Download PDF
Planta Med 2023; 89(13): 1229-1235
DOI: 10.1055/a-2111-7319
Natural Product Chemistry and Analytical Studies
Reviews

An Update on Impacts of Epigallocatechin Gallate Co-administration in Modulating Pharmacokinetics of Statins, Calcium Channel Blockers, and Beta-blockers

Lee Siew-Keah
1   M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Malaysia
,
Tan Hong Jie
1   M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Malaysia
,
Chua Ang-Lim
2   Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia
,
Liew Kai Bin
3   Faculty of Pharmacy, University of Cyberjaya, Cyberjaya, Malaysia
,
Chew Yik-Ling
4   Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
› Author AffiliationsThis work was supported by the Ministry of Higher Education (MOHE), Malaysia through Fundamental Research Grant Scheme (FRGS/1/2022/SKK10/UTAR/02/1), and Universiti Tunku Abdul Rahman, Malaysia through UTAR-Research Grant (IPSR/RMC/UTARRF/2021-C2/L08).
› Further Information
Also available at
    Permissions and Reprints

Abstract

Brewed green tea, green tea extract, and its primary active compound, epigallocatechin gallate, may interact with drugs and alter the drugʼs therapeutic effectiveness, ultimately leading to therapeutic failure or drug overdose. Several isolated reports have claimed that epigallocatechin gallate is the main active ingredient that causes these effects. While a few studies aimed to uncover evidence of epigallocatechin gallate-drug interactions, no study has thoroughly and collectively reviewed them. Epigallocatechin gallate is a potential cardioprotective agent used by many patients with cardiovascular diseases as a complementary medicine alongside conventional modern medications, either with or without the knowledge of their physicians. Therefore, this review focuses on the impact of concurrent epigallocatechin gallate supplementation on pharmacokinetics and pharmacodynamics of several commonly used cardiovascular drugs (statins, beta-blockers, and calcium channel blockers). The PubMed index was searched for key words related to this review, without year limit, and the results were analyzed for interactions of cardiovascular drugs with epigallocatechin gallate. This review concludes that epigallocatechin gallate increases systemic circulation of several statins (simvastatin, fluvastatin, rosuvastatin) and calcium channel blockers (verapamil), but decreases the bioavailability of beta-blockers (nadolol, atenolol, bisoprolol). Further studies on its clinical significance in affecting drug efficacy are required.

Key words

Theaceae - Camellia sinensis - green tea - EGCG - catechins - drug interactions - herb co-administration - drug efficacy - cardiovascular drugs


