Effects of Green Tea (−)-Epigallocatechin-3-Gallate (EGCG) on Cardiac Function - A Review of the Therapeutic Mechanism and Potentials

Yuejin      Li; Md.   Rezaul   Karim; Buheng      Wang; Jiangnan      Peng
doi:10.2174/1389557522666220328161826
Abstract

Heart disease, the leading cause of death worldwide, refers to various illnesses that affect heart structure and function. Specific abnormalities affecting cardiac muscle contractility and remodeling and common factors including oxidative stress, inflammation, and apoptosis underlie the pathogenesis of heart diseases. Epidemiology studies have associated green tea consumption with lower morbidity and mortality from cardiovascular diseases, including heart and blood vessel dysfunction. Among the various compounds found in green tea, catechins are believed to play a significant role in producing benefits to cardiovascular health. Comprehensive literature reviews have been published to summarize the tea catechins' antioxidative, anti-inflammatory, and anti-apoptosis effects in various diseases, such as cardiovascular diseases, cancers, and metabolic diseases. However, recent studies on tea catechins, especially the most abundant (−)-Epigallocatechin-3-Gallate (EGCG), revealed their capabilities in regulating cardiac muscle contraction by directly altering myofilament Ca²⁺ sensitivity on force development and Ca²⁺ ion handling in cardiomyocytes under both physiological and pathological conditions. In vitro and in vivo data also demonstrated that green tea extract or EGCG protected or rescued cardiac function, independent of their well-known effects against oxidative stress and inflammation. This mini-review will focus on the specific effects of tea catechins on heart muscle contractility at the molecular and cellular level, revisit their effects on oxidative stress and inflammation in various heart diseases, and discuss EGCG's potential as one of the lead compounds for new drug discovery for heart diseases.
Keywords: Green tea, EGCG, heart disease, cardiomyopathy, heart failure, ischemic heart diseases, muscle contractility
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Graphical Abstract

[1] 
Organization, W.H. WHO reveals leading causes of death and disability worldwide:2000-2019; Available from, 2021.  Available from: https://www.who.int/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019
[2] 
Virani, S.S.; Alonso, A.; Aparicio, H.J.; Benjamin, E.J.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Cheng, S.; Delling, F.N.; Elkind, M.S.V.; Evenson, K.R.; Ferguson, J.F.; Gupta, D.K.; Khan, S.S.; Kissela, B.M.; Knutson, K.L.; Lee, C.D.; Lewis, T.T.; Liu, J.; Loop, M.S.; Lutsey, P.L.; Ma, J.; Mackey, J.; Martin, S.S.; Matchar, D.B.; Mussolino, M.E.; Navaneethan, S.D.; Perak, A.M.; Roth, G.A.; Samad, Z.; Satou, G.M.; Schroeder, E.B.; Shah, S.H.; Shay, C.M.; Stokes, A.; VanWagner, L.B.; Wang, N.Y.; Tsao, C.W. Ame-rican heart association council on epidemiology and prevention statistics committee and stroke statistics subcommittee heart disease and stroke statistics-2021 update: A report from the american heart association. Circulation,  2021, 143(8), e254-e743.
[http://dx.doi.org/10.1161/CIR.0000000000000950] [PMID:  33501848] 
[3] 
Prevention, C. f. D. C. a. Underlying Cause of Death 1999-2019. 2020.http://wonder.cdc.gov/ucd-icd10.html
[4] 
Kochman, J.; Jakubczyk, K.; Antoniewicz, J.; Mruk, H.; Janda, K. Health benefits and chemical composition of matcha green tea: A re-view. Molecules,  2020, 26(1), E85.
[http://dx.doi.org/10.3390/molecules26010085] [PMID:  33375458] 
[5] 
Roshanak, S.; Rahimmalek, M.; Goli, S.A. Evaluation of seven different drying treatments in respect to total flavonoid, phenolic, vitamin C content, chlorophyll, antioxidant activity and color of green tea (Camellia sinensis or C. assamica) leaves. J. Food Sci. Technol.,  2016, 53(1), 721-729.
[http://dx.doi.org/10.1007/s13197-015-2030-x] [PMID:  26787992] 
[6] 
Balentine, D.A.; Wiseman, S.A.; Bouwens, L.C. The chemistry of tea flavonoids. Crit. Rev. Food Sci. Nutr.,  1997, 37(8), 693-704.
[http://dx.doi.org/10.1080/10408399709527797] [PMID:  9447270] 
[7] 
Chacko, S.M.; Thambi, P.T.; Kuttan, R.; Nishigaki, I. Beneficial effects of green tea: A literature review. Chin. Med.,  2010, 5(1), 13.
[http://dx.doi.org/10.1186/1749-8546-5-13] [PMID:  20370896] 
[8] 
Shahidi, F. Antioxidants in food and food antioxidants. Nahrung,  2000, 44(3), 158-163.
[http://dx.doi.org/10.1002/1521-3803(20000501)44:3158:AID-FOOD1583.0.CO;2-L] [PMID:  10907235] 
[9] 
Spyracopoulos, L.; Li, M.X.; Sia, S.K.; Gagné, S.M.; Chandra, M.; Solaro, R.J.; Sykes, B.D. Calcium-induced structural transition in the regulatory domain of human cardiac troponin C. Biochemistry,  1997, 36(40), 12138-12146.
[http://dx.doi.org/10.1021/bi971223d] [PMID:  9315850] 
[10] 
Li, M.X.; Spyracopoulos, L.; Sykes, B.D. Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C. Biochemistry,  1999, 38(26), 8289-8298.
[http://dx.doi.org/10.1021/bi9901679] [PMID:  10387074] 
[11] 
Gasmi-Seabrook, G.M.; Howarth, J.W.; Finley, N.; Abusamhadneh, E.; Gaponenko, V.; Brito, R.M.; Solaro, R.J.; Rosevear, P.R. Solution structures of the C-terminal domain of cardiac troponin C free and bound to the N-terminal domain of cardiac troponin I. Biochemistry,  1999, 38(26), 8313-8322.
[http://dx.doi.org/10.1021/bi9902642] [PMID:  10387077] 
[12] 
Mercier, P.; Li, M.X.; Sykes, B.D. Role of the structural domain of troponin C in muscle regulation: NMR studies of Ca2+ binding and subsequent interactions with regions 1-40 and 96-115 of troponin I. Biochemistry,  2000, 39(11), 2902-2911.
[http://dx.doi.org/10.1021/bi992579n] [PMID:  10715110] 
[13] 
Takeda, S.; Yamashita, A.; Maeda, K.; Maéda, Y. Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form. Nature,  2003, 424(6944), 35-41.
