Green tea and metabolic syndrome: A 10-year research update review

Document Type : Review Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Metabolic syndrome (MetS) has turned into a prevalent condition that has imposed a tremendous financial strain on public health care systems. It is believed that the MetS consists of four main factors (hypertension, dyslipidemia, hyperglycemia, and obesity) and may lead to cardiovascular events. Camellia sinesis, in the form of green tea (GT), is one of the most consuming beverages worldwide. Catechins are the dominant component of green tea leaves. Epigallocatechin gallate has the maximum potency. GT has been widely used as a supplement in various health conditions. As the oxidative stress pathway is one of the probable mechanisms of MetS etiologies and GT beneficial effects, GT may be a novel strategy to overcome the MetS. This review aims to reveal the probable pharmacological effects of GT on MetS. The last 10-year original articles on MetS parameters and GT have been gathered in this review. This manuscript has summarized the probable effects of green tea and its catechins on MetS and focused on each different aspect of MetS separately, which can be used as a basis for further investigations for introducing effective compounds as a way to interfere with MetS.
It seems that GT can reduce MetS parameters commonly via anti-inflammatory and anti-oxidative mechanisms. Further clinical trials are needed to confirm the use of GT and its constituents for the treatment of MetS.

Keywords


1. McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol 2018; 36:14-20.
2. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37:1595-1607.
3. Grundy SM. Metabolic syndrome update. Trends in Cardiovascular Medicine 2016; 26:364-373.
4. Akaberi M, Hosseinzadeh H. Grapes (Vitis vinifera) as a potential candidate for the therapy of the metabolic syndrome. Phytother Res 2016; 30:540-556.
5. Dehghani S, Mehri S, Hosseinzadeh H. The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review. Iran J Basic Med Sci 2019; 22:460-468.
6. Hassani FV, Shirani K, Hosseinzadeh H. Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: A review. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:931-949.
7. Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest 2015; 38:1147-1157.
8. Razavi BM, Hosseinzadeh H. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 2014; 37:1031-1040.
9. Razavi BM, Hosseinzadeh H. Chapter 34 - a review of the effects of Citrus paradisi (grapefruit) and its flavonoids, naringin, and naringenin in metabolic syndrome. In: Watson RR, Preedy VR, editors. Bioactive food as dietary interventions for diabetes (second edition): Academic Press; 2019. p. 515-543.
10. Sanati S, Razavi BM, Hosseinzadeh H. A review of the effects of Capsicum annuum L. and its constituent, capsaicin, in metabolic syndrome. Iran J Basic Med Sci 2018; 21:439-448.
11. Shakib Z, Shahraki N, Razavi BM, Hosseinzadeh H. Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review. Phytother Res 2019:1– 12.
12. Tabeshpour J, Imenshahidi M, Hosseinzadeh H. A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci 2017; 20:557-568.
13. Tabeshpour J, Razavi BM, Hosseinzadeh H. Effects of avocado (Persea americana) on metabolic syndrome: A comprehensive systematic review. Phytother Res 2017; 31:819-837.
14. Tajmohammadi A, Razavi BM, Hosseinzadeh H. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review. Phytother Res 2018; 32:1933-1949.
15. Tousian Shandiz H, Razavi BM, Hosseinzadeh H. Review of Garcinia mangostana and its xanthones in metabolic syndrome and related complications. Phytother Res 2017; 31:1173-1182.
16. Razavi BM, Hosseinzadeh H. Saffron: A promising natural medicine in the treatment of metabolic syndrome. J Sci Food Agric 2017; 97:1679-1685.
17. Mollazadeh H, Hosseinzadeh H. Cinnamon effects on metabolic syndrome: a review based on its mechanisms. Iran J Basic Med Sci 2016; 19:1258-1270.
18. Hosseinzadeh H, Nassiri-Asl M. Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J Endocrinol Invest 2014; 37:783-788.
19. Alappat B, Sarna JA, Truong C. Anticancer and anti-oxidant properties of flavored green tea extracts. J Agric Life Sci 2015; 2:15-24.
20. Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: A literature review. Chin Med 2010; 5:13-13.
21. Afzal M, Safer AM, Menon M. Green tea polyphenols and their potential role in health and disease. Inflammopharmacology 2015; 23:151-161.
22. Ohishi T, Goto S, Monira P, Isemura M, Nakamura Y. Anti-inflammatory action of green tea. Antiinflamm Antiallergy Agents Med Chem 2016; 15:74-90.
