An Overview of the Therapeutic Efficacy of (-)-Epicatechin in the Management of Diabetes Mellitus

Article ID: e310823220576 Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background and Aims: Diabetes mellitus is a chronic metabolic disorder affecting global public health. Since ancient, natural-based compounds are widely used for multiple indications of diabetes.

Methods: The natural-based (-)-Epicatechin has enormous biological functions including antioxidant and anti-inflammatory activities. This review mainly focuses on the importance of epicatechin in the control of pathogenesis involved in diabetic mellitus. Additionally, its possible mechanisms involved in beta cell regeneration, insulin secretion, and insulin sensitivity.

Results: The present article explored the potential antioxidant, mitochondrial protection, and antiinflammatory properties using the preclinical and clinical model, and also established the role of (-)- Epicatechin in the mitigation of diabetic-associated complications. Lastly, the article mentioned the limitation of the use of epicatechin.

Conclusion: This will provide new insight to budding scientists for the development of novel bioactivebased pharmaceuticals for the management of diabetic mellitus.

Graphical Abstract

[1]
Mariadoss, A.V.A.; Sivakumar, A.S.; Lee, C.H.; Kim, S.J. Diabetes mellitus and diabetic foot ulcer: Etiology, biochemical and molecular based treatment strategies via gene and nanotherapy. Biomed. Pharmacother., 2022, 151, 113134.
[http://dx.doi.org/10.1016/j.biopha.2022.113134] [PMID: 35617802]
[2]
Wickramasinghe, A.S.D.; Kalansuriya, P.; Attanayake, A.P. Nanoformulation of plant-based natural products for type 2 diabetes mellitus: From formulation design to therapeutic applications. Curr. Ther. Res. Clin. Exp., 2022, 96, 100672.
[http://dx.doi.org/10.1016/j.curtheres.2022.100672] [PMID: 35586563]
[3]
Prakash, M.; Basavaraj, B.V.; Chidambara Murthy, K.N. Biological functions of epicatechin: Plant cell to human cell health. J. Funct. Foods, 2019, 52, 14-24.
[http://dx.doi.org/10.1016/j.jff.2018.10.021]
[4]
Bettaieb, A.; Vazquez Prieto, M.A.; Rodriguez Lanzi, C.; Miatello, R.M.; Haj, F.G.; Fraga, C.G.; Oteiza, P.I. (−)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic. Biol. Med., 2014, 72, 247-256.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.04.011] [PMID: 24746618]
[5]
Chun, J. H.; Henckel, M. M.; Knaub, L. A.; Hull, S. E.; Pott, G. B.; Ramirez, D. G.; Keller, A. C. (−)-Epicatechin reverses glucose intolerance in rats housed at thermoneutrality. Planta Med., 2022, 88(09/10), 735-744.
[6]
Borah, N.; Chetia, P.; Tamuly, C. Arengawesterhoutii Griff.: Bioactive constituents, nutraceuticals, antioxidant and anti-diabetic potential of stem extract and an insight into molecular docking analysis. Nat. Prod. Res., 2023, 37(13), 2293-2297.
[PMID: 35133235]
[7]
García-Díez, E.; López-Oliva, M.E.; Pérez-Jiménez, J.; Martín, M.A.; Ramos, S. Metabolic regulation of (−)-epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid on the glucose uptake, lipid accumulation and insulin signalling in cardiac H9c2 cells. Food Funct., 2022, 13(10), 5602-5615.
[http://dx.doi.org/10.1039/D2FO00182A] [PMID: 35502961]
[8]
Liu, Z.H.; Li, B. (-)-Epicatechin and β-glucan from highland barley grain modulated glucose metabolism and showed synergistic effect via Akt pathway. J. Funct. Foods, 2021, 87, 104793.
[http://dx.doi.org/10.1016/j.jff.2021.104793]
[9]
Zhang, K.; Chen, X.L.; Zhao, X.; Ni, J.Y.; Wang, H.L.; Han, M.; Zhang, Y.M. Antidiabetic potential of Catechu via assays for α-glucosidase, α-amylase, and glucose uptake in adipocytes. J. Ethnopharmacol., 2022, 291, 115118.
