Protective role of shiitakemushroom-derived exosome-like nanoparticles in d-galactosamine and lipopolysaccharide-induced acute liver injury inmice

Baolong Liu, Yizhu Lu, Xingyi Chen, Philma Glora Muthuraj, Xingzhi Li, Mahesh Pattabiraman, Janos Zempleni, Stephen D. Kachman, Sathish Kumar Natarajan, Jiujiu Yu

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantially inhibited NLRP3 inflammasome activation by preventing inflammasome formation in primary macrophages. S-ELNs also suppressed the secretion of interleukin (IL)-6, as well as both protein and mRNA levels of the Il1b gene. Remarkably, pre-treatment with S-ELNs protected mice from GalN/LPS-induced acute liver injury. Therefore, S-ELNs, identified as potent new inhibitors of the NLRP3 inflammasome, represent a promising class of agents with the potential to combat FHF.

Original languageEnglish (US)
Article number477
JournalNutrients
Volume12
Issue number2
DOIs
StatePublished - Feb 2020

Keywords

  • Exosomes
  • Fulminant hepatic failure
  • Inflammation
  • NLRP3 inflammasome
  • Nanoparticles
  • Shiitake mushrooms

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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