A Novel Strategy for Oxidative Damage: Lycopene Nanoformulations Improve Redox Homeostasis and Gut Microbiota Composition in Mice.

Lycopene use in water-based foods is limited by poor dispersibility and low stability. Here, two food-grade glyco-carrier lycopene nanoformulations were prepared using dextran (lyc-dextran) or d-mannose (lyc-mannose) and evaluated in vitro and in vivo. Both formed near-spherical nanoparticles (190-252 nm) with negative ζ-potentials (≈-26 to -28 mV) and predominantly noncovalent assembly; encapsulation efficiencies were 70.0% and 68.8%, respectively. Under thermal/photo stress (4-60°C; dark vs. 4000 lx), both nanoformulations increased lycopene retention; at 60°C/4000 lx, 300-min retention was 40.78% for free lycopene versus ∼70%-72% (lyc-dextran) and ∼62%-67% (lyc-mannose). The nanoformulations showed strong chemical antioxidant capacity and alleviated H2O2-induced oxidative injury in HUVECs (lower malondialdehyde [MDA], higher catalase [CAT]/superoxide dismutase [SOD]/glutathione peroxidase [GSH-Px], with changes in Nrf2/SIRT3-related proteins). In d-galactose-treated mice, interventions were associated with reduced hepatic MDA, elevated antioxidant enzyme activities, a lower AST/ALT ratio, and attenuated liver injury, accompanied by formulation-associated shifts in gut microbiota structure. Overall, food-grade glyco-nanocarriers enhance lycopene stability and antioxidant-related performance, supporting their potential for lycopene-based nano-functional foods.