The protective effects of Shikonin on lipopolysaccharide/D-galactosamine-induced acute liver injury via inhibiting MAPK and NF-kappa B and activating Nrf2/HO-1 signaling pathways

摘要

Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities. However, the protective effects and mechanism of SHK on lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced acute liver injury remain unclear. In this study, LPS/D-GalN caused acute liver injury by intraperitoneal injection. SHK was administrated for 1 h. Then, LPS/D-GalN was given to C57BL/6 mice for 3 h. Our results showed that SHK treatment distinctly decreased serum TNF-alpha, IL-1 beta,IL-6 and IFN-gamma inflammatory cytokine production, reduced serum ALT, AST, hepatic MPO and ROS production levels, and tissue histology harmful effects, inhibited JNK1/2, ERK1/2, p38 and NF-kappa B (p65) phosphorylation, and suppressed IkBa phosphorylation and degradation. Furthermore, our research showed that SHK could dramatically increase SOD and GSH production, as well as reduce ROS production, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation. These results showed that SHK exerted antiinflammatory activity, which was associated to the inhibition of inflammatory production via downregulation of the MAPK and NF-kappa B signaling pathways, and anti-oxidative effects were connected with GSH and SOD activation through up-regulation of the Nrf2/HO-1 signaling pathways.