Abstract
This study aimed to evaluate whether (-)-epigallocatechin-3-gallate (EGCG) alleviates hepatic responses to lipopolysaccharide (LPS)-induced inflammation and oxidation. Isolated bovine hepatocytes and BALB/c mice were used for LPS challenge and EGCG pretreatment experiments in vitro and in vivo. LPS-challenged (6 μg/mL) hepatocytes exhibited increased levels of NF-κB (p65 and IκBα) and MAPK (p38, ERK, JNK) phosphorylation as well as increased binding activity of p65 to target pro-inflammatory gene promoters, and these effects were suppressed by pretreatment with 50 μM EGCG. Moreover, the reduction in Nrf2 signaling and antioxidant enzyme activities induced by LPS stimulation were reversed upon EGCG treatment. In vivo experiments demonstrated the protective role of EGCG in response to GalN/LPS-induced mortality and oxidative damage. Together, our results suggest that EGCG is hepatoprotective via inhibition of MAPK/NF-κB signaling and activation of the Nrf2 cascade. This information might help design strategies for counteracting hepatitis in ruminants and monogastric animals.