[http://dx.doi.org/10.1016/j.jep.2022.115118] [PMID: 35202712]
[10]
Rizvi, S.I.; Zaid, M.A. Insulin-like effect of (-)epicatechin on erythrocyte membrane acetylcholinesterase activity in type 2 diabetes mellitus. Clin. Exp. Pharmacol. Physiol., 2001, 28(9), 776-778.
[http://dx.doi.org/10.1046/j.1440-1681.2001.03513.x] [PMID: 11553037]
[11]
Lim, E.Y.; Lee, C.; Kim, Y.T. The antinociceptive potential of camellia japonica leaf extract, (−)-epicatechin, and rutin against chronic constriction injury-induced neuropathic pain in rats. Antioxidants, 2022, 11(2), 410.
[http://dx.doi.org/10.3390/antiox11020410] [PMID: 35204294]
[12]
Quine, S.D.; Raghu, P.S. Effects of (-)-epicatechin, a flavonoid on lipid peroxidation and antioxidants in streptozotocin-induced diabetic liver, kidney and heart. Pharmacol. Rep., 2005, 57(5), 610-615.
[PMID: 16227644]
[13]
Fu, Z.; Yuskavage, J.; Liu, D. Dietary flavonol epicatechin prevents the onset of type 1 diabetes in nonobese diabetic mice. J. Agric. Food Chem., 2013, 61(18), 4303-4309.
[http://dx.doi.org/10.1021/jf304915h] [PMID: 23578364]
[14]
Chakravarthy, B.K.; Gupta, S.; Gambhir, S.S.; Gode, K.D. The prophylactic action of (−)-Epicatechin against alloxan induced diabetes in rats. Life Sci., 1981, 29(20), 2043-2047.
[http://dx.doi.org/10.1016/0024-3205(81)90660-3] [PMID: 7031399]
[15]
Rizvi, S.I.; Zaid, M.A.; Anis, R.; Mishra, N. Protective role of tea catechins against oxidation-induced damage of type 2 diabetic erythrocytes. Clin. Exp. Pharmacol. Physiol., 2005, 32(1-2), 70-75.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04160.x] [PMID: 15730438]
[16]
Si, H.; Fu, Z.; Babu, P.V.A.; Zhen, W.; LeRoith, T.; Meaney, M.P.; Voelker, K.A.; Jia, Z.; Grange, R.W.; Liu, D. Dietary epicatechin promotes survival of obese diabetic mice and Drosophila melanogaster. J. Nutr., 2011, 141(6), 1095-1100.
[http://dx.doi.org/10.3945/jn.110.134270] [PMID: 21525262]
[17]
Cordero-Herrera, I.; Chen, X.; Ramos, S.; Devaraj, S. (−)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes. Eur. J. Nutr., 2017, 56(3), 1369-1373.
[http://dx.doi.org/10.1007/s00394-015-1136-2] [PMID: 26704714]
[18]
Kim, M.J.; Ryu, G.R.; Kang, J.H.; Sim, S.S.; Min, D.S.; Rhie, D.J.; Yoon, S.H.; Hahn, S.J.; Jeong, I.K.; Hong, K.J.; Kim, M.S.; Jo, Y.H. Inhibitory effects of epicatechin on interleukin-1β-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-κB activation. Biochem. Pharmacol., 2004, 68(9), 1775-1785.
[http://dx.doi.org/10.1016/j.bcp.2004.06.031] [PMID: 15450943]
[19]
Martín, M.Á.; Fernández-Millán, E.; Ramos, S.; Bravo, L.; Goya, L. Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress. Mol. Nutr. Food Res., 2014, 58(3), 447-456.
[http://dx.doi.org/10.1002/mnfr.201300291] [PMID: 24115486]
[20]
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]
[21]
El-Remessy, A.B.; Ali, T.K.; Pillai, B.A.; Matragoon, S. Epicatechin prevents gliosis and neuronal death in diabetes: Critical role of MMP-7. Invest. Ophthalmol. Vis. Sci., 2009, 50(13), 5375-5375.
[22]
Álvarez Cilleros, D.; López-Oliva, M.E.; Martín, M.Á.; Ramos, S. (−)-Epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid protect against high glucose and lipopolysaccharide-induced inflammation in renal proximal tubular cells through NOX-4/p38 signalling. Food Funct., 2020, 11(10), 8811-8824.
[http://dx.doi.org/10.1039/D0FO01805H] [PMID: 32959859]
[23]
Shimizu, M.; Kobayashi, Y.; Suzuki, M.; Satsu, H.; Miyamoto, Y. Regulation of intestinal glucose transport by tea catechins. Biofactors, 2000, 13(1-4), 61-65.
