Design, fabrication and molecular dynamics simulations of luteolin pickering emulsion using phosphorylated and succinylated lactoferrin nanocomplex.
Guan Tianzhu, Li Ning, Feng Yining, Gao Ya, Xue Wei, Rao Shengqi, Ma Changyang, Kang Wenyi
Abstract
Chemically modified protein-based nanocomplexes are widely used as food-grade carriers, but their molecular mechanisms remain unclear. This study developed Pickering emulsions (PEs) composed of phosphorylated (PLF) or succinylated (SLF) lactoferrin (LF) complexed with luteolin (LUT) via a pH-driven method, integrating experimental and computational approaches. SLF-LUT PEs showed superior physicochemical properties, including smaller droplet sizes, encapsulation efficiency up to 80% under neutral conditions, and enhanced storage stability at pH 8 over 30 days. SLF-LUT also significantly inhibited lipid oxidation, with reduced primary and secondary oxidation products. Multi-ligand docking and 100 ns molecular dynamics simulations revealed that LUT binds multiple flaxseed oil fatty acids within lactoferrin's hydrophobic pocket, positioning it for radical scavenging at the oil-water interface. The LF-LUT complex remained stable in a lipid-rich environment, with key residues (LEU320, PRO251, SER252) critical for stabilization. Network pharmacology further linked these interactions to antioxidant pathways (KEAP1/NRF2, FoxO, AGE-RAGE). These findings highlight the potential of nanocomplex-based oil-in-water PEs for delivering hydrophobic bioactives in food and pharmaceutical applications.
Key Findings
- SLF-LUT Pickering emulsions exhibited superior physicochemical properties including smaller droplet sizes and up to 80% encapsulation efficiency under neutral pH.
- SLF-LUT significantly inhibited lipid oxidation, reducing primary and secondary oxidation products, indicating strong antioxidant activity.
- Molecular dynamics simulations identified stable binding of luteolin within lactoferrin's hydrophobic pocket, with key residues critical for stabilization and linked to antioxidant pathways including KEAP1/NRF2.
Clinical Significance
This study demonstrates the potential of lactoferrin-luteolin nanocomplexes to enhance antioxidant delivery and stability, which may be leveraged to mitigate oxidative stress-related damage in food and pharmaceutical applications.
Citation
Guan Tianzhu, Li Ning, Feng Yininget al.. Design, fabrication and molecular dynamics simulations of luteolin pickering emulsion using phosphorylated and succinylated lactoferrin nanocomplex. NPJ science of food. 2026-Jul-10.