Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Epigallocatechin Gallate Protects Diabetes Mellitus Rats Complicated with Cardiomyopathy through TGF-β1/JNK Signaling Pathway

Author(s): Liuming Gui, Fengxian Wang, Xiangka Hu, Xiaojuan Liu, He Yang, Zengxiaorui Cai, Mushuang Qi and Chunmei Dai*

Volume 28, Issue 33, 2022

Published on: 23 September, 2022

Page: [2758 - 2770] Pages: 13

DOI: 10.2174/1381612828666220902115437

Price: $65

Abstract

Background: Epigallocatechin gallate (EGCG) is the main component of rhubarb tannin, with antioxidant, anti-angiogenic, anti-cancer and antiviral activities. Diabetes mellitus (DM) is a high blood sugar and protein metabolism disorder syndrome, which is caused by absolute or relative factors, such as deficiency of insulin and oxidative stress. Diabetes cardiomyopathy (DCM) is one of the most frequent complications of DM.

Objective: This study aims to explore whether EGCG can improve diabetic complication, myocardial fibrosis, in diabetic rats with an intraperitoneal injection of streptozotocin (STZ) through the transforming growth factor β1 (TGF-β1)/C-Jun N -terminal kinase (JNK) signaling pathway.

Methods: 50 male SD rats were randomly divided into five groups, including the control group, model group, and EGCG drug groups (10 mg/kg, 20 mg/kg, 40 mg/kg), with 10 rats in each group. Rats, except for the control group, were intraperitoneally injected with STZ (65 mg/kg) to induce the diabetic rats model. EGCG drug groups were given distilled water according to the dose, while the control group and model group were given the same volume of distilled water for 12 weeks. The levels of glucose (GLU), triglyceride (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by ELISA of all rats. Myocardial function was observed by HE, Masson staining and Sirius red staining in DCM rats. Immunohistochemistry was used to detect the expression of Collagen I (COL-I) and Collagen III (COL-III), and detect the degree of myocardial fibrosis of DM rats. Western blot was used to detect the expression of matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinase (TIMPs), TGF-β1, JNK and p-JNK in the myocardium.

Results: Compared to the model group, the levels of GLU, TG, CHO, and LDL in serum were decreased while the level of HDL in serum was increased in EGCG groups rats; cardiac index and left ventricular mass index were decreased while heart function was improved in EGCG groups rats; the expressions of the COL-I and COL-III were decreased in EGCG groups, and the high dose group was the best; the expressions of TGF-β1, JNK, p-JNK, and TIMP-1 were down-regulated, and the expression of MMP-9 was up-regulated in EGCG groups.

Conclusion: The results demonstrated that EGCG could improve STZ-induced diabetic complication, i.e., myocardial fibrosis, in diabetic rats, and protect their heart through TGF-β1/JNK signaling pathway.

Keywords: EGCG, diabetic cardiomyopathy, fibrosis, TGF-β1/JNK, signalling pathway, myocardium.

