Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

Authors

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

ORCID IDs

https://orcid.org/0000-0002-2982-4690

https://orcid.org/0000-0001-7491-8592

Document Type

Article

Date of this Version

2-13-2020

Citation

2020 by the authors

Comments

Nutrients 2020, 12, 477; doi:10.3390/nu12020477 www.mdpi.com/journal/nutrients

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.