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

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.

Biological properties and therapeutic effects of plant-derived nanovesicles

“…Since GDNs blocked the assembly and activation of NLRP3 inflammasome, these NVs represent a new promising class of NLRP3 inflammasome inhibitors. Exosome-like nanoparticles from six mushrooms presented various effects on the NLRP3 inflammasome in BMDM [42]. Interestingly, NVs from Shiitake mushrooms (SMNs), at a concentration range Wheat grass WDNs promote proliferation and exert anti-apoptotic effects on HDF (primary human dermal fibroblasts), HUVEC (human endothelial vascular endothelial cells), and HaCaT (human keratinocytes), induce tube branching in HUVEC, and increase collagen type I expression in HaCaT as both protein and mRNA [69] BMDCs: bone marrow-derived dendritic cells; BMDM: bone marrow-derived macrophages; HO-1: heme oxygenase-1; IL: interleukin; Nrf2: nuclear factor (erythroid-derived 2)-like 2; NVs: nanovesicles; LPS: lipopolysaccharide; ROS: reactive oxygen species; TNF: tumor necrosis factor.…”

“…In alternative to weighing, the yield of PDNVs can be measured by a zeta-sizer. For instance, among the mushrooms tested, oyster mushroom-derived exosome-like nanoparticles had the lowest yield of 2.3 ± 1.5 × 10 11 /g, whereas white button mushroom-derived PDNVs had the highest yield of 8.1 ± 1.6 × 10 11 /g [ 42 ].…”

“…The size distribution range was from 30 to 100 nm in diameter. Seven edible mushrooms, including white bottom, Swiss brown, king oyster, shiitake, white beech, brown beech, and oyster, were characterized for the presence of exosome-like nanoparticles that were 100–140 nm in range by a NanoSight NS300 instrument and presented a sphere-shaped morphology by SEM [ 42 ] ( Figure 2e ). Finally, apple-derived NPs (APNPs) were shown to have a size ranging from 100 to 400 nm by measurement with a qNano using a NP200 nanopore at a 47 mm stretch [ 67 ].…”

Strawberry-Derived Exosome-Like Nanoparticles Prevent Oxidative Stress in Human Mesenchymal Stromal Cells

“…They contain metabolites, proteins, lipids, RNAs, miRNAs, mRNAs, and DNAs and can transfer their cargo to recipient cells, playing a fundamental role as extracellular messengers to mediate cell–cell communication [ 3 ]. The critical role played by EVs in the mediation of cell–cell communication has been identified both in health and disease and in bacterial, fungal, and animal kingdoms [ 4 , 5 , 6 , 7 , 8 ]. An increasing number of studies have shown the existence of plant-derived nanosized particles, the characteristics of which resemble those of mammalian exosomes [ 9 , 10 , 11 , 12 ].…”

Blueberry-Derived Exosome-Like Nanoparticles Counter the Response to TNF-α-Induced Change on Gene Expression in EA.hy926 Cells

“…Among them, exosomes are nanometer-sized vesicles in a range of 30-100 nm, present in many biological fluids of different organisms [3]. Previous studies have identified and reported the existence of exosome-like nanoparticles (ELNs) in plants [4], fruits [5], and very recently also in mushrooms [6].…”