23. Maiti S, Nazmeen A, Medda N, Patra R, Ghosh TK. Flavonoids green tea against oxidant stress and inflammation with related human diseases. Clin Nutr Exp 2019; 24:1-14.
24. Huang J, Wang Y, Xie Z, Zhou Y, Zhang Y, Wan X. The anti-obesity effects of green tea in human intervention and basic molecular studies. Eur J Clin Nutr 2014; 68:1075-1087.
25. Bogdanski P, Suliburska J, Szulinska M, Stepien M, Pupek-Musialik D, Jablecka A. Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutr Res 2012; 32:421-427.
26. Batista Gde A, Cunha CL, Scartezini M, von der Heyde R, Bitencourt MG, Melo SF. Prospective double-blind crossover study of Camellia sinensis (green tea) in dyslipidemias. Arq Bras Cardiol 2009; 93:128-134.
27. Bornhoeft J, Castaneda D, Nemoseck T, Wang P, Henning SM, Hong MY. The protective effects of green tea polyphenols: lipid profile, inflammation, and antioxidant capacity in rats fed an atherogenic diet and dextran sodium sulfate. J Med Food 2012; 15:726-732.
28. Miyata Y, Shida Y, Hakariya T, Sakai H. Anti-Cancer effects of green tea polyphenols against prostate cancer. Molecules 2019; 24:19.
29. Butt MS, Ahmad RS, Sultan MT, Qayyum MM, Naz A. Green tea and anticancer perspectives: Updates from last decade. Crit Rev Food Sci Nutr 2015; 55:792-805.
30. Pervin M, Unno K, Ohishi T, Tanabe H, Miyoshi N, Nakamura Y. Beneficial effects of green tea catechins on neurodegenerative diseases. Molecules 2018; 23:1297.
31. Esmaeelpanah E, Razavi BM, Vahdati Hasani F, Hosseinzadeh H. Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells. Drug Chem Toxicol 2018; 41:441-448.
32. Esmaeelpanah E, Rahmatkhah A, Poormahmood N, Razavi BM, Vahdati Hassani F, Hosseinzadeh H. Protective effect of green tea aqueous extract on acrylamide induced neurotoxicity. Jundishapur J Nat Pharm Prod 2015; 10:e18406.
33. Fazly Bazzaz BS, Sarabandi S, Khameneh B, Hosseinzadeh H. Effect of catechins, green tea extract and methylxanthines in combination with gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa: - Combination therapy against resistant bacteria. J pharmacopuncture 2016; 19:312-318.
34. Rameshrad M, Razavi BM, Hosseinzadeh H. Protective effects of green tea and its main constituents against natural and chemical toxins: A comprehensive review. Food Chem Toxicol 2017; 100:115-137.
35. Saeki K, Hayakawa S, Nakano S, Ito S, Oishi Y, Suzuki Y, et al. In vitro and in silico studies of the molecular interactions of epigallocatechin-3-o-gallate (egcg) with proteins that explain the health benefits of green tea. Molecules 2018; 23:1295.
36. Saboya PP, Bodanese LC, Zimmermann PR, Gustavo AdS, Assumpção CM, Londero F. Metabolic syndrome and quality of life: A systematic review. Revista latino-americana de enfermagem 2016; 24:e2848-e2848.
37. Razavi BM, Lookian F, Hosseinzadeh H. Protective effects of green tea on olanzapine-induced-metabolic syndrome in rats. Biomed Pharmacother 2017; 92:726-731.
38. Chen YK, Cheung C, Reuhl KR, Liu AB, Lee MJ, Lu YP, et al. Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice. J Agric Food Chem 2011; 59:11862-11871.
39. Nugroho DA, Lukitasari M, Rohman MS. Green tea extract improved blood pressure and metabolic profile of metabolic syndrome rat model. J Hypertens 2017; 35:E13-E13.
40. Nugroho DA, Lukitasari M, Rohman MS. Dose-dependent effects of green tea extract on adiponectin level and adiponectin receptor gene expression in metabolic syndrome rat models. J Hypertens 2018; 36:E9-E9.
41. Lukitasari M, Nugroho DA, Rohman MS. Green tea extract administration had a beneficial effect on ppar alpha and ppar gamma gene expression in metabolic syndrome rat model. J Hypertens 2018; 36:E9-E9.
42. Yousaf S, Butt MS, Suleria HA, Iqbal MJ. The role of green tea extract and powder in mitigating metabolic syndromes with special reference to hyperglycemia and hypercholesterolemia. Food Funct 2014; 5:545-556.