[http://dx.doi.org/10.1038/nature01780] [PMID:  12840750] 
[14] 
Papp, Z.; Agostoni, P.; Alvarez, J.; Bettex, D.; Bouchez, S.; Brito, D.; Černý, V.; Comin-Colet, J.; Crespo-Leiro, M.G.; Delgado, J.F.; Édes, I.; Eremenko, A.A.; Farmakis, D.; Fedele, F.; Fonseca, C.; Fruhwald, S.; Girardis, M.; Guarracino, F.; Harjola, V.P.; Heringlake, M.; Her-pain, A.; Heunks, L.M.; Husebye, T.; Ivancan, V.; Karason, K.; Kaul, S.; Kivikko, M.; Kubica, J.; Masip, J.; Matskeplishvili, S.; Mebazaa, A.; Nieminen, M.S.; Oliva, F.; Papp, J.G.; Parissis, J.; Parkhomenko, A.; Põder, P.; Pölzl, G.; Reinecke, A.; Ricksten, S.E.; Riha, H.; Rudi-ger, A.; Sarapohja, T.; Schwinger, R.H.; Toller, W.; Tritapepe, L.; Tschöpe, C.; Wikström, G.; von Lewinski, D.; Vrtovec, B.; Pollesello, P. Levosimendan efficacy and safety: 20 years of SIMDAX in clinical use. Card. Fail. Rev.,  2020, 6, e19.
[http://dx.doi.org/10.15420/cfr.2020.03] [PMID:  32714567] 
[15] 
Robertson, I.M.; Li, M.X.; Sykes, B.D. Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate. J. Biol. Chem.,  2009, 284(34), 23012-23023.
[http://dx.doi.org/10.1074/jbc.M109.021352] [PMID:  19542563] 
[16] 
Friedrich, F.W.; Flenner, F.; Nasib, M.; Eschenhagen, T.; Carrier, L. Epigallocatechin-3-Gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-Targeted knock-in cardiomyopathic mice. Front. Physiol.,  2016, 7, 607.
[http://dx.doi.org/10.3389/fphys.2016.00607] [PMID:  27994558] 
[17] 
Li, Y.; Zhang, L.; Jean-Charles, P.Y.; Nan, C.; Chen, G.; Tian, J.; Jin, J.P.; Gelb, I.J.; Huang, X. Dose-dependent diastolic dysfunction and early death in a mouse model with cardiac troponin mutations. J. Mol. Cell. Cardiol.,  2013, 62, 227-236.
[http://dx.doi.org/10.1016/j.yjmcc.2013.06.007] [PMID:  23810866] 
[18] 
Zhang, L.; Nan, C.; Chen, Y.; Tian, J.; Jean-Charles, P.Y.; Getfield, C.; Wang, X.; Huang, X. Calcium desensitizer catechin reverses diasto-lic dysfunction in mice with restrictive cardiomyopathy. Arch. Biochem. Biophys.,  2015, 573, 69-76.
[http://dx.doi.org/10.1016/j.abb.2015.03.015] [PMID:  25813360] 
[19] 
Frank, K.F.; Bölck, B.; Erdmann, E.; Schwinger, R.H. Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation. Cardiovasc. Res.,  2003, 57(1), 20-27.
[http://dx.doi.org/10.1016/S0008-6363(02)00694-6] [PMID:  12504810] 
[20] 
Lanner, J.T.; Georgiou, D.K.; Joshi, A.D.; Hamilton, S.L. Ryanodine receptors: Structure, expression, molecular details, and function in calcium release. Cold Spring Harb. Perspect. Biol.,  2010, 2(11), a003996.
[http://dx.doi.org/10.1101/cshperspect.a003996] [PMID:  20961976] 
[21] 
Pessah, I.N.; Waterhouse, A.L.; Casida, J.E. The calcium-ryanodine receptor complex of skeletal and cardiac muscle. Biochem. Biophys. Res. Commun.,  1985, 128(1), 449-456.
[http://dx.doi.org/10.1016/0006-291X(85)91699-7] [PMID:  3985981] 
[22] 
Pessah, I.N.; Zimanyi, I. Characterization of multiple [3H]ryanodine binding sites on the Ca2+ release channel of sarcoplasmic reticulum from skeletal and cardiac muscle: Evidence for a sequential mechanism in ryanodine action. Mol. Pharmacol.,  1991, 39(5), 679-689.
[PMID:  1851961] 
[23] 
Feng, W.; Cherednichenko, G.; Ward, C.W.; Padilla, I.T.; Cabrales, E.; Lopez, J.R.; Eltit, J.M.; Allen, P.D.; Pessah, I.N. Green tea catechins are potent sensitizers of ryanodine receptor type 1 (RyR1). Biochem. Pharmacol.,  2010, 80(4), 512-521.
[http://dx.doi.org/10.1016/j.bcp.2010.05.004] [PMID:  20471964] 
[24] 
Feng, W.; Hwang, H.S.; Kryshtal, D.O.; Yang, T.; Padilla, I.T.; Tiwary, A.K.; Puschner, B.; Pessah, I.N.; Knollmann, B.C. Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin. Mol. Pharmacol.,  2012, 82(5), 993-1000.
[http://dx.doi.org/10.1124/mol.112.079707] [PMID:  22918967] 
[25] 
Ishii, T.; Mori, T.; Tanaka, T.; Mizuno, D.; Yamaji, R.; Kumazawa, S.; Nakayama, T.; Akagawa, M. Covalent modification of proteins by green tea polyphenol (-)-epigallocatechin-3-gallate through autoxidation. Free Radic. Biol. Med.,  2008, 45(10), 1384-1394.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.07.023] [PMID:  18771724] 
[26] 
Hajjar, R.J.; Kang, J.X.; Gwathmey, J.K.; Rosenzweig, A. Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum cal-cium ATPase in isolated rat myocytes. Circulation,  1997, 95(2), 423-429.
[http://dx.doi.org/10.1161/01.CIR.95.2.423] [PMID:  9008460] 
[27] 
Hajjar, R.J.; Schmidt, U.; Kang, J.X.; Matsui, T.; Rosenzweig, A. Adenoviral gene transfer of phospholamban in isolated rat cardio-myocytes. Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circ. Res.,  1997, 81(2), 145-153.
[http://dx.doi.org/10.1161/01.RES.81.2.145] [PMID:  9242175] 
[28] 
Angrisano, T.; Schiattarella, G.G.; Keller, S.; Pironti, G.; Florio, E.; Magliulo, F.; Bottino, R.; Pero, R.; Lembo, F.; Avvedimento, E.V.; Esposito, G.; Trimarco, B.; Chiariotti, L.; Perrino, C. Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure. PLoS One,  2014, 9(9), e106024.
