The role of mitochondrial dysfunction in the protective effect of ginger derived extracellular vesicles on hepatic stellate cells against cytotoxicity.

Abstract

Previous studies have shown that ginger-derived extracellular vesicles (Gin-EVs) can alleviate alcohol-induced liver injury. It remained unknown and needs to be further verified that whether the vesicles has therapeutic potential to alleviate the progression of liver fibrosis. Moreover, the relevant mechanisms need to be further studied. Herein, we provide evidence that Gin-EVs effectively interact with human hepatic stellate cells (LX-2), offering protection against carbon tetrachloride (CCL4) or lipopolysaccharides (LPS)-induced liver fibrosis. The treatment with Gin-EVs was observed to mitigate fibrosis and enhance cell viability in LX-2 cells exposed to CCL4 or LPS. Mechanistically, Gin-EVs counteracted mitochondrial dysfunction by restoring mitochondrial dynamics imbalance characterized by enhanced fusion and reduced fission events while promoting mitochondrial biogenesis, thereby potentially preventing fibrotic processes in LX-2 cells. Collectively, the findings highlight the direct cytoprotective effects of Gin-EVs on LX-2 cells and suggest their promising role as a therapeutic option for hepatic fibrosis.