Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD), has emerged as the leading cause of liver failure and related death. Currently, no medication is specifically approved to treat NAFLD or NASH. Here we report that oral administration of honey vesicle-like nanoparticles (H-VLNs) to naturally aged mice protects the liver from NASH development. H-VLNs are dominantly taken up by Kupffer cells in the liver and suppress hepatic chronic inflammation and further development of fibrosis and nodule formation in aged mice. Besides their reported anti-inflammasome function, H-VLNs are found to inhibit the transcriptional activities of C-JUN and nuclear factor-kappa B (NF-κB). MicroRNAs miR5119 and miR5108 and phenolic compound luteolin in H-VLNs are identified in suppressing both the C-JUN and NF-κB pathways. Collectively, oral intake of H-VLNs represents a promising new user-friendly modality to prevent the development of NASH. Oral administered H-VLNs alleviated inflammation, fibrosis development, and nodule formation in naturally aged liver. Their bioactive cargos inhibited the activities of the NLRP3 inflammasome, NF-κB, and c-Jun in Kupffer cells/macrophages. [Display omitted]