[http://dx.doi.org/10.1371/journal.pone.0106024] [PMID:  25181347] 
[29] 
Li, Y.; Yuan, Y.Y.; Meeran, S.M.; Tollefsbol, T.O. Synergistic epigenetic reactivation of estrogen receptor-α (ERα) by combined green tea polyphenol and histone deacetylase inhibitor in ERα-negative breast cancer cells. Mol. Cancer,  2010, 9(1), 274.
[http://dx.doi.org/10.1186/1476-4598-9-274] [PMID:  20946668] 
[30] 
Nandakumar, V.; Vaid, M.; Katiyar, S.K. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis,  2011, 32(4), 537-544.
[http://dx.doi.org/10.1093/carcin/bgq285] [PMID:  21209038] 
[31] 
Thakur, V.S.; Gupta, K.; Gupta, S. Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I his-tone deacetylases. Int. J. Oncol.,  2012, 41(1), 353-361.
[PMID:  22552582] 
[32] 
Liu, L.; Zhao, W.; Liu, J.; Gan, Y.; Liu, L.; Tian, J. Epigallocatechin-3 gallate prevents pressure overload-induced heart failure by up-regulating SERCA2a via histone acetylation modification in mice. PLoS One,  2018, 13(10), e0205123.
[http://dx.doi.org/10.1371/journal.pone.0205123] [PMID:  30286210] 
[33] 
Betteridge, D.J. What is oxidative stress? Metabolism,  2000, 49(2)(Suppl. 1), 3-8.
[http://dx.doi.org/10.1016/S0026-0495(00)80077-3] [PMID:  10693912] 
[34] 
Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev.,  2010, 4(8), 118-126.
[http://dx.doi.org/10.4103/0973-7847.70902] [PMID:  22228951] 
[35] 
Higdon, J.V.; Frei, B. Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions. Crit. Rev. Food Sci. Nutr.,  2003, 43(1), 89-143.
[http://dx.doi.org/10.1080/10408690390826464] [PMID:  12587987] 
[36] 
Zhang, J.; Duan, D.; Song, Z.L.; Liu, T.; Hou, Y.; Fang, J. Small molecules regulating reactive oxygen species homeostasis for cancer the-rapy. Med. Res. Rev.,  2021, 41(1), 342-394.
[http://dx.doi.org/10.1002/med.21734] [PMID:  32981100] 
[37] 
Rice-Evans, C.A.; Miller, N.J.; Paganga, G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic. Biol. Med.,  1996, 20(7), 933-956.
[http://dx.doi.org/10.1016/0891-5849(95)02227-9] [PMID:  8743980] 
[38] 
Kumamoto, M.; Sonda, T.; Nagayama, K.; Tabata, M. Effects of pH and metal ions on antioxidative activities of catechins. Biosci. Biotechnol. Biochem.,  2001, 65(1), 126-132.
[http://dx.doi.org/10.1271/bbb.65.126] [PMID:  11272815] 
[39] 
Lee, K.W.; Lee, H.J.; Lee, C.Y. Antioxidant activity of black tea vs. green tea. J. Nutr.,  2002, 132(4), 785.
[http://dx.doi.org/10.1093/jn/132.4.785] [PMID:  11925478] 
[40] 
Dhalla, N.S.; Temsah, R.M.; Netticadan, T. Role of oxidative stress in cardiovascular diseases. J. Hypertens.,  2000, 18(6), 655-673.
[http://dx.doi.org/10.1097/00004872-200018060-00002] [PMID:  10872549] 
[41] 
Senoner, T.; Dichtl, W. Oxidative stress in cardiovascular diseases: Still a therapeutic target? Nutrients,  2019, 11(9), E2090.
[http://dx.doi.org/10.3390/nu11092090] [PMID:  31487802] 
[42] 
Medzhitov, R. Inflammation 2010: New adventures of an old flame. Cell,  2010, 140(6), 771-776.
[http://dx.doi.org/10.1016/j.cell.2010.03.006] [PMID:  20303867] 
[43] 
Suetomi, T.; Miyamoto, S.; Brown, J.H. Inflammation in nonischemic heart disease: Initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling. Am. J. Physiol. Heart Circ. Physiol.,  2019, 317(5), H877-H890.
[http://dx.doi.org/10.1152/ajpheart.00223.2019] [PMID:  31441689] 
[44] 
Bartekova, M.; Radosinska, J.; Jelemensky, M.; Dhalla, N.S. Role of cytokines and inflammation in heart function during health and disea-se. Heart Fail. Rev.,  2018, 23(5), 733-758.
[http://dx.doi.org/10.1007/s10741-018-9716-x] [PMID:  29862462] 
[45] 
Janczewski, A.M.; Kadokami, T.; Lemster, B.; Frye, C.S.; McTiernan, C.F.; Feldman, A.M. Morphological and functional changes in car-diac myocytes isolated from mice overexpressing TNF-alpha. Am. J. Physiol. Heart Circ. Physiol.,  2003, 284(3), H960-H969.
[http://dx.doi.org/10.1152/ajpheart.0718.2001] [PMID:  12578819] 
[46] 
Dibbs, Z.I.; Diwan, A.; Nemoto, S.; DeFreitas, G.; Abdellatif, M.; Carabello, B.A.; Spinale, F.G.; Feuerstein, G.; Sivasubramanian, N.; Mann, D.L. Targeted overexpression of transmembrane tumor necrosis factor provokes a concentric cardiac hypertrophic phenotype. Circulation,  2003, 108(8), 1002-1008.
[http://dx.doi.org/10.1161/01.CIR.0000085203.46621.F4] [PMID:  12912811] 
[47] 
Fang, L.; Ellims, A.H.; Beale, A.L.; Taylor, A.J.; Murphy, A.; Dart, A.M. Systemic inflammation is associated with myocardial fibrosis, diastolic dysfunction, and cardiac hypertrophy in patients with hypertrophic cardiomyopathy. Am. J. Transl. Res.,  2017, 9(11), 5063-5073.
[PMID:  29218105] 
[48] 
Eskandari, V.; Amirzargar, A.A.; Mahmoudi, M.J.; Rahnemoon, Z.; Rahmani, F.; Sadati, S.; Rahmati, Z.; Gorzin, F.; Hedayat, M.; Rezaei, N. Gene expression and levels of IL-6 and TNFα in PBMCs correlate with severity and functional class in patients with chronic heart fai-lure. Ir. J. Med. Sci.,  2018, 187(2), 359-368.