43. Basu A, Du M, Sanchez K, Leyva MJ, Betts NM, Blevins S, et al. Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome. Nutrition 2011; 27:206-213.
44. Basu A, Sanchez K, Leyva MJ, Wu MY, Betts NM, Aston CE, et al. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J Am Coll Nutr 2010; 29:31-40.
45. Mortazavi F, Paknahad Z, Hasanzadeh A. Effect of green tea consumption on the metabolic syndrome indices in women: A clinical trial study. Nutr Food Sci 2019; 49:32-46.
46. Vieira Senger AE, Schwanke CH, Gomes I, Valle Gottlieb MG. Effect of green tea (Camellia sinensis) consumption on the components of metabolic syndrome in elderly. J Nutr Health Aging 2012; 16:738-742.
47. Basu A, Betts NM, Mulugeta A, Tong C, Newman E, Lyons TJ. Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome. Nutr Res 2013; 33:180-187.
48. Kim E, Lee M, Kim SS, Kim JH, Jeon YK, Kim BH, et al. Green tea but not coffee consumption is inversely associated with metabolic syndrome; An epidemiological study in Korean adults. Diabetes Res Clin Prac 2016; 120:S85-S85.
49. Morrison M, van der Heijden R, Heeringa P, Kaijzel E, Verschuren L, Blomhoff R, et al. Epicatechin attenuates atherosclerosis and exerts anti-inflammatory effects on diet induced human-crp and nfkb in vivo. Atherosclerosis 2014; 235:E142-E143.
50. Ramesh E, Jayakumar T, Elanchezhian R, Sakthivel M, Geraldine P, Thomas PA. Green tea catechins, alleviate hepatic lipidemic-oxidative injury in Wistar rats fed an atherogenic diet. Chem Biol Interact 2009; 180:10-19.
51. Ramesh E, Geraldine P, Thomas PA. 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; 183:125-132.
52. Miltonprabu S, Thangapandiyan S. Epigallocatechin gallate potentially attenuates Fluoride induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. J Trace Elem Med Biol 2015; 29:321-335.
53. Wang W, Zhang ZZ, Wu Y, Wang RQ, Chen JW, Chen J, et al. (-)-Epigallocatechin-3-Gallate ameliorates atherosclerosis and modulates hepatic lipid metabolic gene expression in apolipoprotein e knockout mice: Involvement of TTC39B. Front Pharmacol 2018; 9:195.
54. Cai Y, Kurita-Ochiai T, Hashizume T, Yamamoto M. Green tea epigallocatechin-3-gallate attenuates Porphyromonas gingivalis-induced atherosclerosis. Pathog Dis 2013; 67:76-83.
55. Ding S, Jiang J, Yu P, Zhang G, Zhang G, Liu X. Green tea polyphenol treatment attenuates atherosclerosis in high-fat diet-fed apolipoprotein E-knockout mice via alleviating dyslipidemia and up-regulating autophagy. PLoS One 2017; 12:e0181666.
56. Minatti J, Wazlawik E, Hort MA, Zaleski FL, Ribeiro-do-Valle RM, Maraschin M, et al. Green tea extract reverses endothelial dysfunction and reduces atherosclerosis progression in homozygous knockout low-density lipoprotein receptor mice. Nutr Res 2012; 32:684-693.
57. Gutierrez-Salmean G, Meaney E, Lanaspa MA, Cicerchi C, Johnson RJ, Dugar S, et al. A randomized, placebo-controlled, double-blind study on the effects of (-)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects. Int J Cardiol 2016; 223:500-506.
58. Gutiérrez-Salmeán G, Ortiz-Vilchis P, Vacaseydel CM, Rubio-Gayosso I, Meaney E, Villarreal F, et al. Acute effects of an oral supplement of (-)-epicatechin on postprandial fat and carbohydrate metabolism in normal and overweight subjects. Food Func 2014; 5:521-527.
59. Huang LH, Liu CY, Wang LY, Huang CJ, Hsu CH. Effects of green tea extract on overweight and obese women with high levels of low density-lipoprotein-cholesterol (LDL-C): a randomised, double-blind, and cross-over placebo-controlled clinical trial. BMC Complement Altern Med 2018; 18:294.
60. Alves Ferreira M, Oliveira Gomes AP, Guimaraes de Moraes AP, Ferreira Stringhini ML, Mota JF, Siqueira Guedes Coelho A, et al. 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.
61. Liu CY, Huang CJ, Huang LH, Chen IJ, Chiu JP, Hsu CH. Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: A randomized, double-blinded, and placebo-controlled trial. Plos One 2014; 9:e91163.
