Effect of green tea and its polyphenols on mouse liver ☆ Ibrahim G. Saleh a,b , Zulfiqar Ali a , Naohito Abe a , Floyd D. Wilson c , Farid M. Hamada b , Mohamed F. Abd-Ellah b , Larry A. Walker a,d , Ikhlas A. Khan a,e,f , Mohammad K. Ashfaq a, ⁎ a National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA b Department of Pharmacology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt c Mississippi Veterinary Research and Diagnostic Laboratory, College of Veterinary Medicine, Mississippi State University, Pearl, MS 39208, USA d Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA e Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA f Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11557, Saudi Arabia article info abstract Article history: Received 11 May 2013 Accepted in revised form 16 July 2013 Available online 26 July 2013 Increased consumption of green tea (GT) without enough scientific data has raised safety concerns. Epigallocatechin 3-gallate (EGCG) is the most prominent polyphenol of GT that has antioxidant activity. However, higher doses of EGCG have been shown to cause liver injury. This study was initiated to determine the effect of GT extracts in a mouse model. We also investigated the effects of EGCG in normal and health-compromised mice. Different doses of GT fractions and EGCG were administered for 5 days to mice. Also, a single dose of lipopolysaccharide (LPS) was combined with EGCG in order to investigate its effect in the presence of fever. Plasma ALT and ALP levels were determined along with liver histopathology. Combining a single high IG dose of EGCG with a single IP dose of LPS initiated liver injury. Furthermore, repeated administration of high IG doses of EGCG showed mild liver injury, but it was augmented under febrile conditions induced by LPS. This study confirms the safety of reasonable consumption of GT over a short term. However, it highlights a caution that high doses of EGCG can lead to mild liver injury, and this may be markedly enhanced under febrile conditions. © 2013 The Authors. Published by Elsevier B.V. All rights reserved. Keywords: Green tea EGCG LPS Liver Mouse Histopathology 1. Introduction Tea is one of the most popular beverages consumed worldwide. It is obtained from the plant Camellia sinensis, as green, black, or oolong tea [1]. Green tea (GT) is favored in Japan, China and the Middle East; therefore, initial research on its benefits was carried out in these countries [2,3]. Green and black teas are processed differently. Green tea is prepared from freshly harvested leaves that are steamed to prevent fermentation, yielding a dry, stable product. Fresh tea leaves are rich in the flavanol group of polyphenols known as catechins which may constitute up to 30% of the dry leaf weight. The most prominent catechins are: epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate (EGCG). Other polyphenols include flavonols and their glycosides such as chlorogenic acid, coumarylquinic acid, and one unique to tea, theogallin (3-galloylquinic acid). Green tea leaves contain three main components which affect human health: xanthic bases (caffeine and theophylline), essential oils and especially, polyphenolic compounds. Caffeine is present at an average level of 3% along with very small amounts of the other common methylxanthines: theobromine and theophylline. The amino acid theanine (5-Nethylglutamine) is also unique to tea [4]. Green tea has been considered a healthy beverage since ancient times. Traditional Chinese medicine has recommended Fitoterapia 90 (2013) 151–159 Abbreviations: Fr., Fraction; GT, Green tea; Fig., Figure; IG, Intragastric; IP, Intraperitoneal; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; EGCG, Epigallocatechin-3-gallate; LPS, Lipopolysaccharide. ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License, which permits non- commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. ⁎ Corresponding author at: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Room 2047, University, MS 38677, USA. Tel.: +1 662 915 1577; fax: +1 662 915 7062. E-mail address: mkashfaq@olemiss.edu (M.K. Ashfaq). 0367-326X/$ – see front matter © 2013 The Authors. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.fitote.2013.07.014 Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote