Antimalarial agent artesunate protects Concanavalin A-induced autoimmune hepatitis in mice by inhibiting inflammatory responses

摘要

The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-kappa B (NF-kappa B) and mitogen activated protein kinase (MAPK) signaling pathways. However, ARS pretreatment notably inhibited Con A-induced liver injury with remarkable reduction of liver enzymes, and dramatically suppressed the expression of inflammatory cytokines including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and IL-17, and increased anti-inflammatory cytokines IL-10. In line with cytokines, the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogenactivated protein kinases (p38), nuclear factor-kappa Ba (I kappa B alpha) and NF-kappa B p65 was also significantly inhibited by ARS pretreatment. As a contrast, the specific inhibitor of NF-kappa B pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as ARS on phosphorylation of p65 and I kappa Ba, and serum levels of aminotransferases. Taken together, these data highlight that ARS has facilitating to make a better understanding of ARS against acute autoimmune hepatitis, and indicating a promising therapy candidate for autoimmune hepatitis. (C) 2017 Elsevier B.V. All rights reserved.