62. Lu CW, Zhu WB, Shen CL, Gao WM. Green tea polyphenols reduce body weight in rats by modulating obesity-related genes. Plos One 2012; 7: e38332.
63. Zhang XZ, Guan J, Cai SL, Du Q, Guo ML. Polymeric in situ hydrogel implant of epigallocatechin gallate (EGCG) for prolonged and improved antihyperlipidemic and anti-obesity activity: Preparation and characterization. J Biomater Tissue Eng 2015; 5:813-817.
64. Cichello SA, Begg DP, Jois M, Weisinger RS. Prevention of diet-induced obesity in C57BL/BJ mice with addition of 2 % dietary green tea but not with cocoa or coffee to a high-fat diet. Med J Nutrition Metab 2013; 6:233-238.
65. Byun JK, Yoon BY, Jhun JY, Oh HJ, Kim EK, Min JK, et al. Epigallocatechin-3-gallate ameliorates both obesity and autoinflammatory arthritis aggravated by obesity by altering the balance among CD4(+) T-cell subsets. Immunol Lett 2014; 157:51-59.
66. Bitzer ZT, Elias RJ, Vijay-Kumar M, Lambert JD. (-)-Epigallocatechin-3-gallate decreases colonic inflammation and permeability in a mouse model of colitis, but reduces macronutrient digestion and exacerbates weight loss. Mol Nutr Food Res 2016; 60:2267-2274.
67. Seo DB, Jeong HW, Cho D, Lee BJ, Lee JH, Choi JY, et al. Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice. J Med Food 2015; 18:549-556.
68. Yan J, Zhao Y, Zhao B. Green tea catechins prevent obesity through modulation of peroxisome proliferator-activated receptors. Sci China Life Sci 2013; 56:804-810.
69. Sampath C, Rashid MR, Sang S, Ahmedna M. Green tea epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity. Biomed Pharmacother 2017; 87:73-81.
70. Rocha A, Bolin AP, Cardoso CA, Otton R. Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity. Eur J Nutr 2016; 55:2231-2244.
71. A Cunha C, Lira F, Rosa J, Pimentel G, Souza G, Silva C, et al. Green tea extract supplementation induces the lipolytic pathway, attenuates obesity, and reduces low-grade inflammation in mice fed a high-fat diet. Mediators Inflamm 2013; 2013:635470.
72. Sogawa M, Seura T, Kohno S, Hirasaka K, Yamaguchi Y, Takagaki R, et al. Awa (Tokushima) lactate-fermented tea as well as green tea enhance the effect of diet restriction on obesity in rats. J Med Invest 2009; 56:42-48.
73. Ahmad RS, Butt MS, Sultan MT, Mushtaq Z, Ahmad S, Dewanjee S, et al. Preventive role of green tea catechins from obesity and related disorders especially hypercholesterolemia and hyperglycemia. J Transl Med 2015; 13:79.
74. Huang JB, Zhang Y, Zhou YB, Zhang ZZ, Xie ZW, Zhang JS, et al. Green tea polyphenols alleviate obesity in broiler chickens through the regulation of lipid-metabolism-related genes and transcription factor expression. J Agric Food Chem 2013; 61:8565-8572.
75. Andre DM, Horimoto CM, Calixto MC, Alexandre EC, Antunes E. Epigallocatechin-3-gallate protects against the exacerbation of allergic eosinophilic inflammation associated with obesity in mice. Int Immunopharmacol 2018; 62:212-219.
76. Guo XJ, Cheng M, Zhang X, Cao JX, Wu ZF, Weng PF. Green tea polyphenols reduce obesity in high-fat diet-induced mice by modulating intestinal microbiota composition. Int J Food Sci Technol 2017; 52:1723-1730.
77. Yamashita S, Hirashima A, Lin IC, Bae J, Nakahara K, Murata M, et al. Saturated fatty acid attenuates anti-obesity effect of green tea. Sci Rep 2018; 8:10023.
78. Ueda M, Ashida H. Green tea prevents obesity by increasing expression of insulin-like growth factor binding protein-1 in adipose tissue of high-fat diet-fed mice. J Agric Food Chem 2012; 60:8917-8923.
79. Sano T, Nagayasu S, Suzuki S, Iwashita M, Yamashita A, Shinjo T, et al. Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance. Nutr Metab Cardiovasc Dis 2017; 27:249-259.
