TY - JOUR
T1 - Protective role of shiitakemushroom-derived exosome-like nanoparticles in d-galactosamine and lipopolysaccharide-induced acute liver injury inmice
AU - Liu, Baolong
AU - Lu, Yizhu
AU - Chen, Xingyi
AU - Muthuraj, Philma Glora
AU - Li, Xingzhi
AU - Pattabiraman, Mahesh
AU - Zempleni, Janos
AU - Kachman, Stephen D.
AU - Natarajan, Sathish Kumar
AU - Yu, Jiujiu
N1 - Publisher Copyright:
© 2020 by the authors.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Exosomes
KW - Fulminant hepatic failure
KW - Inflammation
KW - NLRP3 inflammasome
KW - Nanoparticles
KW - Shiitake mushrooms
UR - http://www.scopus.com/inward/record.url?scp=85079651923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079651923&partnerID=8YFLogxK
U2 - 10.3390/nu12020477
DO - 10.3390/nu12020477
M3 - Article
C2 - 32069862
AN - SCOPUS:85079651923
SN - 2072-6643
VL - 12
JO - Nutrients
JF - Nutrients
IS - 2
M1 - 477
ER -