Pomegranate‐Derived Exosome‐Like Nanovesicles Containing Ellagic Acid Alleviate Gut Leakage and Liver Injury in MASLD

ABSTRACT Exosome‐like nanovesicles derived from plants (PENs) harbor a spectrum of bioactive compounds, including proteins, lipids, nucleic acids (such as miRNAs and mRNAs), offering therapeutic advantages for a variety of diseases. This investigation assesses the utility of pomegranate‐derived exosome‐like nanovesicles (PNVs) in both preventing and treating complications such as liver damage and increased intestinal permeability found in Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD). Utilizing Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA), we successfully isolated PNVs and characterized their structural properties. Upon administration in a live model, these nanovesicles were efficiently distributed to critical organs, including the liver and intestines, demonstrating biocompatibility by avoiding toxic effects. Remarkably, these vesicles were enriched with ellagic acid, known for its strong antioxidant capabilities. In a controlled MASLD mouse study, treatment with PNVs significantly lowered serum endotoxin levels, reinforced intestinal barrier functions, and altered the gut microbiota profile favorably. Furthermore, the application of PNVs reduced oxidative stress and the presence of fibrosis markers in the liver to normal levels. These results indicate that PNVs could be a viable option for addressing MASLD, enhancing intestinal integrity, reducing liver injury, and diminishing fibrosis through the modulation of the gut‐liver axis.