80. Bousova I, Matouskova P, Bartikova H, Szotakova B, Hanusova V, Tomankova V, et al. Influence of diet supplementation with green tea extract on drug-metabolizing enzymes in a mouse model of monosodium glutamate-induced obesity. Eur J Nutr 2016; 55:361-371.
81. Lee LS, Choi JH, Sung MJ, Hur JY, Hur HJ, Park JD, et al. Green tea changes serum and liver metabolomic profiles in mice with high-fat diet-induced obesity. Mol Nutr Food Res 2015; 59:784-794.
82. Zhan W, Liu Y, Li DP, Liu Y. Advancing insights on the anti-obesity biochemical mechanism of (-)-epigallocatechin gallate (EGCG) by inhibiting alpha-amylase activity. Rsc Advances 2016; 6:96918-96927.
83. Thomas J, Thomas G. Effect of catechin rich green tea (Camellia Sinensis) extracts on obesity triggered hepatic steatosis in rats fed with HFCS. Int J Pharma Bio Sci 2013; 4:525-532.
84. Nabi BN, Sedighinejad A, Haghighi M, Farzi F, Rimaz S, Atrkarroushan Z, et al. The anti-obesity effects of green tea: A controlled, randomized, clinical trial. Iran Red Crescent Med J 2018; 20:e55950
85. Levy Y, Narotzki B, Reznick AZ. Green tea, weight loss and physical activity. Clin Nutr 2017; 36:315.
86. Tsai Ch H, Chiu WC, Yang NC, Ouyang CM, Yen YH. A novel green tea meal replacement formula for weight loss among obese individuals: a randomized controlled clinical trial. Int J Food Sci Nutr 2009; 60 Suppl 6:151-159.
87. Gholamreza S, Reza H, Esmailzade A, Alireza BM, Nodoushan IS, Hajian N. Comparison between aerobic exercise and consumption of green tea on weight loss in overweighted men. Sport Sci 2013; 6:44-48.
88. Thielecke F, Rahn G, Bohnke J, Adams F, Birkenfeld A, Jordan J, et al. Epigallocatechin-3-gallate and postprandial fat oxidation in overweight/obese male volunteers: a pilot study. Eur J Clin Nutr 2010; 64:704-713.
89. Josic J, Olsson AT, Wickeberg J, Lindstedt S, Hlebowicz J. Does green tea affect postprandial glucose, insulin and satiety in healthy subjects: A randomized controlled trial. Nutr J 2010; 9:63.
90. Mohammadi S, Hosseinzadeh Attar MJ, Karimi M, Hosseinnezhad A, Eshraghian MR, Hosseini SH, et al. The effects of green tea extract on serum adiponectin concentration and insulin resistance in patients with type 2 diabetes mellitus. J Zanjan Univ Med Sci Health Services 2010; 18:44-57.
91. Mousavi A, Vafa M, Neyestani T, Khamseh M, Hoseini F. The effects of green tea consumption on metabolic and anthropometric indices in patients with Type 2 diabetes. J Res Med Sci 2013; 18:1080-1086.
92. Tehrani HG, Allahdadian M, Zarre F, Ranjbar H, Allahdadian F. Effect of green tea on metabolic and hormonal aspect of polycystic ovarian syndrome in overweight and obese women suffering from polycystic ovarian syndrome: A clinical trial. J Educ Health Promot 2017; 6:36.
93. 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; 111:1263-1271.
94. Soori R, Safei A, Pournemati P, Ghram A. Green tea consumption reduces apelin and orexin-A in overweight and obese women with different training modalities. Sport Sci Health 2018; 14:421-431.
95. Balsan G, Pellanda LC, Sausen G, Galarraga T, Zaffari D, Pontin B, et al. Effect of yerba mate and green tea on paraoxonase and leptin levels in patients affected by overweight or obesity and dyslipidemia: a randomized clinical trial. Nutr J 2019; 18:5.
96. Bettaieb A, Vazquez Prieto MA, Rodriguez Lanzi C, Miatello RM, Haj FG, Fraga CG, et al. (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic Biol Med 2014; 72:247-256.
97. Cremonini E, Bettaieb A, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys 2016; 599:13-21.
98. Liu HW, Chan YC, Wang MF, Wei CC, Chang SJ. Dietary (-)-Epigallocatechin-3-gallate supplementation counteracts aging-associated skeletal muscle insulin resistance and fatty liver in senescence-accelerated mouse. J Agric Food Chem 2015; 63:8407-8417.
99. Yang PX, Li H. Epigallocatechin-3-gallate ameliorates hyperglycemia-induced embryonic vasculopathy and malformation by inhibition of Foxo3a activation. Am J Obstet Gynecol 2010; 203:75.
