Soyasaponin II protects against acute liver failure through diminishing YB-1 phosphorylation and Nlrp3-inflammasome priming in mice
| Autor: | Shenhai Gong, Guiming Chen, Hongwei Zhou, Zhanguo Liu, Haihua Luo, Junhao Wang, Yong Jiang, Fangzhao Wang, Peng Chen, Teng Wang, Chenyang Huang, Qifan Zhang, Lei Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Lipopolysaccharide Inflammasomes Interleukin-1beta Anti-Inflammatory Agents Medicine (miscellaneous) Priming (immunology) Pharmacology Protective Agents Immunofluorescence YB-1 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine soyasaponin II NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans Oleanolic Acid Pharmacology Toxicology and Pharmaceutics (miscellaneous) Messenger RNA medicine.diagnostic_test Chemistry Macrophages Binding protein Inflammasome Promoter acute liver failure Liver Failure Acute Saponins Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology Liver Nlrp3-inflammasome Phosphorylation 030211 gastroenterology & hepatology Y-Box-Binding Protein 1 Transcription Factors Research Paper medicine.drug |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|