AbstractBACKGROUNDMany foods contain proteins and polyphenols, but there is a poor understanding of the nature of the inhibitory effect of protein on the biologic activity of polyphenols. The inhibitory mechanism of the food protein lactoferrin on the antibacterial activity of oligomeric ellagitannin oenothein B (OeB) was investigated using fluorescence quenching, isothermal titration calorimetry (ITC), circular dichroism (CD) measurement and molecular docking.RESULTSThe antibacterial activity of OeB against Staphylococcus aureus was inhibited by lactoferrin, which was retained at about 60%. An interaction study revealed that an interaction occurred between OeB and lactoferrin. Thermodynamic analyses indicate that the binding process was spontaneous, and the main driving forces were based on electrostatic interactions that contributed to a high interaction affinity between OeB and lactoferrin. Furthermore, CD spectra provided insights into conformational changes of lactoferrin. Finally, molecular docking analysis provided a visual representation of a single binding site where OeB interacted with specific amino acid residues located at the active site of lactoferrin. In particular, due to the unique macrocyclic structure and rigid ring structure of OeB, a small number of hydroxyl groups in the rigid structure of OeB interacted with the amino acid of lactoferrin while most of the phenolic hydroxyl groups were not associated with lactoferrin.CONCLUSIONOur study provides a theoretical basis for the use of OeB as an antibacterial substance that can be used in nutraceuticals and pharmaceutical products. © 2020 Society of Chemical Industry