Letter to the editor

Current update on the protective effect of epicatechin in neurodegenerative diseases

Riya Thapa1, Gaurav Gupta1,2,3, Piyush Dave1, Santosh Kumar Singh1, Abhay Raizaday1, Waleed Hassan Almalki4, Govind Vyas5, Sachin Kumar Singh6,7, Kamal Dua7,8, Yogendra Singh9[*]

1School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura 302017, Jaipur, India

2Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

3Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India

4Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

5Inva-Health Inc, Cranbury, NJ 08512, USA

6School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India

7Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia

8Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia

9Department of Pharmacology, Maharishi Arvind College of Pharmacy, Ambabari Circle, Ambabari, Jaipur, 302023, India

EXCLI J 2022;21:Doc897


Neurodegenerative diseases are characterized by the progressive loss of neural structures instead of the selective neuronal loss caused by metabolic or toxic disorders. Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis are among the several neurodegenerative diseases for which there is no treatment (Ruz et al., 2020[21]). New and better treatment strategies are urgently required to tackle these fatal illnesses. For example, epicatechin is one of the most prevalent and plentiful flavonoids (Figure 1(Fig. 1)). Numerous organs and tissues, including the heart, skeletal muscle, and neurons, have been studied, and epicatechin has been associated with mitochondrial improvement (Panneerselvam et al., 2013[19]). Epicatechin has been demonstrated to aid in treating neurodegenerative diseases, although there is little data to back this claim (Shaki et al., 2017[22]). The discoveries will also offer researchers a roadmap for developing neuroprotective drugs that are safe and effective (Table 1(Tab. 1); References in Table 1: Al-Amri et al., 2013[1]; Ali et al., 2021[2], 2022[3]; Avramovich-Tirosh et al., 2007[4]; Beasley et al., 2019[5]; Bitu Pinto et al., 2015[6]; Cano et al., 2021[7]; Cuevas et al., 2009[8]; Diaz et al., 2019[9]; Ehrnhoefer et al., 2006[10]; Ferruzzi et al., 2009[11]; Koh et al., 2006[12]; Kumar and Kumar, 2009[13]; Li et al., 2004[14]; Lim et al., 2013[15]; Mandel et al., 2004[16]; Nan et al., 2021[17]; N'Go et al., 2021[18]; Rubio-Osornio et al., 2015[20]; Shaki et al., 2017[22]; Siddique et al., 2014[23]; Tseng et al., 2020[24]; Wang et al., 2012[25]; Xu et al., 2006[26]; Ye et al., 2012[27]; Zhou et al., 2019[28]).

Conflict of interest

The authors declare no conflict of interest.