100. Fang X, Chung J, Olsen E, Snider I, Earls RH, Jeon J, et al. Depletion of regulator-of-G-protein signaling-10 in mice exaggerates high-fat diet-induced insulin resistance and inflammation, and this effect is mitigated by dietary green tea extract. Nutr Res 2019; 70:50-59.
101. Jang HJ, Ridgeway SD, Kim JA. Effects of the green tea polyphenol epigallocatechin-3-gallate on high-fat diet-induced insulin resistance and endothelial dysfunction. Am J Physiol  Endocrinol Metab 2013; 305:E1444-E1451.
102. Otton R, Bolin AP, Ferreira LT, Marinovic MP, Rocha ALS, Mori MA. Polyphenol-rich green tea extract improves adipose tissue metabolism by down-regulating miR-335 expression and mitigating insulin resistance and inflammation. J Nutr Biochem 2018; 57:170-179.
103. Hininger-Favier I, Benaraba R, Coves S, Anderson RA, Roussel AM. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat. J Am Coll Nutr 2009; 28:355-361.
104. Qin BL, Polansky MM, Harry D, Anderson RA. Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats. Mol Nutr Food Res 2010; 54:S14-S23.
105. Roghani M, Baluchnejadmojarad T. Hypoglycemic and hypolipidemic effect and antioxidant activity of chronic epigallocatechin-gallate in streptozotocin-diabetic rats. Pathophysiology 2010; 17:55-59.
106. Yan J, Zhao Y, Suo S, Liu Y, Zhao B. Green tea catechins ameliorate adipose insulin resistance by improving oxidative stress. Free Radic Biol Med 2012; 52:1648-1657.
107. Cremonini E, Wang ZW, Bettaieb A, Adamo AM, Daveri E, Mills DA, et al. (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance. Redox Biol 2018; 14:588-599.
108. Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R. Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Ophthalmic Res 2012; 47:103-108.
109. Fu Z, Yuskavage J, Liu DM. Dietary flavonol epicatechin prevents the onset of type 1 diabetes in nonobese diabetic mice. J Agric Food Chem 2013; 61:4303-4309.
110. Gan L, Meng ZJ, Xiong RB, Guo JQ, Lu XC, Zheng ZW, et al. Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice. Acta Pharmacol Sin 2015; 36:597-605.
111. Zhong J, Xu C, Reece EA, Yang P. The green tea polyphenol EGCG alleviates maternal diabetes–induced neural tube defects by inhibiting DNA hypermethylation. Am J Obstet Gynecol 2016; 215:368.e361-368.e310.
112. Shah T, Shaikh F, Ansari S. To determine the effects of green tea on blood pressure of healthy and type 2 diabetes mellitus (DM) individuals. J Liaquat Univ Med Health Sci 2017; 16:200-204.
113. Lahirin R, Permadhi I, Mudjihartini N, Rahmawati R, Sugianto R. Additional benefit of higher dose green tea in lowering postprandial blood glucose. Med J Indonesia 2015; 24:97-102.
114. Maruyama K, Iso H, Sasaki S, Fukino Y. The association between concentrations of green tea and blood glucose levels. J Clin Biochem Nutr 2009; 44:41-45.
115. Zhang H, Su S, Yu X, Li Y. Dietary epigallocatechin 3-gallate supplement improves maternal and neonatal treatment outcome of gestational diabetes mellitus: a double-blind randomised controlled trial. J Hum Nutr Diet 2017; 30:753-758.
116. Martin BJ, MacInnis MJ, Gillen JB, Skelly LE, Gibala MJ. Short-term green tea extract supplementation attenuates the postprandial blood glucose and insulin response following exercise in overweight men. Appl Physiol Nutr Metab 2016; 41:1057-1063.
117. Huang SM, Chang YH, Chao YC, Lin JA, Wu CH, Lai CY, et al. EGCG-rich green tea extract stimulates sRAGE secretion to inhibit S100A12-RAGE axis through ADAM10-mediated ectodomain shedding of extracellular RAGE in type 2 diabetes. Mol Nutr Food Res 2013; 57:2264-2268.
118. Brown AL, Lane J, Coverly J, Stocks J, Jackson S, Stephen A, et al. Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: Randomized controlled trial. Br J Nutr 2009; 101:886-894.
119. Liu XN, Xu WH, Cai H, Gao YT, Li HL, Ji BT, et al. Green tea consumption and risk of type 2 diabetes in Chinese adults: the Shanghai women’s health study and the shanghai men’s health study. Int J Epidemiol 2018; 47:1887-1896.
