Ginseng-derived exosome-like nanovesicles protect against liver fibrosis by regulating TIMP2 pathways and gut dysbiosis

Abstract

Metabolic dysfunction-associated fatty liver disease (MASLD) and alcohol-associated liver disease (ALD) are prevalent chronic liver diseases that can progress to steatohepatitis, fibrosis, cirrhosis, and ultimately liver failure. Here, we demonstrated that oral administration of GNVs provided substantial protection against liver injury and fibrosis in MASLD and ALD mouse models. In a Western-style high-fat diet-induced MASLD model and a chronic binge alcohol-induced ALD model, GNVs treatment significantly reduced gut leakiness by restoring intestinal junctional complex proteins and rebalancing the gut microbiome. GNVs attenuated hepatic lipid accumulation, oxidative stress and fibrogenic markers. GNV treatment downregulated the fibrosis-associated tissue inhibitor of metalloproteinase-2 (TIMP2) pathway in hepatic stellate cells, which is linked to enhanced matrix degradation and reduced fibrogenesis. GNVs prevent MASLD- and ALD-associated gut barrier dysfunction and liver fibrosis through modulation of the gut-liver axis and the TIMP2 pathway. Edible GNVs represent a novel, multifaceted therapeutic strategy for managing chronic liver diseases.

Keywords

Ginseng-derived exosome-like nanovesicles / Liver fibrosis / Gut dysbiosis / Gut leakiness / Gut-liver axis / Tissue inhibitor of metalloproteinase-2 (TIMP2)

Conflicts of interest

The authors declare that there is no conflicts of interest.

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (project number RS-2024-00340542). This work was also supported in part (to B.J.S.) by the Intramural Fund of National Institute of Alcohol Abuse and Alcoholism. This research was supported by the 2022 research grant from the Korean Society of Ginseng. This study was conducted as Yejin Sim's Master's thesis (2023) at Andong National University and has been revised for submission.

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2025.101105. The figures and tables with "S" before the serial number are included in the Supplementary material.

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