Self-assembled nanoparticles of oleanolic acid as a potential functional food ingredient with improved dispersibility and metabolic modulation activity.

Oleanolic acid (OA) is a plant-derived pentacyclic triterpenoid with anti-obesity and anti-inflammatory activities, but its poor solubility limits bioavailability. In this study, self-assembled OA nanoparticles (OA-NM) were prepared via an anti-solvent method to enhance dispersibility and efficacy. OA-NM exhibited uniform spherical morphology (∼228 nm), good stability, and supramolecular reorganization driven mainly by hydrophobic interactions and hydrogen bonding. Its cellular uptake occurred primarily via clathrin-mediated endocytosis. Compared with free OA, OA-NM showed lower cytotoxicity and enhanced bioactivity. In 3T3-L1 adipocytes, OA-NM reduced lipid accumulation, suppressed adipogenic gene expression, improved mitochondrial function, and restored insulin signaling. In LPS-stimulated RAW264.7 macrophages, OA-NM inhibited M1 polarization, promoted M2 transition, and suppressed NF-κB-mediated inflammation. Overall, self-assembly significantly improves the functional performance of OA, highlighting OA-NM as a promising strategy to enhance the utilization of hydrophobic dietary bioactives for metabolic health applications.