[http://dx.doi.org/10.1002/biof.5520130111] [PMID: 11237201]
[24]
Yasui, K.; Paeng, N.; Miyoshi, N.; Suzuki, T.; Taguchi, K.; Ishigami, Y.; Fukutomi, R.; Imai, S.; Isemura, M.; Nakayama, T. Effects of a catechin-free fraction derived from green tea on gene expression of enzymes related to lipid metabolism in the mouse liver. Biomed. Res., 2012, 33(1), 9-13.
[http://dx.doi.org/10.2220/biomedres.33.9] [PMID: 22361881]
[25]
Ahmad, F.; Khalid, P.; Khan, M.M.; Rastogi, A.K.; Kidwai, J.R. Insulin like activity in (−) Epicatechin. Acta diabetologia latina, 1989, 4, 291-300.
[26]
Biswas, M.; Bhattacharya, S.; Karan, T.K.; Kar, B.; Kumar, R.B.; Ghosh, A.K.; Haldar, P.K. Antidiabetic activity and antioxidant activity of Dregeavolubilis fruit in streptozotocin-induced diabetic rats. Asian J. Chem., 2011, 23(10), 4503-4507.
[27]
Rizvi, S.I.; Zaid, M.A. Intracellular reduced glutathione content in normal and type 2 diabetic erythrocytes: Effect of insulin and (-)epicatechin. J. Physiol. Pharmacol., 2001, 52(3), 483-488.
[PMID: 11596865]
[28]
Kar, B.; Rout, R.C.; Panda, P.K.; Behera, L.; Panda, S.K.; Pattnaik, G.; Bhattacharya, S. Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models. J. Adv. Pharm. Technol. Res., 2022, 13(2), 106-110.
[http://dx.doi.org/10.4103/japtr.japtr_300_21] [PMID: 35464654]
[29]
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm. J., 2016, 24(5), 547-553.
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[30]
Li, Y.M.; Chan, H.Y.E.; Huang, Y.; Chen, Z.Y. Green tea catechins upregulate superoxide dismutase and catalase in fruit flies. Mol. Nutr. Food Res., 2007, 51(5), 546-554.
[http://dx.doi.org/10.1002/mnfr.200600238] [PMID: 17440995]
[31]
Moreno-Ulloa, A.; Nogueira, L.; Rodriguez, A.; Barboza, J.; Hogan, M.C.; Ceballos, G.; Villarreal, F.; Ramirez-Sanchez, I. Recovery of indicators of mitochondrial biogenesis, oxidative stress, and aging with (-)-epicatechin in senile mice. J. Gerontol. A Biol. Sci. Med. Sci., 2015, 70(11), 1370-1378.
[http://dx.doi.org/10.1093/gerona/glu131] [PMID: 25143004]
[32]
Vinson, J.A.; Proch, J.; Bose, P.; Muchler, S.; Taffera, P.; Shuta, D.; Samman, N.; Agbor, G.A. Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American Diets. J. Agric. Food Chem., 2006, 54(21), 8071-8076.
[http://dx.doi.org/10.1021/jf062175j] [PMID: 17032011]
[33]
Khamaisi, M.; Potashnik, R.; Tirosh, A.; Demshchak, E.; Rudich, A.; Trischler, H.; Wessel, K.; Bashan, N. Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats. Metabolism, 1997, 46(7), 763-768.
[http://dx.doi.org/10.1016/S0026-0495(97)90120-7] [PMID: 9225829]
[34]
Cremonini, E.; Fraga, C.G.; Oteiza, P.I. (–)-Epicatechin in the control of glucose homeostasis: Involvement of redox-regulated mechanisms. Free Radic. Biol. Med., 2019, 130, 478-488.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.010] [PMID: 30447350]
[35]
Petersen, K.F.; Shulman, G.I. Etiology of insulin resistance. Am. J. Med., 2006, 119(5)(Suppl. 1), S10-S16.
[http://dx.doi.org/10.1016/j.amjmed.2006.01.009] [PMID: 16563942]
[36]
Ueda-Wakagi, M.; Mukai, R.; Fuse, N.; Mizushina, Y.; Ashida, H. 3-O-acyl-epicatechins increase glucose uptake activity and GLUT4 translocation through activation of PI3K signaling in skeletal muscle cells. Int. J. Mol. Sci., 2015, 16(7), 16288-16299.