1. Al-Amri JS, Hagras MM, Mohamed IM. Effect of epigallocatechin-3-gallate on inflammatory mediators release in LPS-induced Parkinson's disease in rats. Indian J Exp Biol. 2013;51:357-62
2. Ali AA, Abd El-Fattah AI, Abu-Elfotuh K, Elariny HA. Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer's disease in rats. Int Immunopharmacol. 2021;96:107729. doi: 10.1016/j.intimp.2021.107729
3. Ali AA, Khalil MG, Abd El-Latif DM, Okda T, Abdelaziz AI, Abu-Elfotuh K, et al. The influence of vinpocetine alone or in combination with Epigallocatechin-3-gallate, Coenzyme COQ10, Vitamin E and Selenium as a potential neuroprotective combination against aluminium-induced Alzheimer's disease in Wistar Albino Rats. Arch Gerontol Geriatr. 2022;98:104557. doi: 10.1016/j.archger.2021.104557
4. Avramovich-Tirosh Y, Reznichenko L, Mit T, Zheng H, Fridkin M, Weinreb O, et al. Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M-30 and green tea polyphenol, EGCG. Curr Alzheimer Res. 2007;4:403-11. doi: 10.2174/156720507781788927
5. Beasley M, Stonebraker AR, Hasan I, Kapp KL, Liang BJ, Agarwal G, et al. Lipid membranes influence the ability of small molecules to inhibit huntingtin fibrillization. Biochemistry. 2019;58:4361-73. doi: 10.1021/acs.biochem.9b00739
6. Bitu Pinto N, da Silva Alexandre B, Neves KR, Silva AH, Leal LK, Viana GS. Neuroprotective properties of the standardized extract from Camellia sinensis (green tea) and its main bioactive components, epicatechin and epigallocatechin gallate, in the 6-OHDA model of Parkinson's disease. Evid Based Complement Alternat Med. 2015;2015:161092. doi: 10.1155/2015/161092
7. Cano A, Ettcheto M, Espina M, Auladell C, Folch J, Kühne BA, et al. Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice. Nanomedicine. 2021;16(1):19-35. doi: 10.2217/nnm-2020-0239
8. Cuevas E, Limón D, Pérez-Severiano F, Díaz A, Ortega L, Zenteno E, et al. Antioxidant effects of epicatechin on the hippocampal toxicity caused by amyloid-beta 25-35 in rats. Eur J Pharmacol. 2009;616:122-7. doi: 10.1016/j.ejphar.2009.06.013
9. Diaz A, Treviño S, Pulido-Fernandez G, Martínez-Muñoz E, Cervantes N, Espinosa B, et al. Epicatechin reduces spatial memory deficit caused by amyloid-β25⁻35 toxicity modifying the heat shock proteins in the CA1 region in the hippocampus of rats. Antioxidants (Basel). 2019;8(5):113. doi: 10.3390/antiox8050113
10. Ehrnhoefer D, Duennwald M, Markovic P, Wacker J, Engemann S, Roark M, et al. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet. 2006;15:2743-51. doi: 10.1093/hmg/ddl210
11. Ferruzzi MG, Lobo JK, Janle EM, Cooper B, Simon JE, Wu Q-L, et al. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease. J Alzheimer's Dis. 2009;18:113-24. doi: 10.3233/JAD-2009-1135
12. Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, et al. The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett. 2006;395:103-7. doi: 10.1016/j.neulet.2005.10.056
13. Kumar P, Kumar A. Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Food Chem Toxicol. 2009;47:2522-30. doi: 10.1016/j.fct.2009.07.011
14. Li R, Huang YG, Fang D, Le WD. (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res. 2004;78:723-31. doi: 10.1002/jnr.20315
15. Lim HJ, Shim SB, Jee SW, Lee SH, Lim CJ, Hong JT, et al. Green tea catechin leads to global improvement among Alzheimer's disease-related phenotypes in NSE/hAPP-C105 Tg mice. J Nutr Biochem. 2013;24:1302-13. doi: 10.1016/j.jnutbio.2012.10.005
16. Mandel S, Maor G, Youdim MB. Iron and alpha-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol (-)-epigallocatechin-3-gallate. J Mol Neurosci. 2004;24:401-16. doi: 10.1385/jmn:24:3:401
17. Nan S, Wang P, Zhang Y, Fan J. Epigallocatechin-3-gallate provides protection against Alzheimer's disease-induced learning and memory impairments in rats. Drug Des Devel Ther. 2021;15:2013-24. doi: 10.2147/dddt.s289473
18. N'Go PK, Ahami OTA, El Hessni A, Azzaoui FZ, Aboussaleh Y, Tako AN. Neuroprotective effects of the Chrysophyllum perpulchrum extract against an Alzheimer-like rat model of β amyloid(1-40) intrahippocampal injection. Transl Neurosci. 2021;12:545-60. doi: 10.1515/tnsci-2020-0183
19. Panneerselvam M, Ali SS, Finley JC, Kellerhals SE, Migita MY, Head BP, et al. Epicatechin regulation of mitochondrial structure and function is opioid receptor dependent. Mol Nutr Food Res. 2013;57:1007-14. doi: 10.1002/mnfr.201300026
20. Rubio-Osornio M, Gorostieta-Salas E, Montes S, Pérez-Severiano F, Rubio C, Gómez C, et al. Epicatechin reduces striatal MPP⁺-induced damage in rats through slight increases in SOD-Cu,Zn activity. Oxid Med Cell Longev. 2015;2015:276039. doi: 10.1155/2015/276039
21. Ruz C, Alcantud JL, Vives Montero F, Duran R, Bandres-Ciga S. Proteotoxicity and neurodegenerative diseases. Int J Mol Sci. 2020;21(16):5646. doi: 10.3390/ijms21165646
22. Shaki F, Shayeste Y, Karami M, Akbari E, Rezaei M, Ataee R. The effect of epicatechin on oxidative stress and mitochondrial damage induced by homocycteine using isolated rat hippocampus mitochondria. Res Pharm Sci. 2017;12:119-27. doi: 10.4103/1735-5362.202450
23. Siddique YH, Jyoti S, Naz F. Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of Parkinson's disease. J Diet Suppl. 2014;11:121-30. doi: 10.3109/19390211.2013.859207
24. Tseng HC, Wang MH, Chang KC, Soung HS, Fang CH, Lin YW, et al. Protective effect of (-)epigallocatechin-3-gallate on rotenone-induced Parkinsonism-like symptoms in rats. Neurotox Res. 2020;37:669-82. doi: 10.1007/s12640-019-00143-6
25. Wang J, Ferruzzi MG, Ho L, Blount J, Janle EM, Gong B, et al. Brain-targeted proanthocyanidin metabolites for Alzheimer's disease treatment. J Neurosci. 2012;32:5144-50. doi: 10.1523/jneurosci.6437-11.2012
26. Xu Z, Chen S, Li X, Luo G, Li L, Le W. Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res. 2006;31:1263-9. doi: 10.1007/s11064-006-9166-z
27. Ye Q, Ye L, Xu X, Huang B, Zhang X, Zhu Y, et al. Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1α signaling pathway. BMC Complement Altern Med. 2012;12:82. doi: 10.1186/1472-6882-12-82
28. Zhou W, Chen L, Hu X, Cao S, Yang J. Effects and mechanism of epigallocatechin-3-gallate on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in Parkinson rats. Neuroreport. 2019;30:60-5. doi: 10.1097/wnr.0000000000001149

Figure 1: Chemical structure of epicatechin


Table 1: An update on the protective effect of epicatechin in various neurodegenerative diseases

[*] Corresponding Author:

Yogendra Singh, Department of Pharmacology, Maharishi Arvind College of Pharmacy, Ambabari Circle, Ambabari, Jaipur, 302023, India, eMail: yogi.singh1219@gmail.com or yogendra.singh119@gmail.com