Publication History

Received: 04 April 2023

Accepted after revision: 15 June 2023

Accepted Manuscript online:
16 June 2023

Article published online:
14 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 World Health Organization. WHO Traditional Medicine Strategy: 2014–2023, Edition 2013. Accessed May 29, 2023 at: https://www.who.int/publications/i/item/9789241506096
    PubMed
  • 2 Che CT, George V, Ijinu TP, Pushpangadan P, Andrae-Marobela K. Chapter 2 – Traditional Medicine. In: Badal S, Delgoda R. eds. Pharmacognosy. Boston: Academic Press; 2017: 15-30
    Search in Google Scholar
  • 3 Builder PF. Introductory Chapter: Introduction to Herbal Medicine. Rijeka: IntechOpen; 2018
    Search in Google Scholar
  • 4 Babu PV, Liu D. Green tea catechins and cardiovascular health: An update. Curr Med Chem 2008; 15: 1840-1850
    CrossrefPubMedSearch in Google Scholar
  • 5 Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355: 134-138
    CrossrefPubMedSearch in Google Scholar
  • 6 Bhagwat S, Haytowitz DB. USDA Database for the Flavonoid Content of Selected Food. Release 3.2 (November 2015). Nutrient Data Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA. Accessed June 22, 2023 at: https://doi.org/10.15482/USDA.ADC/1324465
    CrossrefPubMed
  • 7 Mohd Sabri NA, Lee SK, Murugan DD, Ling WC. Epigallocatechin gallate (EGCG) alleviates vascular dysfunction in angiotensin II-infused hypertensive mice by modulating oxidative stress and eNOS. Sci Rep 2022; 12: 17633
    CrossrefPubMedSearch in Google Scholar
  • 8 EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Lambré C, Leblanc JC, Lillegaard IT, Moldeus P, Mortensen A, Oskarsson A, Stankovic I, Waalkens-Berendsen I, Woutersen RA, Andrade RJ, Fortes C, Mosesso P, Restani P, Arcella D, Pizzo F, Smeraldi C, Wright M. Scientific opinion on the safety of green tea catechins. EFSA J 2018; 16: e05239
    CrossrefPubMedSearch in Google Scholar
  • 9 Oketch-Rabah HA, Roe AL, Rider CV, Bonkovsky HL, Giancaspro GI, Navarro V, Paine MF, Betz JM, Marles RJ, Casper S, Gurley B, Jordan SA, He K, Kapoor MP, Rao TP, Sherker AH, Fontana RJ, Rossi S, Vuppalanchi R, Seeff LB, Stolz A, Ahmad J, Koh C, Serrano J, Low Dog T, Ko R. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep 2020; 7: 386-402
    CrossrefPubMedSearch in Google Scholar
  • 10 Norwegian Institute of Public Health. Safety Assessment on Levels of (−)-Epigallocatechin-3-Gallate (EGCG) in Green Tea Extracts Used in Food Supplements. Oslo: Norwegian Institute of Public Health; 2015
    Search in Google Scholar
  • 11 Ishii T, Ichikawa T, Minoda K, Kusaka K, Ito S, Suzuki Y, Akagawa M, Mochizuki K, Goda T, Nakayama T. Human serum albumin as an antioxidant in the oxidation of (−)-epigallocatechin gallate: Participation of reversible covalent binding for interaction and stabilization. Biosci Biotechnol Biochem 2011; 75: 100-106
    CrossrefPubMedSearch in Google Scholar
  • 12 Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Van Poel B, Pieters L, Vlietinck AJ, Berghe DV. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998; 61: 71-76
    CrossrefPubMedSearch in Google Scholar
  • 13 Mokra D, Joskova M, Mokry J. Therapeutic effects of green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) in relation to molecular pathways controlling inflammation, oxidative stress, and apoptosis. Int J Mol Sci 2023; 24: 340
    CrossrefPubMedSearch in Google Scholar
  • 14 Mokra D, Adamcakova J, Mokry J. Green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG): A time for a new player in the treatment of respiratory diseases?. Antioxidants (Basel) 2022; 11: 1566
    CrossrefPubMedSearch in Google Scholar
  • 15 Parn KW, Ling WC, Chin JH, Lee SK. Safety and efficacy of dietary epigallocatechin gallate supplementation in attenuating hypertension via its modulatory activities on the intrarenal renin-angiotensin system in spontaneously hypertensive rats. Nutrients 2022; 14: 4605
