(P30-038-23) Honey Exosome-Like Nanoparticles Protect Aged Liver From Non-Alcoholic Steatohepatitis

Objectives: To investigate the potential health benefits of honey exosome-like nanoparticles (H-ELNs) in aging-related morbidities.

Methods: Honey was subjected to the ultracentrifugation method to isolate H-ELNs. Such ELNs were weekly administered to 1-year-old C57BL/6J mice for one year through oral gavage. After one-year treatment, the mice were sacrificed and their liver samples were subjected to histopathological and biochemical analyses. The bioactive compounds in H-ELNs were screened to identify the responsible molecules for the hepatoprotective functions of H-ELNs.

Results: Oral administration of H-ELNs in naturally aged mice protected the liver from development of non-alcoholic steatohepatitis (NASH). The inflammation, fibrosis, and nodule formation in aged livers were suppressed by H-ELNs. H-ELNs were dominantly taken up by macrophages in the liver and inhibited the transcriptional activities of c-Jun and nuclear factor-kappaB (NF-kB), besides their reported anti-inflammasome function. MicroRNAs miR5110 and miR5108, and phenolic compound luteolin in H-ELNs were identified in suppressing both c-Jun and NF-kB pathways.

Conclusions: H-ELNs represent a promising new agent with the potential to prevent the development of NASH. NASH often leads to the progression of life-threatening liver cirrhosis and hepatocellular carcinoma, but there is no specific licensed medication to treat NASH. H-ELNs could serve as a feasible and user-friendly approach to protect the liver in general and especially in elderly NASH patients.

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 of Diabetes and Digestive and Kidney Diseases (NIDDK).