120. Toolsee NA, Aruoma OI, Gunness TK, Kowlessur S, Dambala V, Murad F, et al. Effectiveness of green tea in a randomized human cohort: Relevance to diabetes and its complications. Biomed Res Int 2013; 2013:412379-412379
121. Gomez-Guzman M, Jimenez R, Sanchez M, Romero M, O’Valle F, Lopez-Sepulveda R, et al. Chronic (-)-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats. Br J Nutr 2011; 106:1337-1348.
122. Gomez-Guzman M, Jimenez R, Sanchez M, Zarzuelo MJ, Galindo P, Quintela AM, et al. 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; 52:70-79.
123. Jackson D, Connolly K, Batacan R, Ryan K, Vella R, Fenning A. (-)-Epicatechin reduces blood pressure and improves left ventricular function and compliance in deoxycorticosterone acetate-salt hypertensive rats. Molecules 2018; 23:1511.
124. Garcia ML, Pontes RB, Nishi EE, Ibuki FK, Oliveira V, Sawaya ACH, et al. The antioxidant effects of green tea reduces blood pressure and sympathoexcitation in an experimental model of hypertension. J Hypertens 2017; 35:348-354.
125. Litterio MC, Prieto MAV, Adamo AM, Elesgaray R, Oteiza PI, Galleano M, et al. (-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability. J Nutr Biochem 2015; 26:745-751.
126. Liang YR, Ma SC, Luo XY, Xu JY, Wu MY, Luo YW, et al. Effects of green tea on blood pressure and hypertension-induced cardiovascular damage in spontaneously hypertensive rat. Food Sci Biotechnol 2011; 20:93-98.
127. Qian BJ, Tian CC, Ling XH, Yu LL, Ding FY, Huo JH, et al. miRNA-150-5p associate with antihypertensive effect of epigallocatechin-3-gallate revealed by aorta miRNome analysis of spontaneously hypertensive rat. Life Sci 2018; 203:193-202.
128. Szulinska M, Stepien M, Kregielska-Narozna M, Suliburska J, Skrypnik D, Bak-Sosnowska M, et al. Effects of green tea supplementation on inflammation markers, antioxidant status and blood pressure in NaCl-induced hypertensive rat model. Food Nutr Res 2017; 61:1295525.
129. Wang MH, Chang WJ, Soung HS, Chang KC. (-)-Epigallocatechin-3-gallate decreases the impairment in learning and memory in spontaneous hypertension rats. Behav Pharmacol 2012; 23:771-780.
130. Yi QY, Li HB, Qi J, Yu XJ, Huo CJ, Li X, et al. Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines. Toxicol Lett 2016; 262:105-113.
131. Yi QY, Qi J, Yu XJ, Li HB, Zhang Y, Su Q, et al. Paraventricular nucleus infusion of epigallocatechin-3-O-gallate improves renovascular hypertension. Cardiovasc Toxicol 2016; 16:276-285.
132. Nogueira LP, Nogueira Neto JF, Klein MR, Sanjuliani AF. Short-term effects of green tea on blood pressure, endothelial function, and metabolic profile in obese prehypertensive women: A crossover randomized clinical trial. J Am Coll Nutr 2017; 36:108-115.
133. Arazi H, Samami N, Kheirkhah J, Taati B. The effect of three weeks green tea extract consumption on blood pressure, heart rate responses to a single bout resistance exercise in hypertensive women. High Blood Press Cardiovasc Prev 2014; 21:213-219.
134. Ullah N, Rafique N, Nazir A, Anwar S, Altaf N, Ahmed G. Effect of decoction of Camellia sinensis on blood pressure and heart rate. Medical Forum Mon 2011; 22:46-48.
135. Son JT, Lee E. Effects of green tea ingestion on postprandial drops in blood pressure in older adults. J Gerontol Nurs 2012; 38:30-38.
136. Ahmad RS, Butt MS, Huma N, Sultan MT. Green tea catechins based functional drink (Green cool) improves the antioxidant status of SD rats fed on high cholesterol and sucrose diets. Pak J Pharm Sci 2013; 26:721-726.
137. de Moraes BB, Pasquini G, Aguiar O, Gollucke APB, Ihara SSM, Tenorio NM, et al. Protective effects of green tea against hepatic injury induced by high-cholesterol diet in rats: histopathological analysis, oxidative DNA damage and COX-2 expression. Hepatol Int 2011; 5:965-974.