    CrossrefPubMedSearch in Google Scholar
  • 16 Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005; 81: 230S-242S
    CrossrefPubMedSearch in Google Scholar
  • 17 Nakagawa K, Miyazawa T. Absorption and distribution of tea catechin, (−)-epigallocatechin-3-gallate, in the rat. J Nutr Sci Vitaminol (Tokyo) 1997; 43: 679-684
    CrossrefPubMedSearch in Google Scholar
  • 18 Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS. 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: 1025-1032
    PubMedSearch in Google Scholar
  • 19 Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS, Hara Y. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev 2001; 10: 53-58
    PubMedSearch in Google Scholar
  • 20 Lin LC, Wang MN, Tseng TY, Sung JS, Tsai TH. Pharmacokinetics of (−)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J Agric Food Chem 2007; 55: 1517-1524
    CrossrefPubMedSearch in Google Scholar
  • 21 Chen L, Lee MJ, Li H, Yang CS. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab Dispos 1997; 25: 1045-1050
    PubMedSearch in Google Scholar
  • 22 Williamson G, Dionisi F, Renouf M. Flavanols from green tea and phenolic acids from coffee: critical quantitative evaluation of the pharmacokinetic data in humans after consumption of single doses of beverages. Mol Nutr Food Res 2011; 55: 864-873
    CrossrefPubMedSearch in Google Scholar
  • 23 Cerbin-Koczorowska M, Waszyk-Nowaczyk M, Bakun P, Goslinski T, Koczorowski T. Current view on green tea catechins formulations, their interactions with selected drugs, and prospective applications for various health conditions. Appl Sci 2021; 11: 4905
    CrossrefPubMedSearch in Google Scholar
  • 24 Knop J, Misaka S, Singer K, Hoier E, Muller F, Glaeser H, Konig J, Fromm MF. Inhibitory effects of green tea and (−)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein. PLoS One 2015; 10: e0139370
    CrossrefPubMedSearch in Google Scholar
  • 25 Albassam AA, Markowitz JS. An appraisal of drug-drug interactions with green tea (Camellia sinensis). Planta Med 2017; 83: 496-550
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Chung JH, Choi DH, Choi JS. Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats. Biopharm Drug Dispos 2009; 30: 90-93
    CrossrefPubMedSearch in Google Scholar
  • 27 Choi JS, Burm JP. Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats. Arch Pharm Res 2009; 32: 1721-1725
    CrossrefPubMedSearch in Google Scholar
  • 28 Li C, Choi JS. Effects of epigallocatechin gallate on the bioavailability and pharmacokinetics of diltiazem in rats. Pharmazie 2008; 63: 815-818
    PubMedSearch in Google Scholar
  • 29 Shin SC, Choi JS. Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats. Anticancer Drugs 2009; 20: 584-588
    CrossrefPubMedSearch in Google Scholar
  • 30 Kim TE, Shin KH, Park JE, Kim MG, Yun YM, Choi DH, Kwon KJ, Lee J. Effect of green tea catechins on the pharmacokinetics of digoxin in humans. Drug Des Devel Ther 2018; 12: 2139-2147
    CrossrefPubMedSearch in Google Scholar
  • 31 Deng F, Tuomi SK, Neuvonen M, Hirvensalo P, Kulju S, Wenzel C, Oswald S, Filppula AM, Niemi M. Comparative hepatic and intestinal efflux transport of statins. Drug Metab Dispos 2021; 49: 750-759
    CrossrefPubMedSearch in Google Scholar
  • 32 Filppula AM, Hirvensalo P, Parviainen H, Ivaska VE, Lönnberg KI, Deng F, Viinamäki J, Kurkela M, Neuvonen M, Niemi M. Comparative hepatic and intestinal metabolism and pharmacodynamics of statins. Drug Metab Dispos 2021; 49: 658-667
    CrossrefPubMedSearch in Google Scholar
  • 33 Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L. The effect of green tea on simvastatin tolerability. Ann Intern Med 2008; 149: 286-287
    CrossrefPubMedSearch in Google Scholar
  • 34 Yang W, Zhang Q, Yang Y, Xu J, Fan A, Yang CS, Li N, Lu Y, Chen J, Zhao D, Aa J, Chen X. Epigallocatechin-3-gallate decreases the transport and metabolism of simvastatin in rats. Xenobiotica 2017; 47: 86-92
