad, A.; Ashafaq, M.; Islam, F.; Wagner, A.P.; Safhi, M.M.; Islam, F. Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke. Neuroscience,  2013, 230, 157-171.
[http://dx.doi.org/10.1016/j.neuroscience.2012.10.041] [PMID:  23103795] 
[398] 
Lan, X.; Wang, W.; Li, Q.; Wang, J. The natural flavonoid pinocembrin: molecular targets and potential therapeutic applications. Mol. Neurobiol.,  2016, 53(3), 1794-1801.
[http://dx.doi.org/10.1007/s12035-015-9125-2] [PMID:  25744566] 
[399] 
Yen, T.L.; Hsu, C.K.; Lu, W.J.; Hsieh, C.Y.; Hsiao, G.; Chou, D.S.; Wu, G.J.; Sheu, J.R. Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats. J. Agric. Food Chem.,  2012, 60(8), 1937-1944.
[http://dx.doi.org/10.1021/jf204909p] [PMID:  22300539] 
[400] 
Dajas, F.; Rivera, F.; Blasina, F.; Arredondo, F.; Echeverry, C.; Lafon, L.; Morquio, A.; Heinzen, H. Cell culture protection and in vivo neuroprotective capacity of flavonoids. Neurotox. Res.,  2003, 5(6), 425-432.
[http://dx.doi.org/10.1007/BF03033172] [PMID:  14715446] 
[401] 
Rivera, F.; Costa, G.; Abin, A.; Urbanavicius, J.; Arruti, C.; Casanova, G.; Dajas, F. Reduction of ischemic brain damage and increase of glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats. Neurotox. Res.,  2008, 13(2), 105-114.
[http://dx.doi.org/10.1007/BF03033562] [PMID:  18515213] 
[402] 
Peterson, J.J.; Dwyer, J.T.; Jacques, P.F.; McCullough, M.L. Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutr. Rev.,  2012, 70(9), 491-508.
[http://dx.doi.org/10.1111/j.1753-4887.2012.00508.x] [PMID:  22946850] 
[403] 
Cassidy, A.; Rimm, E.B.; O’Reilly, E.J.; Logroscino, G.; Kay, C.; Chiuve, S.E.; Rexrode, K.M. Dietary flavonoids and risk of stroke in women. Stroke,  2012, 43(4), 946-951.
[http://dx.doi.org/10.1161/STROKEAHA.111.637835] [PMID:  22363060] 
[404] 
Arab, L.; Khan, F.; Lam, H. Tea consumption and cardiovascular disease risk. Am. J. Clin. Nutr.,  2013, 98(6)(Suppl.), 1651S-1659S.
[http://dx.doi.org/10.3945/ajcn.113.059345] [PMID:  24172310] 
[405] 
Larsson, S.C. Coffee, tea, and cocoa and risk of stroke. Stroke,  2014, 45(1), 309-314.
[http://dx.doi.org/10.1161/STROKEAHA.113.003131] [PMID:  24326448] 
[406] 
Goetz, M.E.; Judd, S.E.; Hartman, T.J.; McClellan, W.; Anderson, A.; Vaccarino, V. Flavanone intake is inversely associated with risk of incident ischemic stroke in the reasons for geographic and racial differences in stroke (REGARDS) study. J. Nutr.,  2016, 146(11), 2233-2243.
[http://dx.doi.org/10.3945/jn.116.230185] [PMID:  27655760] 
[407] 
Patel, R.A.G.; McMullen, P.W. Neuroprotection in the Treatment of Acute Ischemic Stroke. Prog. Cardiovasc. Dis.,  2017, 59(6), 542-548.
[http://dx.doi.org/10.1016/j.pcad.2017.04.005] [PMID:  28465001] 
[408] 
Wang, X.H.; You, Y.P. Epigallocatechin gallate extends therapeutic window of recombinant tissue plasminogen activator treatment for brain ischemic stroke: a randomized double-blind and placebo-controlled trial. Clin. Neuropharmacol.,  2017, 40(1), 24-28.
[http://dx.doi.org/10.1097/WNF.0000000000000197] [PMID:  27941526] 
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DOI https://dx.doi.org/10.2174/0929867326666181220094721	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Cardiovascular Effects of Flavonoids

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