Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-kappaB and IFN-gamma/STAT1 pathways.
BACKGROUND
Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury.


RESULTS
C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappaB and IFN-gamma/STAT1.


CONCLUSIONS
In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-kappaB and IFN-gamma/STAT1 signaling pathways.
Xu
Yan
Y
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
Feng
Dechun
D
Wang
Ying
Y
Lin
Shuting
S
Xu
Lingyun
L
D000818:Animals; D003208:Concanavalin A / Q000633:toxicity; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008517:Phytotherapy; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D027561:Salvia miltiorrhiza / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D007166:Immunosuppressive Agents; D016328:NF-kappa B; D010616:Phenanthrenes; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; C024894:tanshinone II A sodium sulfonate; D007371:Interferon-gamma