138. Jung MH, Seong PN, Kim MH, Myong NH, Chang MJ. Effect of green tea extract microencapsulation on hypertriglyceridemia and cardiovascular tissues in high fructose-fed rats. Nutr Res Pract 2013; 7:366-372.
139. Labdi A, Amiali M, Bachir YN, Merouane A, Dahman-Zouambi A, Koceir EA, et al. Green tea extract attenuates non alcoholic fatty liver disease by decreasing hyperlipidemia and enhancing Superoxide dismutase activity in cholesterol-fed rats. Med J Nutrition Metab 2018; 11:295-306.
140. El-Sayed Mostafa U. Effect of green tea and green tea rich with catechin on blood glucose levels, serum lipid profile and liver and kidney functions in diabetic rats. Jordan J Biol Sci 2014; 7:7-12.
141. Li SY, Tse IMY, Li ETS. Maternal green tea extract supplementation to rats fed a high-fat diet ameliorates insulin resistance in adult male offspring. J Nutr Biochem 2012; 23:1655-1660.
142. Hong ZY, Xu YQ, Yin JF, Jin JC, Jiang YW, Du QZ. Improving the Effectiveness of (-)-Epigallocatechin Gallate (EGCG) against rabbit atherosclerosis by EGCG-Loaded nanoparticles prepared from chitosan and polyaspartic acid. J Agric Food Chem 2014; 62:12603-12609.
143. Ramachandran B, Jayavelu S, Murhekar K, Rajkumar T. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia. Toxicol Rep 2016; 3:336-345.
144. Bartikova H, Bousova I, Matouskova P, Szotakova B, Skalova L. Effect of green tea extract-enriched diets on insulin and leptin levels, oxidative stress parameters and antioxidant enzymes activities in obese mice. Polish J Food Nutr Sci 2017; 67:233-240.
145. Chen T, Liu AB, Sun S, Ajami NJ, Ross MC, Wang H, et al. Green tea polyphenols modify the gut microbiome in db/db mice as co-abundance groups correlating with the blood glucose lowering effect. Mol Nutr Food Res 2019; 63:e1801064.
146. Al-Shaeli SJ, Watkins AJ, Brown JE. Effect of green tea extract and epigallocatechin gallate on glucose and insulin levels in high glucose fed mice. Diabet Med 2017; 34:75-76.
147. Fu Z, Zhen W, Yuskavage J, Liu DM. Epigallocatechin gallate delays the onset of type 1 diabetes in spontaneous non-obese diabetic mice. Br J Nutr 2011; 105:1218-1225.
148. Bao S, Cao Y, Fan C, Fan Y, Bai S, Teng W, et al. Epigallocatechin gallate improves insulin signaling by decreasing toll-like receptor 4 (TLR4) activity in adipose tissues of high-fat diet rats. Mol Nutr Food Res 2014; 58:677-686.
149. Catanzaro DP, Mena Laura EE, Cestari TM, Arantes RVN, Garlet GP, Taga R, et al. Green tea prevents vascular disturbs and attenuates periodontal breakdown in long-term hyperglycaemia in T1D rats. J Clin Periodontol 2018; 45:557-569.
150. Chen TS, Liou SY, Kuo CH, Pan LF, Yeh YL, Liou J, et al. Green tea epigallocatechin gallate enhances cardiac function restoration through survival signaling expression in diabetes mellitus rats with autologous adipose tissue-derived stem cells. J Appl Physiol 2017; 123:1081-1091.
151. Dash RP, Ellendula B, Agarwal M, Nivsarkar M. Increased intestinal P-glycoprotein expression and activity with progression of diabetes and its modulation by epigallocatechin-3-gallate: Evidence from pharmacokinetic studies. Eur J Pharmacol 2015; 767:67-76.
152. Fiorino P, Evangelista FS, Santos F, Magri FMM, Delorenzi J, Ginoza M, et al. The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes. Exp Diabetes Res 2012; 2012:309231
153. Li Y, Zhao S, Zhang W, Zhao P, He B, Wu N, et al. Epigallocatechin-3-O-gallate (EGCG) attenuates FFAs-induced peripheral insulin resistance through AMPK pathway and insulin signaling pathway in vivo. Diabetes Res Clin Pract 2011; 93:205-214.
154. Lombo C, Morgado C, Tavares I, Neves D. Effects of prolonged ingestion of epigallocatechin gallate on diabetes type 1-induced vascular modifications in the erectile tissue of rats. Int J Impot Res 2016; 28:133-138.