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

Authors :
ShaoJie Yin
MingJiang Liu
Xin Zhao
YangYang Wu
AnYuan Wang
Jin-Gui Li
Source :
Chemico-Biological Interactions. 274:116-123
Publication Year :
2017
Publisher :
Elsevier BV, 2017.

Abstract

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-κB (NF-κB) 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)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, 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 mitogen-activated protein kinases (p38), nuclear factor-κBα (IκBα) and NF-κB p65 was also significantly inhibited by ARS pretreatment. As a contrast, the specific inhibitor of NF-κB pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as ARS on phosphorylation of p65 and IκBα, 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.

Details

ISSN :
00092797
Volume :
274
Database :
OpenAIRE
Journal :
Chemico-Biological Interactions
Accession number :
edsair.doi.dedup.....1294cd20a6c555f63c13a9f518175c6c
Full Text :
https://doi.org/10.1016/j.cbi.2017.07.012