    CrossrefPubMedSearch in Google Scholar
  • 35 Scripture CD, Pieper JA. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet 2001; 40: 263-281
    CrossrefPubMedSearch in Google Scholar
  • 36 Misaka S, Abe O, Sato H, Ono T, Shikama Y, Onoue S, Yabe H, Kimura J. Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy volunteers. Eur J Clin Pharmacol 2018; 74: 601-609
    CrossrefPubMedSearch in Google Scholar
  • 37 Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: A review of the pharmacology and clinical effectiveness in cardiovascular disease. Clin Med Insights Cardiol 2012; 6: 17-33
    CrossrefPubMedSearch in Google Scholar
  • 38 Kim TE, Ha N, Kim Y, Kim H, Lee JW, Jeon JY, Kim MG. Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers. Drug Des Devel Ther 2017; 11: 1409-1416
    CrossrefPubMedSearch in Google Scholar
  • 39 Zeng W, Hu M, Lee HK, Wat E, Lau CBS, Ho CS, Wong CK, Tomlinson B. Effect of green tea extract and soy isoflavones on the pharmacokinetics of rosuvastatin in healthy volunteers. Front Nutr 2022; 9: 850318
    CrossrefPubMedSearch in Google Scholar
  • 40 Tracy TS, Korzekwa KR, Gonzalez FJ, Wainer IW. Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Br J Clin Pharmacol 1999; 47: 545-552
    CrossrefPubMedSearch in Google Scholar
  • 41 Zisaki A, Miskovic L, Hatzimanikatis V. Antihypertensive drugs metabolism: An update to pharmacokinetic profiles and computational approaches. Curr Pharm Des 2015; 21: 806-822
    CrossrefPubMedSearch in Google Scholar
  • 42 AA Pharma Inc.. Product Monograph: Nadolol. Accessed February 15, 2023 at: https://www.aapharma.ca/downloads/en/PIL/2016/Nadolol_pm.pdf
    PubMed
  • 43 Misaka S, Knop J, Singer K, Hoier E, Keiser M, Muller F, Glaeser H, Konig J, Fromm MF. The nonmetabolized beta-blocker nadolol is a substrate of OCT1, OCT2, MATE1, MATE2-K, and P-glycoprotein, but not of OATP1B1 and OATP1B3. Mol Pharm 2016; 13: 512-519
    CrossrefPubMedSearch in Google Scholar
  • 44 Tan HJ, Ling WC, Chua AL, Lee SK. Oral epigallocatechin gallate reduces intestinal nadolol absorption via modulation of Oatp1a5 and Oct1 transcriptional levels in spontaneously hypertensive rats. Phytomedicine 2021; 90: 153623
    CrossrefPubMedSearch in Google Scholar
  • 45 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: 1936
    CrossrefPubMedSearch in Google Scholar
  • 46 Wang ZY, Li YQ, Guo ZW, Zhou XH, Lu MD, Xue TC, Gao B. ERK1/2-HNF4α axis is involved in Epigallocatechin-3-gallate inhibition of HBV replication. Acta Pharmacol Sin 2020; 41: 278-285
    CrossrefPubMedSearch in Google Scholar
  • 47 Shan Y, Zhang M, Wang T, Huang Q, Yin D, Xiang Z, Wang X, Sheng J. Oxidative tea polyphenols greatly inhibit the absorption of atenolol. Front Pharmacol 2016; 7: 192
    CrossrefPubMedSearch in Google Scholar
  • 48 Bakheit AH, Ali R, Alshahrani AD, El-Azab AS. Chapter Two – Bisoprolol: A Comprehensive Profile. In: Al-Majed AA. editor Profiles of drug substances, excipients and related methodology. Massachusetts: Academic Press; 2021: 51-89
    Search in Google Scholar
  • 49 Zeng W, Lao S, Guo Y, Wu Y, Huang M, Tomlinson B, Zhong G. The influence of EGCG on the pharmacokinetics and pharmacodynamics of bisoprolol and a new method for simultaneous determination of EGCG and bisoprolol in rat plasma. Front Nutr 2022; 9: 907986
    CrossrefPubMedSearch in Google Scholar
  • 50 Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS. Hepatotoxicity of high oral dose (−)-Epigallocatechin-3-gallate in mice. Food Chem Toxicol 2010; 48: 409-416
    CrossrefPubMedSearch in Google Scholar
  • 51 Isbrucker RA, Edwards JA, 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: 636-650
    CrossrefPubMedSearch in Google Scholar
  • 52 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
    CrossrefPubMedSearch in Google Scholar