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Antimalarial agent artesunate protects Concanavalin A-induced autoimmune hepatitis in mice by inhibiting inflammatory responses
- 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.
- Subjects :
- Male
0301 basic medicine
Pyrrolidines
p38 mitogen-activated protein kinases
Artesunate
Autoimmune hepatitis
Pharmacology
Protective Agents
Toxicology
p38 Mitogen-Activated Protein Kinases
Proinflammatory cytokine
Antimalarials
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
NF-KappaB Inhibitor alpha
Pyrrolidine dithiocarbamate
Thiocarbamates
Interferon
Concanavalin A
medicine
Animals
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Hepatitis
Mice, Inbred BALB C
biology
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
Interleukin-17
JNK Mitogen-Activated Protein Kinases
NF-kappa B
General Medicine
medicine.disease
Artemisinins
Hepatitis, Autoimmune
IκBα
030104 developmental biology
Liver
chemistry
030220 oncology & carcinogenesis
Mitogen-activated protein kinase
Immunology
biology.protein
business
Signal Transduction
medicine.drug
Subjects
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