Alcohol intake is a major risk factor for the pathogenesis of alcoholic liver diseases. Accumulating evidence suggests that green tea protects against alcoholic liver injury; however, the underlying mechanisms remain unclear. The present study investigated the role of endothelial nitric oxide synthase (eNOS) in the protective effects of green tea against alcohol-induced liver injury and inflammation. Ethanol was intragastrically administered to male C57BL/6 mice once a day, and the mice were allowed free access to green tea infusion or water for two weeks. We assessed the plasma levels of alanine aminotransferase and aspartate aminotransferase, hepatic contents of thiobarbituric acid reactive substances, malondialdehyde and triglyceride and hepatic mRNA expression of pro-inflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6). Our results showed that compared with water alone, green tea infusion markedly reduced liver damage, hepatic oxidative stress, hepatic lipid accumulation and inflammatory response. Green tea infusion also significantly reduced hepatic nuclear factor-κB expression and its downstream inflammatory mediators (inducible nitric oxide synthase and cyclooxygenase-2) mRNA levels in ethanol-treated mice. Additionally, green tea infusion significantly activated hepatic phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt), which are associated with the upregulation of phosphorylated eNOS expression and the increase of plasma nitric oxide levels in ethanol-treated mice. Furthermore, the protective effects of green tea infusion were considerably inhibited by the eNOS inhibitor N^G-nitro-L-arginine methyl ester in ethanol-treated mice. In conclusion, our study demonstrated that the protective effects of green tea infusion on alcohol-induced liver injury and inflammation involve the modulation of the PI3K/AKT/eNOS pathway.

Tea, a beverage consumed worldwide, has proven anti-hyperglycemic effects in animal models. Better efficacies of tea beverages are frequently associated with high-dose levels, whose safety attracts considerable attention. Based on the inherent nature of tea catechin oxidation, fresh tea leaves are manufactured into diverse tea types by modulating the oxidation degree of catechins. The present study aimed to assess various tea types for their safety properties and anti-hyperglycemic effects. Mice were allowed free access to tea infusion (1:30, w/v) for one week, and the rare smoked tea caused salient adverse reactions, including hepatic and gastrointestinal toxicities; meanwhile, the widely-consumed green and black teas, unlike the rare yellow tea, suppressed growth in fast-growing healthy mice. When mice were fed a high-fat diet and allowed free access to tea infusion (1:30, w/v) for 25 days, only yellow tea significantly reduced blood glucose. Therefore, various teas showed different safety profiles as well as anti-hyperglycemic efficacy strengths. To achieve an effective and safe anti-hyperglycemic outcome, yellow tea, which effectively suppressed high-fat diet-induced early elevation of hepatic thioredoxin-interacting protein, is an optimal choice.

We have demonstrated previously that melatonin attenuates hepatotoxicity triggered by high doses of (−)-epigallocatechin-3-gallate (EGCG) in mice. The current work investigated the influence of melatonin on the oncostatic activity of EGCG in two cancer cell lines, wherein melatonin induced an opposite response of p21. In human tongue cancer TCA8113 cells, melatonin-induced p21 and EGCG-mediated formation of quinoproteins were positively associated with the oncostatic effects of melatonin and EGCG. Melatonin-stimulated an increase in p21 which was correlated with a pronounced nuclear translocation of thioredoxin 1 and thioredoxin reductase 1, both of which are known to induce p21 via promoting p53 trans-activation. Melatonin did not influence the EGCG-mediated increase of quinoprotein formation nor did EGCG impair melatonin-induced p21 up-regulation. Co-treatment with both agents enhanced the cell-killing effect as well as the inhibitory activities against cell migration and colony formation. It is known that p21 also plays a powerful anti-apoptotic role in some cancer cells and confers these cells with a survival advantage, making it a target for therapeutic suppression. In human hepatocellular carcinoma HepG2 cells, melatonin suppressed p21 along with the induction of pro-survival proteins, PI3K and COX-2. However, EGCG prevented against melatonin-induced PI3K and COX-2, and melatonin probably sensitized HepG2 cells to EGCG cytotoxicity via down-regulating p21, Moreover, COX-2 and HO-1 were significantly reduced only by the co-treatment, and melatonin aided EGCG to achieve an increased inhibition on Bcl2 and NFκB. These events occurring in the co-treatment collectively resulted in an enhanced cytotoxicity. In addition, the co-treatment also enhanced the inhibitory activities against cell migration and colony formation. Overall, the results gathered from these two cancer cell lines with a divergent p21 response to melatonin show that the various oncostatic activities of melatonin and EGCG together are more robust than each agent alone, suggesting that they may be useful partners in fighting cancer.