[http://dx.doi.org/10.3390/ijms160716288] [PMID: 26193264]
[37]
Yamashita, Y.; Wang, L.; Nanba, F.; Ito, C.; Toda, T.; Ashida, H. Procyanidin promotes translocation of glucose transporter 4 in muscle of mice through activation of insulin and AMPK signaling pathways. PLoS One, 2016, 11(9), e0161704.
[http://dx.doi.org/10.1371/journal.pone.0161704] [PMID: 27598258]
[38]
Furuyashiki, T.; Nagayasu, H.; Aoki, Y.; Bessho, H.; Hashimoto, T.; Kanazawa, K.; Ashida, H. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells. Biosci. Biotechnol. Biochem., 2004, 68(11), 2353-2359.
[http://dx.doi.org/10.1271/bbb.68.2353] [PMID: 15564676]
[39]
Garcia, C.; Feve, B.; Ferré, P.; Halimi, S.; Baizri, H.; Bordier, L.; Guiu, G.; Dupuy, O.; Bauduceau, B.; Mayaudon, H. Diabetes and inflammation: Fundamental aspects and clinical implications. Diabetes Metab., 2010, 36(5), 327-338.
[http://dx.doi.org/10.1016/j.diabet.2010.07.001] [PMID: 20851652]
[40]
Barnett, C.F.; Moreno-Ulloa, A.; Shiva, S.; Ramirez-Sanchez, I.; Taub, P.R.; Su, Y.; Ceballos, G.; Dugar, S.; Schreiner, G.; Villarreal, F. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (−)-epicatechin in healthy volunteers. Food Funct., 2015, 6(3), 824-833.
[http://dx.doi.org/10.1039/C4FO00596A] [PMID: 25598082]
[41]
Tanabe, K.; Tamura, Y.; Lanaspa, M.A.; Miyazaki, M.; Suzuki, N.; Sato, W.; Maeshima, Y.; Schreiner, G.F.; Villarreal, F.J.; Johnson, R.J.; Nakagawa, T. Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy. Am. J. Physiol. Renal Physiol., 2012, 303(9), F1264-F1274.
[http://dx.doi.org/10.1152/ajprenal.00227.2012] [PMID: 22933302]
[42]
Gu, Y.; Yu, S.; Lambert, J.D. Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice. Eur. J. Nutr., 2014, 53(1), 149-158.
[http://dx.doi.org/10.1007/s00394-013-0510-1] [PMID: 23494741]
[43]
Papatheodorou, K.; Banach, M.; Bekiari, E.; Rizzo, M.; Edmonds, M. Complications of diabetes 2017. J. Diabetes Res., 2018, 2018, 1-4.
[http://dx.doi.org/10.1155/2018/3086167] [PMID: 29713648]
[44]
Chennasamudram, S.P.; Kudugunti, S.; Boreddy, P.R.; Moridani, M.Y.; Vasylyeva, T.L. Renoprotective effects of (+)-catechin in streptozotocin-induced diabetic rat model. Nutr. Res., 2012, 32(5), 347-356.
[http://dx.doi.org/10.1016/j.nutres.2012.03.015] [PMID: 22652374]
[45]
Villarreal, F.; Moreno‐Ulloa, A.; Ciaraldi, T.; Best, B.; Ramirez‐Sanchez, I.; Ceballos, G.; Henry, R. Clinical pharmacokinetics and preclinical pharmacodynamics of (+)‐epicatechin on cardiometabolic endpoints. FASEB J., 2017, 31, 676-1.
[46]
Qureshi, M.Y.; Patterson, M.C.; Clark, V.; Johnson, J.N.; Moutvic, M.A.; Driscoll, S.W.; Kemppainen, J.L.; Huston, J., III; Anderson, J.R.; Badley, A.D.; Tebben, P.J.; Wackel, P.; Oglesbee, D.; Glockner, J.; Schreiner, G.; Dugar, S.; Touchette, J.C.; Gavrilova, R.H. Safety and efficacy of (+)‐epicatechin in subjects with Friedreich’s ataxia: A phase II, open‐label, prospective study. J. Inherit. Metab. Dis., 2021, 44(2), 502-514.
[http://dx.doi.org/10.1002/jimd.12285] [PMID: 32677106]