Journal
JOURNAL OF PINEAL RESEARCH
Volume 59, Issue 4, Pages 497-507Publisher
WILEY-BLACKWELL
DOI: 10.1111/jpi.12281
Keywords
(-)-Epigallocatehin-3-gallate; gluconeogenesis; hepatotoxicity; lipogenesis; melatonin
Categories
Funding
- National Natural Science Foundation of China [31170648]
- Tea Project of Anhui Provincial Agriculture Committee
- Anhui Major Demonstration Project for Leading Talent Team on Tea Chemistry and Health
- Funds of Anhui Provincial Science and Technology Department [1306c083018]
- Anhui Agricultural University and Foundation of AHAU [XKTS2013017]
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(-)-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, FOXO1, SCD1, Fasn, leptin, ACC, ACC, 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.
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