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Inhibitory Effects of Dietary Exosome-Like Nanoparticles on NLRP3 Inflammasome Activation
Dietary-derived exosome-like nanoparticles (ELNs) have received increasing attention in the fields of interspecies communication, drug delivery and disease treatment. We are interested in understanding how the dietary-derived ELNs affect the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome activation. The NLRP3 inflammasome, composed of NLRP3, apoptotic speck protein containing a caspase recruitment domain (ASC), and caspase-1, is an important component in the innate immune system. Dysregulated activation of the NLRP3 inflammasome has been implicated in the pathogenesis of many inflammatory diseases, such as type-2 diabetes, Alzheimer’s disease, and gout. Targeting the NLRP3 inflammasome may have therapeutic potential in treating these diseases. In our study, different dietary-derived ELNs were examined for their effects on NLRP3 inflammasome activation. Among them, ginger and honey-derived ELNs were identified to suppress all downstream events of NLRP3 inflammasome activation, including caspase-1 autocleavage, interleukin (IL)-1β and IL-18 release, and pyroptotic cell death. Remarkably, honey-derived ELNs were found to alleviate inflammation in mice and protect mice from D-galactosamine and lipopolysaccharide-induced acute liver injury. In addition, ginger and honey-derived ELNs were characterized in detail. Nanoparticle Tracking Analysis (NTA) was applied to determine their sizes and yields. Consistent with the size of most dietary ELNs, ginger-derived ELNs were approximately 130 nm in diameter while honey-derived ELNs were approximately 150 nm in diameter. Electron microscopy (EM) techniques revealed that both ginger and honey-derived ELNs were dispersed individual nanoparticles with sphere-shaped morphology. Additionally, ginger and honey-derived ELNs carry lipids, proteins, and small-sized RNAs. Taken together, our study suggests ginger and honey-derived ELNs as new potent agents that inhibit NLRP3 inflammasome activation, which may provide new therapeutic strategies to curb or manage the NLRP3 inflammasome-mediated diseases.
Chen, Xingyi, "Inhibitory Effects of Dietary Exosome-Like Nanoparticles on NLRP3 Inflammasome Activation" (2020). ETD collection for University of Nebraska - Lincoln. AAI27832170.