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

Baolong Liu; Phuong Linh Nguyen; Han Yu; Xingzhi Li; Huiren Wang; Tram Gia Bao Nguyen; Prakash Kumar Sahoo; Meghna Sur; Jay Reddy; Sarah Sillman; Stephen D Kachman; Bara Altartouri; Guoqing Lu; Sathish Kumar Natarajan; Mahesh Pattabiraman; Jiujiu Yu

doi:10.1016/j.apsb.2024.05.002

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

Acta Pharm Sin B. 2024 Aug;14(8):3661-3679. doi: 10.1016/j.apsb.2024.05.002. Epub 2024 May 10.

Authors

Baolong Liu^{1

2}, Phuong Linh Nguyen^{1

3}, Han Yu^{1

3}, Xingzhi Li¹, Huiren Wang¹, Tram Gia Bao Nguyen¹, Prakash Kumar Sahoo¹, Meghna Sur⁴, Jay Reddy⁴, Sarah Sillman⁴, Stephen D Kachman⁵, Bara Altartouri⁶, Guoqing Lu⁷, Sathish Kumar Natarajan¹, Mahesh Pattabiraman⁸, Jiujiu Yu^{1

3}

Affiliations

¹ Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
² Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
³ Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA.
⁴ School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁵ Department of Statistics, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁶ Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
⁷ Department of Biology, University of Nebraska Omaha, Omaha, NE 68182, USA.
⁸ Department of Chemistry, University of Nebraska-Kearney, Kearney, NE 68849, USA.

Abstract

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.

Keywords: Aging; Exosomes; Extracellular vesicles; Honey; Inflammation; Nanoparticles; Non-alcoholic steatohepatitis; microRNAs.