Inflammatory liver diseases present a significant public health problem. Green tea polyphenols (GTPs) have a myriad of health benefits in animals and humans, including alleviating of hepatic inflammation; however, the underlying mechanisms are complicated and remain unclear. The current study investigated the preventive effects and mechanism of GTPs on lipopolysaccharide (LPS)-induced inflammatory liver injury in mice. The ICR mice received intragastric GTPs once per day for 7 consecutive days prior to LPS stimulation (15 mg kg⁻¹, intraperitoneally) and liver damage and oxidative stress, pro-inflammatory cytokines, and the hepatic nuclear factor-κB (NF-κB) and Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes were observed. Our results showed that GTP supplementation significantly reduced LPS-induced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic malondialdehyde (MDA) levels; and LPS-induced reduction of glutathione (GSH) levels and total superoxide dismutase (T-SOD) activities was drastically improved by GTP pretreatment. GTP supplementation significantly reduced plasma contents and hepatic mRNA levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α, compared with LPS-treated mice which did not receive GTP treatment. In addition, the production of cytokines, such as IL-1β, IL-18, IL-6, and TNF-α in mice livers, and acute-phase response (plasma levels of nitric oxide and C-reactive protein) were also decreased following GTP pre-treatment. Furthermore, GTPs reduced LPS-induced hepatic NF-κB signaling and NLRP3 inflammasome activation. GTPs exert protective effects against inflammatory liver injury by regulating NF-κB signaling and the NLRP3 inflammasome activation. Our findings suggest that dietary GTP supplementation may be an adjunctive prevention and treatment for acute liver injury-associated inflammation.

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.

Dietary EGCG maintains the intestinal immune homeostasis, which might play a role in preventing systemic inflammation and NAFLD.