« Previous
[1]
Dixon JB, Zimmet P, Alberti KG, Mbanya JC, Rubino F. Bariatric surgery for diabetes: The International Diabetes Federation takes a position. J Diabetes 2011; 3(4): 261-4.
[http://dx.doi.org/10.1111/j.1753-0407.2011.00144.x] [PMID: 21707957]
[2]
Mun KC, Mun KC. Effect of epigallocatechin gallate on renal function in cyclosporine-induced nephrotoxicity. Transplant Proc 2004; 36(7): 2133-4.
[http://dx.doi.org/10.1016/j.transproceed.2004.08.020] [PMID: 15518774]
[3]
Candido R, Forbes JM, Thomas MC, et al. A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res 2003; 92(7): 785-92.
[http://dx.doi.org/10.1161/01.RES.0000065620.39919.20] [PMID: 12623881]
[4]
Morrisey K, Evans RA, Wakefield L, Phillips AO. Translational regulation of renal proximal tubular epithelial cell transforming growth factor-beta1 generation by insulin. Am J Pathol 2001; 159(5): 1905-15.
[http://dx.doi.org/10.1016/S0002-9440(10)63037-4] [PMID: 11696451]
[5]
Tomlinson KC, Gardiner SM, Hebden RA, Bennett T. Functional consequences of streptozotocin-induced diabetes mellitus, with particular reference to the cardiovascular system. Pharmacol Rev 1992; 44(1): 103-50.
[PMID: 1557425]
[6]
Zhang L, Ding W, Wang Z, et al. Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy. J Transl Med 2016; 14(1): 109.
[http://dx.doi.org/10.1186/s12967-016-0849-1] [PMID: 27121077]
[7]
Zhou J, Zhou S, Tang J, et al. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 2009; 606(1-3): 262-8.
[http://dx.doi.org/10.1016/j.ejphar.2008.12.056] [PMID: 19374872]
[8]
Mizushige K, Yao L, Noma T, et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation 2000; 101(8): 899-907.
[http://dx.doi.org/10.1161/01.CIR.101.8.899] [PMID: 10694530]
[9]
Guan S, Ma Z, Wu Y, et al. Long-term administration of fasudil improves cardiomyopathy in streptozotocin-induced diabetic rats. Food Chem Toxicol 2012; 50(6): 1874-82.
[http://dx.doi.org/10.1016/j.fct.2012.03.006] [PMID: 22429817]
[10]
Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: Importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care 2001; 24(1): 5-10.
[http://dx.doi.org/10.2337/diacare.24.1.5] [PMID: 11194240]
[11]
Fischer M, Baessler A, Hense HW, et al. Prevalence of left ventricular diastolic dysfunction in the community results from a Doppler echocardiographic-based survey of a population sample. Eur Heart J 2003; 24(4): 320-8.
[http://dx.doi.org/10.1016/S0195-668X(02)00428-1] [PMID: 12581679]
[12]
Westermann D, Rutschow S, Jäger S, et al. Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: The role of angiotensin type 1 receptor antagonism. Diabetes 2007; 56(3): 641-6.
[http://dx.doi.org/10.2337/db06-1163] [PMID: 17327431]
[13]
Fowlkes V, Clark J, Fix C, et al. Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts. Life Sci 2013; 92(11): 669-76.
[http://dx.doi.org/10.1016/j.lfs.2013.01.003] [PMID: 23333820]
[14]
Jin Y, Shi Y, Zou Y, et al. Fenugreek prevents the development of STZ-Induced diabetic nephropathy in a rat model of diabetes. Evid Based Complement Alternat Med 2014; 2014: 259368.
[http://dx.doi.org/10.1155/2014/259368]
[15]
Yan J, Feng Z, Liu J, et al. Enhanced autophagy plays a cardinal role in mitochondrial dysfunction in type 2 diabetic Goto–Kakizaki (GK) rats: ameliorating effects of (-)-epigallocatechin-3-gallate. J Nutr Biochem 2012; 23(7): 716-24.
[http://dx.doi.org/10.1016/j.jnutbio.2011.03.014] [PMID: 21820301]
[16]
Suzuki H, Uchida K, Nitta K, Nihei H. Role of mitogen-activated protein kinase in the regulation of transforming growth factor-induced fibronectin accumulation in cultured renal interstitial fibroblasts. Clin Exp Nephrol 2004; 8(3): 188-95.
[http://dx.doi.org/10.1007/s10157-004-0297-8] [PMID: 15480895]
[17]
Hsieh SR, Hsu CS, Lu CH, Chen WC, Chiu CH, Liou YM. Epigallocatechin-3-gallate-mediated cardioprotection by Akt/GSK-3β/caveolin signalling in H9c2 rat cardiomyoblasts. J Biomed Sci 2013; 20(1): 86.
[http://dx.doi.org/10.1186/1423-0127-20-86] [PMID: 24251870]
[18]
Iso H, Date C, Wakai K, Fukui M, Tamakoshi A. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006; 144(8): 554-62.
[http://dx.doi.org/10.7326/0003-4819-144-8-200604180-00005] [PMID: 16618952]
[19]
Chen H, Zhang M, Xie B. Components and antioxidant activity of polysaccharide conjugate from green tea. Food Chem 2005; 90(1-2): 17-21.
[http://dx.doi.org/10.1016/j.foodchem.2004.03.001]
[20]
Sabu MC, Smitha K, Kuttan R. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol 2002; 83(1-2): 109-16.
[http://dx.doi.org/10.1016/S0378-8741(02)00217-9] [PMID: 12413715]
[21]
Babu PVA, Sabitha KE, Shyamaladevi CS. Green tea impedes dyslipidemia, lipid peroxidation, protein glycation and ameliorates Ca2+-ATPase and Na+/K+-ATPase activity in the heart of streptozotocin-diabetic rats. Chem Biol Interact 2006; 162(2): 157-64.
[http://dx.doi.org/10.1016/j.cbi.2006.05.020] [PMID: 16846594]