[http://dx.doi.org/10.1007/s11845-017-1680-2] [PMID:  28889349] 
[49] 
Frantz, S.; Hu, K.; Bayer, B.; Gerondakis, S.; Strotmann, J.; Adamek, A.; Ertl, G.; Bauersachs, J.; Frantz, S.; Hu, K.; Bayer, B.; Gerondakis, S.; Strotmann, J.; Adamek, A.; Ertl, G.; Bauersachs, J. Absence of NF-kappaB subunit p50 improves heart failure after myocardial in-farction. FASEB J.,  2006, 20(11), 1918-1920.
[http://dx.doi.org/10.1096/fj.05-5133fje] [PMID:  16837548] 
[50] 
Liu, C.C.; Huang, Y.; Zhang, J.H.; Xu, Y.; Wu, C.H. Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in rats: Role of toll-like receptor 4 and β-arrestin 2. Eur. Rev. Med. Pharmacol. Sci.,  2013, 17(15), 2103-2110.
[PMID:  23884833] 
[51] 
Moss, N.C.; Stansfield, W.E.; Willis, M.S.; Tang, R.H.; Selzman, C.H. IKKbeta inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol.,  2007, 293(4), H2248-H2253.
[http://dx.doi.org/10.1152/ajpheart.00776.2007] [PMID:  17675566] 
[52] 
Pye, J.; Ardeshirpour, F.; McCain, A.; Bellinger, D.A.; Merricks, E.; Adams, J.; Elliott, P.J.; Pien, C.; Fischer, T.H.; Baldwin, A.S., Jr; Ni-chols, T.C. Proteasome inhibition ablates activation of NF-kappa B in myocardial reperfusion and reduces reperfusion injury. Am. J. Physiol. Heart Circ. Physiol.,  2003, 284(3), H919-H926.
[http://dx.doi.org/10.1152/ajpheart.00851.2002] [PMID:  12424098] 
[53] 
Aneja, R.; Hake, P.W.; Burroughs, T.J.; Denenberg, A.G.; Wong, H.R.; Zingarelli, B. Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Mol. Med.,  2004, 10(1-6), 55-62.
[http://dx.doi.org/10.2119/2004-00032.Aneja] [PMID:  15502883] 
[54] 
Han, S.G.; Han, S.S.; Toborek, M.; Hennig, B. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes. Toxicol. Appl. Pharmacol.,  2012, 261(2), 181-188.
[http://dx.doi.org/10.1016/j.taap.2012.03.024] [PMID:  22521609] 
[55] 
Liu, D.; Perkins, J.T.; Hennig, B. EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells. J. Nutr. Biochem.,  2016, 28, 164-170.
[http://dx.doi.org/10.1016/j.jnutbio.2015.10.003] [PMID:  26878794] 
[56] 
Takano, K.; Nakaima, K.; Nitta, M.; Shibata, F.; Nakagawa, H. Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea, on neutrophil chemotaxis in vitro and in vivo. J. Agric. Food Chem.,  2004, 52(14), 4571-4576.
[http://dx.doi.org/10.1021/jf0355194] [PMID:  15237969] 
[57] 
Kawai, K.; Tsuno, N.H.; Kitayama, J.; Okaji, Y.; Yazawa, K.; Asakage, M.; Hori, N.; Watanabe, T.; Takahashi, K.; Nagawa, H. Epigalloca-techin gallate attenuates adhesion and migration of CD8+ T cells by binding to CD11b. J. Allergy Clin. Immunol.,  2004, 113(6), 1211-1217.
[http://dx.doi.org/10.1016/j.jaci.2004.02.044] [PMID:  15208607] 
[58] 
Lee, W.; Min, W.K.; Chun, S.; Lee, Y.W.; Park, H.; Lee, D.H.; Lee, Y.K.; Son, J.E. Long-term effects of green tea ingestion on atheroscle-rotic biological markers in smokers. Clin. Biochem.,  2005, 38(1), 84-87.
[http://dx.doi.org/10.1016/j.clinbiochem.2004.09.024] [PMID:  15607322] 
[59] 
Ridker, P.M.; Rifai, N.; Rose, L.; Buring, J.E.; Cook, N.R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N. Engl. J. Med.,  2002, 347(20), 1557-1565.
[http://dx.doi.org/10.1056/NEJMoa021993] [PMID:  12432042] 
[60] 
Strasser, A.; O’Connor, L.; Dixit, V.M. Apoptosis signaling. Annu. Rev. Biochem.,  2000, 69(1), 217-245.
[http://dx.doi.org/10.1146/annurev.biochem.69.1.217] [PMID:  10966458] 
[61] 
van Empel, V.P.; Bertrand, A.T.; Hofstra, L.; Crijns, H.J.; Doevendans, P.A.; De Windt, L.J. Myocyte apoptosis in heart failure. Cardiovasc. Res.,  2005, 67(1), 21-29.
[http://dx.doi.org/10.1016/j.cardiores.2005.04.012] [PMID:  15896727] 
[62] 
Bennett, M.R. Apoptosis in the cardiovascular system. Heart,  2002, 87(5), 480-487.
[http://dx.doi.org/10.1136/heart.87.5.480] [PMID:  11997428] 
[63] 
Wencker, D.; Chandra, M.; Nguyen, K.; Miao, W.; Garantziotis, S.; Factor, S.M.; Shirani, J.; Armstrong, R.C.; Kitsis, R.N. A mechanistic role for cardiac myocyte apoptosis in heart failure. J. Clin. Invest.,  2003, 111(10), 1497-1504.
[http://dx.doi.org/10.1172/JCI17664] [PMID:  12750399] 
[64] 
Negri, A.; Naponelli, V.; Rizzi, F.; Bettuzzi, S. Molecular targets of epigallocatechin-gallate (EGCG): A special focus on signal transduction and cancer. Nutrients,  2018, 10(12), E1936.
[http://dx.doi.org/10.3390/nu10121936] [PMID:  30563268] 
[65] 
Al Hroob, A.M.; Abukhalil, M.H.; Hussein, O.E.; Mahmoud, A.M. Pathophysiological mechanisms of diabetic cardiomyopathy and the therapeutic potential of epigallocatechin-3-gallate. Biomed. Pharmacother.,  2019, 109, 2155-2172.
[http://dx.doi.org/10.1016/j.biopha.2018.11.086] [PMID:  30551473] 
[66] 
Othman, A.I.; Elkomy, M.M.; El-Missiry, M.A.; Dardor, M. Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the in-trinsic apoptotic pathway in isoproterenol-induced myocardial infarction. Eur. J. Pharmacol.,  2017, 794, 27-36.
