Whey Protein Peptides Self-Assembled Nanoparticles with Intrinsic Cholesterol Esterase Inhibition Enhance Stigmasterol Bioaccessibility and Hypocholesterolemic Effects.

Background

Stigmasterol (St) holds promise as a natural cholesterol-lowering agent, yet its poor aqueous solubility and low bioaccessibility severely constrain its application in functional foods.

Methods

In this study, we exploited whey protein peptides (WPP) with intrinsic cholesterol esterase (CEase) inhibitory activity to construct St-loaded self-assembled nanoparticles. Subsequently, we investigated its physicochemical properties and formation mechanism and evaluated its hypocholesterolemic activity through animal experiments.

Results

Driven by non-covalent hydrophobic and hydrogen-bonding interactions, the optimized St-loaded WPP nanoparticles (St@WPP) ((234.47 ± 1.36) nm) achieved a high encapsulation efficiency (EE) of 74.73% ± 2.19%. This nano-encapsulation markedly improved St dispersibility and storage stability, and significantly elevated its bioaccessibility from 9.00% ± 0.14% to 19.41% ± 0.69% after simulated gastrointestinal digestion. St@WPP administration effectively ameliorated dyslipidemia, as evidenced by reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), which may be associated with reduced intestinal cholesterol availability and increased fecal cholesterol content. Moreover, St@WPP alleviated hepatic steatosis, attenuated systemic inflammation, and rebalanced gut microbiota architecture.

Conclusions

Collectively, the WPP shell functions as a delivery carrier that improves the water solubility and bioaccessibility of St, thereby broadening its potential for application in low-fat or aqueous-based food systems. The resulting St@WPP exhibits notable cholesterol-lowering activity, positioning it as a promising functional food ingredient with potential benefits for cholesterol management.