Weak Binding of Epigallocatechin to α-Lactalbumin Greatly Improves Its Stability and Uptake by Caco-2 Cells.

Improving the stability and bioavailability of catechins is of great importance. Epigallocatechin (EGC), the major catechin in green tea, is a potent antioxidant with numerous attributed health benefits. However, the low permeability and stability limit its enrichment in the diet for preventive medicine. In this study, we explored the interaction of EGC and α-lactalbumin by spectroscopic, thermodynamic, and crystallographic methods. The isothermal titration calorimetry experiments elucidated that α-lactalbumin binds to EGC at a ratio of 1:1 with a low affinity of (4.01 ± 0.11) × 105 M-1. A crystal structure solved at a high resolution (1.2 Å) provided direct evidence for the weak interaction between EGC and α-lactalbumin at an atomic level. The novel binding site was discovered at the exterior surface of α-lactalbumin for the first time, supporting a new binding behavior. Consequently, our results demonstrated that the binding of α-lactalbumin to EGC could protect EGC against light-induced, thermal-induced, and pH-induced damage. More importantly, the formed complex has better bioaccessibility than unbound EGC, which was approved by a cell absorption experiment. Such research is beneficial for designing protein-based nanocarriers for polyphenols.