[http://dx.doi.org/10.1016/j.ejphar.2016.11.014] [PMID:  27864105] 
[67] 
Roy, A.M.; Baliga, M.S.; Katiyar, S.K. Epigallocatechin-3-gallate induces apoptosis in estrogen receptor-negative human breast carcinoma cells via modulation in protein expression of p53 and Bax and caspase-3 activation. Mol. Cancer Ther.,  2005, 4(1), 81-90.
[PMID:  15657356] 
[68] 
Messer, A.E.; Bayliss, C.R.; El-Mezgueldi, M.; Redwood, C.S.; Ward, D.G.; Leung, M.C.; Papadaki, M.; Dos Remedios, C.; Marston, S.B. Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation. Arch. Biochem. Biophys.,  2016, 601, 113-120.
[http://dx.doi.org/10.1016/j.abb.2016.03.027] [PMID:  27036851] 
[69] 
Warren, C.M.; Karam, C.N.; Wolska, B.M.; Kobayashi, T.; de Tombe, P.P.; Arteaga, G.M.; Bos, J.M.; Ackerman, M.J.; Solaro, R.J. Green tea catechin normalizes the enhanced Ca2+ sensitivity of myofilaments regulated by a hypertrophic cardiomyopathy-associated mutation in human cardiac troponin I (K206I). Circ. Cardiovasc. Genet.,  2015, 8(6), 765-773.
[http://dx.doi.org/10.1161/CIRCGENETICS.115.001234] [PMID:  26553696] 
[70] 
Quan, J.; Jia, Z.; Lv, T.; Zhang, L.; Liu, L.; Pan, B.; Zhu, J.; Gelb, I.J.; Huang, X.; Tian, J. Green tea extract catechin improves cardiac fun-ction in pediatric cardiomyopathy patients with diastolic dysfunction. J. Biomed. Sci.,  2019, 26(1), 32.
[http://dx.doi.org/10.1186/s12929-019-0528-7] [PMID:  31064352] 
[71] 
Cai, Y.; Yu, S.S.; Chen, T.T.; Gao, S.; Geng, B.; Yu, Y.; Ye, J.T.; Liu, P.Q. EGCG inhibits CTGF expression via blocking NF-κB activation in cardiac fibroblast. Phytomedicine,  2013, 20(2), 106-113.
[http://dx.doi.org/10.1016/j.phymed.2012.10.002] [PMID:  23141425] 
[72] 
Cui, Y.; Wang, Y.; Liu, G. Epigallocatechin gallate (EGCG) attenuates myocardial hypertrophy and fibrosis induced by transverse aortic constriction via inhibiting the Akt/mTOR pathway. Pharm. Biol.,  2021, 59(1), 1305-1313.
[http://dx.doi.org/10.1080/13880209.2021.1972124] [PMID:  34607503] 
[73] 
Sheng, R.; Gu, Z.L.; Xie, M.L.; Zhou, W.X.; Guo, C.Y. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats. Acta Pharmacol. Sin.,  2007, 28(2), 191-201.
[http://dx.doi.org/10.1111/j.1745-7254.2007.00495.x] [PMID:  17241521] 
[74] 
Sheng, R.; Gu, Z.L.; Xie, M.L.; Zhou, W.X.; Guo, C.Y. EGCG inhibits proliferation of cardiac fibroblasts in rats with cardiac hypertrophy. Planta Med.,  2009, 75(2), 113-120.
[http://dx.doi.org/10.1055/s-0028-1088387] [PMID:  19096994] 
[75] 
Kristen, A.V.; Lehrke, S.; Buss, S.; Mereles, D.; Steen, H.; Ehlermann, P.; Hardt, S.; Giannitsis, E.; Schreiner, R.; Haberkorn, U.; Schnabel, P.A.; Linke, R.P.; Röcken, C.; Wanker, E.E.; Dengler, T.J.; Altland, K.; Katus, H.A. Green tea halts progression of cardiac transthyretin amyloidosis: An observational report. Clin. Res. Cardiol.,  2012, 101(10), 805-813.
[http://dx.doi.org/10.1007/s00392-012-0463-z] [PMID:  22584381] 
[76] 
aus dem Siepen, F.; Bauer, R.; Aurich, M.; Buss, S.J.; Steen, H.; Altland, K.; Katus, H.A.; Kristen, A.V. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: An observational study. Drug Des. Devel. Ther.,  2015, 9, 6319-6325.
[http://dx.doi.org/10.2147/DDDT.S96893] [PMID:  26673202] 
[77] 
Bieschke, J.; Russ, J.; Friedrich, R.P.; Ehrnhoefer, D.E.; Wobst, H.; Neugebauer, K.; Wanker, E.E. EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc. Natl. Acad. Sci. USA,  2010, 107(17), 7710-7715.
[http://dx.doi.org/10.1073/pnas.0910723107] [PMID:  20385841] 
[78] 
Ehrnhoefer, D.E.; Bieschke, J.; Boeddrich, A.; Herbst, M.; Masino, L.; Lurz, R.; Engemann, S.; Pastore, A.; Wanker, E.E. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol.,  2008, 15(6), 558-566.
[http://dx.doi.org/10.1038/nsmb.1437] [PMID:  18511942] 
[79] 
Ferreira, N.; Cardoso, I.; Domingues, M.R.; Vitorino, R.; Bastos, M.; Bai, G.; Saraiva, M.J.; Almeida, M.R. Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. FEBS Lett.,  2009, 583(22), 3569-3576.
[http://dx.doi.org/10.1016/j.febslet.2009.10.062] [PMID:  19861125] 
[80] 
Mereles, D.; Buss, S.J.; Hardt, S.E.; Hunstein, W.; Katus, H.A. Effects of the main green tea polyphenol epigallocatechin-3-gallate on car-diac involvement in patients with AL amyloidosis. Clin. Res. Cardiol.,  2010, 99(8), 483-490.
[http://dx.doi.org/10.1007/s00392-010-0142-x] [PMID:  20221615] 
[81] 
Libby, P.; Buring, J.E.; Badimon, L.; Hansson, G.K.; Deanfield, J.; Bittencourt, M.S.; Tokgözoğlu, L.; Lewis, E.F. Atherosclerosis. Nat. Rev. Dis. Primers,  2019, 5(1), 56.
