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

Carrier-free oleanolic acid nanoparticles (OA-NM) formed via anti-solvent exchange. • OA-NM self-assembly was driven by hydrogen bonding and hydrophobic interactions. • OA-NM was internalized mainly via clathrin-mediated endocytosis. • OA-NM improved lipid metabolism and insulin resistance in 3 T3-L1 adipocytes. • OA-NM exert stronger anti-inflammatory effects in RAW264.7 macrophages. 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 3 T3-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. Download: Download high-res image (205KB) Download: Download full-size image