Pomegranate-derived exosome-like nanovesicles ameliorate high-fat diet-induced nonalcoholic fatty liver disease via alleviating mitochondrial dysfunction

Plant-derived exosome-like nanovesicles carry a variety of bioactive substances and have multiple health benefits. Pomegranate (Punica granatum) is a popular fruit with hepatoprotective effects. However, the effects of pomegranate-derived exosome-like nanovesicles (PENs) on nonalcoholic fatty liver disease (NAFLD) are still unknown. Here, PENs were successfully isolated and characterized, and found to be internalized by HepG2 cells. Interestingly, PENs survived gastrointestinal environment and ameliorated lipid accumulation as well as mitochondrial dysfunction in palmitic acid (PA)-treated HepG2 cells. Importantly, oral administration of PENs accumulated in the liver of mice and effectively alleviated high-fat diet (HFD)-induced NAFLD by improving mitochondrial function, as evidenced by improvements of ATP content, mitochondrial complex I activity and oxidative stress. Moreover, PENs restored SIRT3/SOD2 signaling and improved SOD2 activity in the liver of HFDfed mice. These findings provide new mechanistic insights into pomegranate's hepatoprotection and demonstrate the therapeutic potential of PENs for NAFLD.

Automated summary

Plant-derived exosome-like nanovesicles from pomegranate (PENs) demonstrated therapeutic potential for nonalcoholic fatty liver disease (NAFLD) by improving mitochondrial function and reducing lipid accumulation. In cell experiments, PENs were internalized by HepG2 cells and ameliorated palmitic acid-induced lipid accumulation and mitochondrial dysfunction. In mouse experiments, oral administration of PENs accumulated in the liver and effectively alleviated NAFLD induced by high-fat diet, with improvements in mitochondrial function and antioxidant capacity. These findings provide new mechanistic insights into pomegranate's hepatoprotective effects and highlight the therapeutic potential of PENs for NAFLD.