[http://dx.doi.org/10.1038/s41572-019-0106-z] [PMID:  31420554] 
[82] 
Miller, Y.I.; Choi, S.H.; Wiesner, P.; Fang, L.; Harkewicz, R.; Hartvigsen, K.; Boullier, A.; Gonen, A.; Diehl, C.J.; Que, X.; Montano, E.; Shaw, P.X.; Tsimikas, S.; Binder, C.J.; Witztum, J.L. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ. Res.,  2011, 108(2), 235-248.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223875] [PMID:  21252151] 
[83] 
Navab, M.; Ananthramaiah, G.M.; Reddy, S.T.; Van Lenten, B.J.; Ansell, B.J.; Fonarow, G.C.; Vahabzadeh, K.; Hama, S.; Hough, G.; Kamranpour, N.; Berliner, J.A.; Lusis, A.J.; Fogelman, A.M. The oxidation hypothesis of atherogenesis: The role of oxidized phospholi-pids and HDL. J. Lipid Res.,  2004, 45(6), 993-1007.
[http://dx.doi.org/10.1194/jlr.R400001-JLR200] [PMID:  15060092] 
[84] 
Tardif, J.C.; McMurray, J.J.; Klug, E.; Small, R.; Schumi, J.; Choi, J.; Cooper, J.; Scott, R.; Lewis, E.F.; L’Allier, P.L.; Pfeffer, M.A. Aggressive reduction of inflammation stops events (ARISE) trial investigators effects of succinobucol (AGI-1067) after an acute coronary syndrome: A randomised, double-blind, placebo-controlled trial. Lancet,  2008, 371(9626), 1761-1768.
[http://dx.doi.org/10.1016/S0140-6736(08)60763-1] [PMID:  18502300] 
[85] 
Ketelhuth, D.F.; Hansson, G.K. Adaptive response of T and B cells in atherosclerosis. Circ. Res.,  2016, 118(4), 668-678.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306427] [PMID:  26892965] 
[86] 
Nus, M.; Mallat, Z. Immune-mediated mechanisms of atherosclerosis and implications for the clinic. Expert Rev. Clin. Immunol.,  2016, 12(11), 1217-1237.
[http://dx.doi.org/10.1080/1744666X.2016.1195686] [PMID:  27253721] 
[87] 
Ramesh, E.; Geraldine, P.; Thomas, P.A. Regulatory effect of epigallocatechin gallate on the expression of C-reactive protein and other inflammatory markers in an experimental model of atherosclerosis. Chem. Biol. Interact.,  2010, 183(1), 125-132.
[http://dx.doi.org/10.1016/j.cbi.2009.09.013] [PMID:  19782057] 
[88] 
Xu, X.; Pan, J.; Zhou, X. Amelioration of lipid profile and level of antioxidant activities by epigallocatechin-gallate in a rat model of athe-rogenesis. Heart Lung Circ.,  2014, 23(12), 1194-1201.
[http://dx.doi.org/10.1016/j.hlc.2014.05.013] [PMID:  25027849] 
[89] 
Cai, Y.; Kurita-Ochiai, T.; Hashizume, T.; Yamamoto, M. Green tea epigallocatechin-3-gallate attenuates porphyromonas gingivalis-induced atherosclerosis. Pathog. Dis.,  2013, 67(1), 76-83.
[http://dx.doi.org/10.1111/2049-632X.12001] [PMID:  23620122] 
[90] 
Miura, Y.; Chiba, T.; Tomita, I.; Koizumi, H.; Miura, S.; Umegaki, K.; Hara, Y.; Ikeda, M.; Tomita, T. Tea catechins prevent the develop-ment of atherosclerosis in apoprotein E-deficient mice. J. Nutr.,  2001, 131(1), 27-32.
[http://dx.doi.org/10.1093/jn/131.1.27] [PMID:  11208934] 
[91] 
Alves Ferreira, M.; Oliveira Gomes, A.P.; Guimarães de Moraes, A.P.; Ferreira Stringhini, M.L.; Mota, J.F.; Siqueira Guedes Coelho, A.; Borges Botelho, P. Green tea extract outperforms metformin in lipid profile and glycaemic control in overweight women: A double-blind, placebo-controlled, randomized trial. Clin. Nutr. ESPEN,  2017, 22, 1-6.
[http://dx.doi.org/10.1016/j.clnesp.2017.08.008] [PMID:  29415825] 
[92] 
Samavat, H.; Newman, A.R.; Wang, R.; Yuan, J.M.; Wu, A.H.; Kurzer, M.S. Effects of green tea catechin extract on serum lipids in post-menopausal women: A randomized, placebo-controlled clinical trial. Am. J. Clin. Nutr.,  2016, 104(6), 1671-1682.
[http://dx.doi.org/10.3945/ajcn.116.137075] [PMID:  27806972] 
[93] 
Widmer, R.J.; Freund, M.A.; Flammer, A.J.; Sexton, J.; Lennon, R.; Romani, A.; Mulinacci, N.; Vinceri, F.F.; Lerman, L.O.; Lerman, A. Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis. Eur. J. Nutr.,  2013, 52(3), 1223-1231.
[http://dx.doi.org/10.1007/s00394-012-0433-2] [PMID:  22872323] 
[94] 
Quezada-Fernández, P.; Trujillo-Quiros, J.; Pascoe-González, S.; Trujillo-Rangel, W.A.; Cardona-Müller, D.; Ramos-Becerra, C.G. Baro-cio-Pantoja, M.; Rodríguez-de la Cerda, M.; Nérida Sánchez-Rodríguez, E.; Cardona-Muñóz, E.G.; García-Benavides, L.; Grover-Páez, F. Effect of green tea extract on arterial stiffness, lipid profile and sRAGE in patients with type 2 diabetes mellitus: A randomised, double-blind, placebo-controlled trial. Int. J. Food Sci. Nutr.,  2019, 70(8), 977-985.
[http://dx.doi.org/10.1080/09637486.2019.1589430] [PMID:  31084381] 
[95] 
Nakamura, K.; Yamagishi, S.; Adachi, H.; Kurita-Nakamura, Y.; Matsui, T.; Yoshida, T.; Imaizumi, T. Serum levels of sRAGE, the solu-ble form of receptor for advanced glycation end products, are associated with inflammatory markers in patients with type 2 diabetes. Mol. Med.,  2007, 13(3-4), 185-189.
[http://dx.doi.org/10.2119/2006-00090.Nakamura] [PMID:  17592553] 
[96] 
Schmidt, A.M.; Stern, D. Atherosclerosis and diabetes: The RAGE connection. Curr. Atheroscler. Rep.,  2000, 2(5), 430-436.
