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Chem Biol Interact. 2017 Aug 25;274:116-123. doi: 10.1016/j.cbi.2017.07.012. Epub 2017 Jul 13.

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

Author information

1
School of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
2
School of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address: jingui_li@163.com.

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.

KEYWORDS:

Artesunate; Concanavalin A-induced hepatitis; MAPK; Mouse; NF-κB

PMID:
28712788
DOI:
10.1016/j.cbi.2017.07.012
[Indexed for MEDLINE]

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