Hypolipidemic Effects of Yellow Wine Lees Protein and its Peptides: Extraction, Mechanism, and Functional Food Potential

Yellow wine lees, a by-product of Chinese yellow rice wine fermentation, are underutilized and pose environmental risks. This study extracted yellow wine lees protein (YWLP) using alkaline extraction and ultrasonic treatment, exploring its hypolipidemic activity and mechanism. YWLP exhibited antioxidant properties, pancreatic lipase (PL) and cholesterol esterase (ChE) inhibition, bile acid salt binding, and inhibition of cholesterol micellar solubilization. In a high-fat HepG2 cell model, YWLP (62.5-2000 μg/mL) significantly reduced (P < 0.05) intracellular lipid levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglycerides (TG), while increasing high-density lipoprotein (HDL-C). Ultrafiltration revealed the < 3 kDa fraction as having the most significant lipid-lowering effect, while lipid-lowering peptides (SRGFGF, SWCRC, and FNLPR) were identified through LC-MS/MS and molecular docking. In vitro experiments confirmed the optimal lipid-lowering effect of SWCRC, with IC₅₀ values of (1.153 ± 0.14) mmol/L for PL and (6.587 ± 0.228) mmol/L for ChE. Ultraviolet-visible spectroscopy, fluorescence spectroscopy, and molecular dynamics revealed its mechanism, confirming significant affinity toward both enzymes. Meanwhile, a Caenorhabditis elegans model was used to test lipid inhibition at different concentrations SWCRC (125-2000 μmol/L), and the results showed that lipids were significantly reduced in the SWCRC group compared with the model group (P < 0.05). These results suggest YWLP could serve as a natural lipid-lowering agent in functional foods, offering a sustainable use for yellow wine lees.