[http://dx.doi.org/10.1007/s11883-000-0082-4] [PMID:  11122775] 
[97] 
Kim, C.J.; Kim, J.M.; Lee, S.R.; Jang, Y.H.; Kim, J.H.; Chun, K.J. Polyphenol (-)-epigallocatechin gallate targeting myocardial reperfusion limits infarct size and improves cardiac function. Korean J. Anesthesiol.,  2010, 58(2), 169-175.
[http://dx.doi.org/10.4097/kjae.2010.58.2.169] [PMID:  20498796] 
[98] 
Song, D.K.; Jang, Y.; Kim, J.H.; Chun, K.J.; Lee, D.; Xu, Z. Polyphenol (-)-epigallocatechin gallate during ischemia limits infarct size via mitochondrial K(ATP) channel activation in isolated rat hearts. J. Korean Med. Sci.,  2010, 25(3), 380-386.
[http://dx.doi.org/10.3346/jkms.2010.25.3.380] [PMID:  20191036] 
[99] 
Tu, Q.; Jiang, Q.; Xu, M.; Jiao, Y.; He, H.; He, S.; Zheng, W. EGCG decreases myocardial infarction in both I/R and MIRI rats through reducing intracellular Ca2+ and increasing TnT levels in cardiomyocytes. Adv. Clin. Exp. Med.,  2021, 30(6), 607-616.
[http://dx.doi.org/10.17219/acem/134021] [PMID:  34018347] 
[100] 
Hsieh, S.R.; Tsai, D.C.; Chen, J.Y.; Tsai, S.W.; Liou, Y.M. Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation. Pflugers Arch.,  2009, 458(4), 631-642.
[http://dx.doi.org/10.1007/s00424-009-0655-1] [PMID:  19263074] 
[101] 
Hsieh, S.R.; Cheng, W.C.; Su, Y.M.; Chiu, C.H.; Liou, Y.M. Molecular targets for anti-oxidative protection of green tea polyphenols against myocardial ischemic injury. Biomedicine (Taipei),  2014, 4(4), 23.
[http://dx.doi.org/10.7603/s40681-014-0023-0] [PMID:  25520936] 
[102] 
Hao, G.; Li, W.; Teo, K.; Wang, X.; Yang, J.; Wang, Y.; Liu, L.; Yusuf, S.; Investigators, I.C.S. INTERHEART china study investigators influence of tea consumption on acute myocardial infarction in China population: The INTERHEART China study. Angiology,  2015, 66(3), 265-270.
[http://dx.doi.org/10.1177/0003319714531849] [PMID:  24755694] 
[103] 
Kishimoto, Y.; Saita, E.; Taguchi, C.; Aoyama, M.; Ikegami, Y.; Ohmori, R.; Kondo, K.; Momiyama, Y. Associations between green tea consumption and coffee consumption and the prevalence of coronary artery disease. J. Nutr. Sci. Vitaminol. (Tokyo),  2020, 66(3), 237-245.
[http://dx.doi.org/10.3177/jnsv.66.237] [PMID:  32612086] 
[104] 
Mukamal, K.J.; Maclure, M.; Muller, J.E.; Sherwood, J.B.; Mittleman, M.A. Tea consumption and mortality after acute myocardial in-farction. Circulation,  2002, 105(21), 2476-2481.
[http://dx.doi.org/10.1161/01.CIR.0000017201.88994.F7] [PMID:  12034652] 
[105] 
Pang, J.; Zhang, Z.; Zheng, T.Z.; Bassig, B.A.; Mao, C.; Liu, X.; Zhu, Y.; Shi, K.; Ge, J.; Yang, Y.J. Dejia-Huang; Bai, M.; Peng, Y. Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis. Int. J. Cardiol.,  2016, 202, 967-974.
[http://dx.doi.org/10.1016/j.ijcard.2014.12.176] [PMID:  26318390] 
[106] 
Pyshchyta, G.; Mukamal, K.J.; Ahnve, S.; Hallqvist, J.; Gémes, K.; Ahlbom, A.; Janszky, I. Tea consumption, incidence and long-term prognosis of a first acute myocardial infarction--the SHEEP study. Clin. Nutr.,  2012, 31(2), 267-272.
[http://dx.doi.org/10.1016/j.clnu.2011.10.011] [PMID:  22075136] 
[107] 
Nakagawa, K.; Miyazawa, T. Absorption and distribution of tea catechin, (-)-epigallocatechin-3-gallate, in the rat. J. Nutr. Sci. Vitaminol. (Tokyo),  1997, 43(6), 679-684.
[http://dx.doi.org/10.3177/jnsv.43.679] [PMID:  9530620] 
[108] 
Nakagawa, K.; Miyazawa, T. Chemiluminescence-high-performance liquid chromatographic determination of tea catechin, (-)-epigallocatechin 3-gallate, at picomole levels in rat and human plasma. Anal. Biochem.,  1997, 248(1), 41-49.
[http://dx.doi.org/10.1006/abio.1997.2098] [PMID:  9177723] 
[109] 
Lee, M.J.; Maliakal, P.; Chen, L.; Meng, X.; Bondoc, F.Y.; Prabhu, S.; Lambert, G.; Mohr, S.; Yang, C.S. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: Formation of different metabolites and individual variability. Cancer Epidemiol. Biomarkers Prev.,  2002, 11(10 Pt 1), 1025-1032.
[PMID:  12376503] 
[110] 
Meng, X.; Sang, S.; Zhu, N.; Lu, H.; Sheng, S.; Lee, M.J.; Ho, C.T.; Yang, C.S. Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem. Res. Toxicol.,  2002, 15(8), 1042-1050.
[http://dx.doi.org/10.1021/tx010184a] [PMID:  12184788] 
[111] 
Kohri, T.; Matsumoto, N.; Yamakawa, M.; Suzuki, M.; Nanjo, F.; Hara, Y.; Oku, N. Metabolic fate of (-)-[4-(3)H]epigallocatechin gallate in rats after oral administration. J. Agric. Food Chem.,  2001, 49(8), 4102-4112.
[http://dx.doi.org/10.1021/jf001491+] [PMID:  11513717] 
[112] 
Takagaki, A.; Nanjo, F. Metabolism of (-)-epigallocatechin gallate by rat intestinal flora. J. Agric. Food Chem.,  2010, 58(2), 1313-1321.
[http://dx.doi.org/10.1021/jf903375s] [PMID:  20043675] 
[113] 
Chen, W.W.; Qin, G.Y.; Zhang, T.; Feng, W.Y. In vitro drug metabolism of green tea catechins in human, monkey, dog, rat and mouse hepatocytes. Drug Metab. Lett.,  2012, 6(2), 73-93.
