Several polyphenol compounds commonly found in plant foods provide health benefits that promote their applications in food and pharmaceutical fields. The co-loading of proteins can improve the biological activity and synergy of combined polyphenols. Herein, multi-spectroscopic techniques and molecular docking were employed to investigate the interactions of native/heat treated β-lactoglobulin (β-LG/H-β-LG) with (−)-epicatechin gallate (ECG) and/or piceatannol (PIC). Furthermore, the synergistic antioxidant activity and cytotoxicity of ECG and PIC were demonstrated. The loading of β-LG/H-β-LG protected the antioxidant activity of ECG and PIC in the delivery systems and enhanced their cytotoxicity, stability, and bioaccessibility. Compared to the corresponding complexes, the nanoparticles of β-LG/H-β-LG had a greater impact on the functional properties and synergistic effects of ECG and PIC. The experimental results may provide a theoretical basis for the practical application of ECG and PIC co-loaded by H-β-LG, particularly H-β-LG nanoparticles in the food and pharmaceutical industries.
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