[22]
Wolfram S, Wang Y, Thielecke F. Anti-obesity effects of green tea: From bedside to bench. Mol Nutr Food Res 2006; 50(2): 176-87.
[http://dx.doi.org/10.1002/mnfr.200500102] [PMID: 16470636]
[23]
Song EK, Hur H, Han MK. Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice. Arch Pharm Res 2003; 26(7): 559-63.
[http://dx.doi.org/10.1007/BF02976881] [PMID: 12934649]
[24]
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(3): e91163.
[http://dx.doi.org/10.1371/journal.pone.0091163] [PMID: 24614112]
[25]
Yousaf S, Butt MS, Suleria HAR, 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(3): 545-56.
[http://dx.doi.org/10.1039/c3fo60203f] [PMID: 24473227]
[26]
Adikesavan G, Vinayagam MM, Abdulrahman LA, Chinnasamy T. (−)-Epigallocatechin-gallate (EGCG) stabilize the mitochondrial enzymes and inhibits the apoptosis in cigarette smoke-induced myocardial dysfunction in rats. Mol Biol Rep 2013; 40(12): 6533-45.
[http://dx.doi.org/10.1007/s11033-013-2673-5] [PMID: 24197690]
[27]
Xu X, Pan J, Zhou X. Amelioration of lipid profile and level of antioxidant activities by epigallocatechin-gallate in a rat model of atherogenesis. Heart Lung Circ 2014; 23(12): 1194-201.
[http://dx.doi.org/10.1016/j.hlc.2014.05.013] [PMID: 25027849]
[28]
Kim SJ, Li M, Jeong CW, et al. Epigallocatechin-3-gallate, a green tea catechin, protects the heart against regional ischemia–reperfusion injuries through activation of RISK survival pathways in rats. Arch Pharm Res 2014; 37(8): 1079-85.
[http://dx.doi.org/10.1007/s12272-013-0309-x] [PMID: 24307060]
[29]
Wolfram S, Raederstorff D, Preller M, et al. Epigallocatechin gallate supplementation alleviates diabetes in rodents. J Nutr 2006; 136(10): 2512-8.
[http://dx.doi.org/10.1093/jn/136.10.2512] [PMID: 16988119]
[30]
Osada K, Takahashi M, Hoshina S, Nakamura M, Nakamura S, Sugano M. Tea catechins inhibit cholesterol oxidation accompanying oxidation of low density lipoprotein in vitro. Comp Biochem Physiol C Toxicol Pharmacol 2001; 128(2): 153-64.
[http://dx.doi.org/10.1016/S1532-0456(00)00192-7] [PMID: 11239828]
[31]
Gokulakrisnan A, Jayachandran Dare B, Thirunavukkarasu C. Attenuation of the cardiac inflammatory changes and lipid anomalies by (−)-epigallocatechin-gallate in cigarette smoke-exposed rats. Mol Cell Biochem 2011; 354(1-2): 1-10.
[http://dx.doi.org/10.1007/s11010-011-0785-6] [PMID: 21633901]
[32]
Cha KH, Song DG, Kim SM, Pan CH. Inhibition of gastrointestinal lipolysis by green tea, coffee, and gomchui (Ligularia fischeri) tea polyphenols during simulated digestion. J Agric Food Chem 2012; 60(29): 7152-7.
[http://dx.doi.org/10.1021/jf301047f] [PMID: 22730927]
[33]
Saffari Y, Sadrzadeh SMH. Green tea metabolite EGCG protects membranes against oxidative damage in vitro. Life Sci 2004; 74(12): 1513-8.
[http://dx.doi.org/10.1016/j.lfs.2003.08.019] [PMID: 14729400]
[34]
Gan L, Meng Z, Xiong R, et al. Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice. Acta Pharmacol Sin 2015; 36(5): 597-605.
[http://dx.doi.org/10.1038/aps.2015.11] [PMID: 25891086]
[35]
Yamabe N, Yokozawa T, Oya T, Kim M. Therapeutic potential of (-)-epigallocatechin 3-O-gallate on renal damage in diabetic nephropathy model rats. J Pharmacol Exp Ther 2006; 319(1): 228-36.
[http://dx.doi.org/10.1124/jpet.106.107029] [PMID: 16835369]
[36]
Devika PT, Stanely Mainzen Prince P. Preventive effect of (-)epigallocatechin gallate on lipids, lipoproteins, and enzymes of lipid metabolism in isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol 2009; 23(6): 387-93.
[http://dx.doi.org/10.1002/jbt.20302] [PMID: 20024955]
[37]
Wei H, Meng Z. Epigallocatechin-3-gallate protects Na+ channels in rat ventricular myocytes against sulfite. Cardiovasc Toxicol 2010; 10(3): 166-73.
[http://dx.doi.org/10.1007/s12012-010-9075-x] [PMID: 20473584]
[38]
Chen G, Wang H, Zhang X, Yang ST. Nutraceuticals and functional foods in the management of hyperlipidemia. Crit Rev Food Sci Nutr 2014; 54(9): 1180-201.
[http://dx.doi.org/10.1080/10408398.2011.629354] [PMID: 24499150]
[39]
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(5): 366-72.
[http://dx.doi.org/10.4162/nrp.2013.7.5.366] [PMID: 24133615]
[40]
Bhatia S, Shukla R, Venkata Madhu S, Kaur Gambhir J, Madhava Prabhu K. Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy. Clin Biochem 2003; 36(7): 557-62.
[http://dx.doi.org/10.1016/S0009-9120(03)00094-8] [PMID: 14563450]
[41]
Schannwell CM, Schneppenheim M, Perings S, Plehn G, Strauer BE. Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy. Cardiology 2002; 98(1-2): 33-9.
[http://dx.doi.org/10.1159/000064682] [PMID: 12373045]
[42]
Hibi M, Lin A, Smeal T, Minden A, Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 1993; 7(11): 2135-48.
[http://dx.doi.org/10.1101/gad.7.11.2135] [PMID: 8224842]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy