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Open AccessArticle

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

1
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
2
Department of Chemistry, University of Nebraska-Kearney, Kearney, NE 68849, USA
3
Department of Statistics, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(2), 477; https://doi.org/10.3390/nu12020477
Received: 23 December 2019 / Revised: 8 February 2020 / Accepted: 10 February 2020 / Published: 13 February 2020
(This article belongs to the Section Phytochemicals and Human Health)
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. View Full-Text
Keywords: shiitake mushrooms; exosomes; nanoparticles; NLRP3 inflammasome; inflammation; fulminant hepatic failure shiitake mushrooms; exosomes; nanoparticles; NLRP3 inflammasome; inflammation; fulminant hepatic failure
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MDPI and ACS Style

Liu, B.; Lu, Y.; Chen, X.; Muthuraj, P.G.; Li, X.; Pattabiraman, M.; Zempleni, J.; Kachman, S.D.; Natarajan, S.K.; Yu, J. Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice. Nutrients 2020, 12, 477.

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