Tea leaf exosome-like nanoparticles (TELNs) improve oleic acid-induced lipid metabolism by regulating miRNAs in HepG-2 cells

Abstract Tea is a widely consumed beverage globally, but the tea industry faces a significant waste management challenge. In this study, we developed tea leaf exosome-like nanoparticles (TELNs) with an average size of 274 ± 24.7 nm and a zeta potential of -20.6 ± 0.78 mV, using polyethylene glycol (PEG) 6000 precipitation followed by ultracentrifugation. Structural analysis confirmed that TELNs are composed of lipids, proteins, and RNAs. In vitro assays on HepG-2 cells revealed that TELNs are non-toxic at concentrations up to 300 µg/mL and can be efficiently internalized. TELNs exhibited significant antioxidant capacity and were able to significantly ameliorate H 2 O 2 -induced oxidative stress, increase the viability and reduce the accumulation of ROS in Hepg-2 cells. Notably, TELNs significantly alleviated OA-induced lipid metabolic disorders and hepatocellular injury. Further molecular analysis revealed that TELNs downregulated the expression of miR-21-5p, miR-17-3p, and miR-107, leading to the upregulation of their target genes PPARα, CYP7A1, and CPT-1A, which contributed to the improvement of lipid metabolism. This study is the first to demonstrate the lipid metabolism regulation potential of TELNs, providing new insights into their underlying mechanisms and helping to develop new therapeutic strategies for lipid metabolism-related diseases. Furthermore, it expands the scope of tea use and helps to reuse tea residues. Graphical Abstract