[http://dx.doi.org/10.2174/1872312811206020073] [PMID:  22594564] 
[114] 
Swezey, R.R.; Aldridge, D.E.; LeValley, S.E.; Crowell, J.A.; Hara, Y.; Green, C.E. Absorption, tissue distribution and elimination of 4-[(3)h]-epigallocatechin gallate in beagle dogs. Int. J. Toxicol.,  2003, 22(3), 187-193.
[http://dx.doi.org/10.1080/10915810305101] [PMID:  12851151] 
[115] 
Kohri, T.; Nanjo, F.; Suzuki, M.; Seto, R.; Matsumoto, N.; Yamakawa, M.; Hojo, H.; Hara, Y.; Desai, D.; Amin, S.; Conaway, C.C.; Chung, F.L. Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration. J. Agric. Food Chem.,  2001, 49(2), 1042-1048.
[http://dx.doi.org/10.1021/jf0011236] [PMID:  11262069] 
[116] 
Mereles, D.; Hunstein, W. Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises? Int. J. Mol. Sci.,  2011, 12(9), 5592-5603.
[http://dx.doi.org/10.3390/ijms12095592] [PMID:  22016611] 
[117] 
Chen, L.; Lee, M.J.; Li, H.; Yang, C.S. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab. Dispos.,  1997, 25(9), 1045-1050.
[PMID:  9311619] 
[118] 
Peter, B.; Bosze, S.; Horvath, R. Biophysical characteristics of proteins and living cells exposed to the green tea polyphenol epigallocate-chin-3-gallate (EGCg): Review of recent advances from molecular mechanisms to nanomedicine and clinical trials. Eur. Biophys. J.,  2017, 46(1), 1-24.
[http://dx.doi.org/10.1007/s00249-016-1141-2] [PMID:  27313063] 
[119] 
Li, F.; Wang, Y.; Li, D.; Chen, Y.; Qiao, X.; Fardous, R.; Lewandowski, A.; Liu, J.; Chan, T.H.; Dou, Q.P. Perspectives on the recent deve-lopments with green tea polyphenols in drug discovery. Expert Opin. Drug Discov.,  2018, 13(7), 643-660.
[PMID:  29688074] 
[120] 
Lambert, J.D.; Sang, S.; Hong, J.; Kwon, S.J.; Lee, M.J.; Ho, C.T.; Yang, C.S. Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate. Drug Metab. Dispos.,  2006, 34(12), 2111-2116.
[http://dx.doi.org/10.1124/dmd.106.011460] [PMID:  16997910] 
[121] 
Wang, C.C.; Xu, H.; Man, G.C.; Zhang, T.; Chu, K.O.; Chu, C.Y.; Cheng, J.T.; Li, G.; He, Y.X.; Qin, L.; Lau, T.S.; Kwong, J.; Chan, T.H. Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice. Angiogenesis,  2013, 16(1), 59-69.
[http://dx.doi.org/10.1007/s10456-012-9299-4] [PMID:  22948799] 
[122] 
Granja, A.; Frias, I.; Neves, A.R.; Pinheiro, M.; Reis, S. Therapeutic potential of epigallocatechin gallate nanodelivery systems. BioMed Res. Int.,  2017, 2017, 5813793.
[http://dx.doi.org/10.1155/2017/5813793] [PMID:  28791306] 
[123] 
Jiang, Y.; Jiang, Z.; Ma, L.; Huang, Q. Advances in nanodelivery of green tea catechins to enhance the anticancer activity. Molecules,  2021, 26(11), 3301.
[124] 
Rohde, J.; Jacobsen, C.; Kromann-Andersen, H. [Toxic hepatitis triggered by green tea] Ugeskr. Laeger,  2011, 173(3), 205-206.
[PMID:  21241631] 
[125] 
Mazzanti, G.; Menniti-Ippolito, F.; Moro, P.A.; Cassetti, F.; Raschetti, R.; Santuccio, C.; Mastrangelo, S. Hepatotoxicity from green tea: A review of the literature and two unpublished cases. Eur. J. Clin. Pharmacol.,  2009, 65(4), 331-341.
[http://dx.doi.org/10.1007/s00228-008-0610-7] [PMID:  19198822] 
[126] 
Isbrucker, R.A.; Edwards, J.A.; Wolz, E.; Davidovich, A.; Bausch, J. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: Dermal, acute and short-term toxicity studies. Food Chem. Toxicol.,  2006, 44(5), 636-650.
[http://dx.doi.org/10.1016/j.fct.2005.11.003] [PMID:  16387402] 
[127] 
Lambert, J.D.; Kennett, M.J.; Sang, S.; Reuhl, K.R.; Ju, J.; Yang, C.S. Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mi-ce. Food Chem. Toxicol.,  2010, 48(1), 409-416.
[http://dx.doi.org/10.1016/j.fct.2009.10.030] [PMID:  19883714] 
[128] 
Younes, M.; Aggett, P.; Aguilar, F.; Crebelli, R.; Dusemund, B.; Filipič, M.; Frutos, M.J.; Galtier, P.; Gott, D.; Gundert-Remy, U.; Lambré, C.; Leblanc, J.C.; Lillegaard, I.T.; Moldeus, P.; Mortensen, A.; Oskarsson, A.; Stankovic, I.; Waalkens-Berendsen, I.; Woutersen, R.A.; Andrade, R.J.; Fortes, C.; Mosesso, P.; Restani, P.; Arcella, D.; Pizzo, F.; Smeraldi, C.; Wright, M. EFSA Panel on food additives and nu-trient sources added to food (ANS) Scientific opinion on the safety of green tea catechins. EFSA J.,  2018, 16(4), e05239.
[PMID:  32625874] 
[129] 
Rasheed, N.O.; Ahmed, L.A.; Abdallah, D.M.; El-Sayeh, B.M. Nephro-toxic effects of intraperitoneally injected EGCG in diabetic mice: Involvement of oxidative stress, inflammation and apoptosis. Sci. Rep.,  2017, 7(1), 40617.
[http://dx.doi.org/10.1038/srep40617] [PMID:  28098182] 
[130] 
Sergi, C.M. Epigallocatechin-3-Gallate toxicity in children: A potential and current toxicological event in the differential diagnosis with virus-triggered fulminant hepatic failure. Front. Pharmacol.,  2020, 10, 1563.
[http://dx.doi.org/10.3389/fphar.2019.01563] [PMID:  32063842] 
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DOI https://dx.doi.org/10.2174/1389557522666220328161826	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607
Mini-Reviews in Medicinal Chemistry

Effects of Green Tea (−)-Epigallocatechin-3-Gallate (EGCG) on Cardiac Function - A Review of the Therapeutic Mechanism and Potentials

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