Melatonin attenuates (-)-epigallocatehin-3-gallate-triggered hepatotoxicity without compromising its downregulation of hepatic gluconeogenic and lipogenic genes in mice

Dongxu Wang, Yaqing Wei, Taotao Wang, Xiaochun Wan, Chung S. Yang, Russel J. Reiter, Jinsong Zhang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

(-)-Epigallocatehin-3-gallate (EGCG), a major constituent of green tea, can ameliorate metabolic syndrome at least in part through reducing gluconeogenesis and lipogenesis. Green tea extracts, of which EGCG is a key constituent, have been used for weight loss in humans. A potential adverse effect of high-dose EGCG or green tea extracts is hepatotoxicity. Melatonin, an endogenous antioxidant with a high safety profile, is effective in preventing various types of tissue damage. The current study investigated the influence of melatonin on EGCG-triggered hepatotoxicity and EGCG-downregulated hepatic genes responsible for gluconeogenesis and lipogenesis in mice. We found that (i) melatonin extended survival time of mice intoxicated with lethal doses of EGCG; (ii) melatonin ameliorated acute liver damage and associated hepatic Nrf2 suppression caused by a nonlethal toxic dose of EGCG; (iii) melatonin reduced subacute liver injury and hepatic Nrf2 activation caused by lower toxic doses of EGCG; and (iv) melatonin did not compromise the action of pharmacological doses of EGCG in downregulating a battery of hepatic genes responsible for gluconeogenesis and lipogenesis, including G6Pc, PEPCK, FOXO1α, SCD1, Fasn, leptin, ACCα, ACCβ, GAPT, and Srebp-1. Taken together, these results suggest that the combination of EGCG and melatonin is an effective approach for preventing potential adverse effects of EGCG as a dietary supplement for metabolic syndrome alleviation and body weight reduction.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalJournal of pineal research
Volume59
Issue number4
DOIs
StatePublished - Nov 1 2015

Keywords

  • (-)-Epigallocatehin-3-gallate
  • gluconeogenesis
  • hepatotoxicity
  • lipogenesis
  • melatonin

ASJC Scopus subject areas

  • Endocrinology

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