Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl₄)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl₄-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl₄ model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl₄-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl₄-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c⁺ dendritic cells into the liver tissues of CCl₄-treated mice. These results indicated that eckol has the protective effect on CCl₄-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.
Keywords: acute liver injury; apoptosis; dendritic cells; eckol; inflammation; oxidative stress.