Soyasaponin II protects against acute liver failure through diminishing YB-1 phosphorylation and Nlrp3-inflammasome priming in mice.

Abstract:

:Acute liver failure is characterized by the rapid development of liver dysfunction and remarkably high mortality. Accumulating evidence suggests that soyasaponin possesses potential anti-inflammatory activities. Here, we aimed to investigate the potential role of soyasaponin II in acute liver failure and establish the underlying mechanism. Methods: Lipopolysaccharide/D-galactosamine (LPS/GalN) was employed to induce acute liver failure. We applied liquid chromatography and mass spectrometry (LC/MS) to characterize the changes of soyasaponin II levels in the cecal content and liver. Transcriptomics and proteomics analysis were used to evaluate the functional molecule mediated by soyasaponin II in macrophages. Results: LPS/GalN administration markedly decreased fecal and hepatic soyasaponin II levels. Soyasaponin II treatment protected mice against LPS/GalN induced acute liver injury. Additionally, soyasaponin II markedly diminished Y-Box Binding Protein 1 (YB-1) phosphorylation and nuclear translocation, Nlrp3 inflammasome priming, and interleukin 1β (Il-1β) production in macrophages. Phosphorylated YB-1 could activate Nlrp3 mRNA transcription by binding the promoter region. Finally, immunofluorescence analysis showed elevated p-YB-1 nuclear translocation in macrophages of acute liver failure patients compared to controls. Conclusion: Our data shows that soyasaponin II which serves as a novel inhibitor for YB-1 phosphorylation and Nlrp3 inflammasome priming could protect mice against LPS/GalN induced acute liver failure.

journal_name

Theranostics

journal_title

Theranostics

authors

Wang F,Gong S,Wang T,Li L,Luo H,Wang J,Huang C,Zhou H,Chen G,Liu Z,Zhang Q,Jiang Y,Chen P

doi

10.7150/thno.40128

subject

Has Abstract

pub_date

2020-02-03 00:00:00

pages

2714-2726

issue

6

issn

1838-7640

pii

thnov10p2714

journal_volume

10

pub_type

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