Identification of Exosome-Like Nanoparticles as a New Bioactive Component in Honey

Abstract

Abstract Objectives To investigate whether honey, as a medicinal food, contain exosome-like nanoparticles (ELNs). Methods Honey was diluted in phosphate-buffered saline and subjected to sequential centrifugation followed by ultracentrifugation. ELNs were obtained from honey. Such ELNs were characterized in detail by electron microscopy analysis and biomolecule omics analysis. The anti-inflammatory functions of these honey-derived ELNs (H-ELNs) were studied in primary macrophages and experimentally induced acute liver injury in mice. Results H-ELNs were membrane-enclosed nanoparticles composed of lipids, proteins, and RNAs. These nanoparticles specifically hindered assembly and activation of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, which is a critical pro-inflammatory enzyme complex in the innate immune system. H-ELNs protected mice from acute inflammation and liver damage in the experimentally induced acute liver injury. microRNA miR-4057 in H-ELNs was found to potently inhibit activation of the NLRP3 inflammasome. Conclusions H-ELNs were identified as a new bioactive component in honey and these nanoparticles demonstrated potent anti-inflammatory function in vitro and in vivo. This finding opens a new avenue for studying honey, a medicinal food since ancient times. Funding Sources This work was supported by the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) and the National Institutes of Health (NIH) National Institute for General Medical Science (NIGMS).