Egg yolk phospholipid peptides as dual-functional nanocarriers for curcumin: Enhanced hypolipidemic effects and mechanism.

Egg yolk phospholipid peptide (EYPP) possesses a unique amphiphilic structure; however, its dual role as a functional nanocarrier in mediating lipid metabolism, which encompasses both delivery capacity and intrinsic bioactivity, remains poorly characterized. In this study, EYPP loaded with curcumin (Cur) co-assembled nanocomplexes (EYPP-Cur) were constructed, and their lipid-lowering efficacy and underlying molecular mechanisms were evaluated using a high-fat diet (HFD)-induced mouse model. Virtual screening combined with molecular docking was employed to identify key bioactive peptide motifs within EYPP. Results showed that EYPP encapsulated Cur via hydrophobic interactions to form monodisperse, stable particles (mean size ∼190 nm, PDI < 0.3), which significantly improved Cur's aqueous solubility. In vivo experiments demonstrated that EYPP-Cur outperformed single-component treatments (EYPP or Cur alone) in suppressing body weight gain, reducing serum lipid levels (total cholesterol, low-density lipoprotein cholesterol), and ameliorating hepatic steatosis, indicating a distinct enhanced effect. Mechanistic investigations revealed that EYPP-Cur reshaped cholesterol metabolic homeostasis primarily by upregulating the expression of CYP7A1 and LDLR, and inhibiting HMGCR activity, while also effectively alleviating oxidative stress and inflammation. Additionally, the screened EYPP-derived peptide fragment LEF was verified to bind stably to LDLR and cholesterol esterase via hydrogen bonding and electrostatic interactions. Collectively, EYPP functions not only as a superior nanocarrier to enhance the solubility of hydrophobic nutrients but also as an intrinsic bioactive agent with lipid metabolism-regulating properties. This study provides a novel strategy for the development of dual-functional foods integrating both delivery and therapeutic capacities.