Serum albumin acted as an effective carrier to improve the stability of bioactive flavonoid.

The health-improving functions of bioactive flavonoids in vitro and in vivo are often limited by their low stability, which could be counteracted by the application of proteins as carriers of flavonoids. Clarification of the mechanism of protein-ligand interaction is crucial for the encapsulation of bioactive components. Herein, common plasma proteins [i.e., bovine serum albumin (BSA), human serum albumin (HSA), human immunoglobulin G (IgG) and fibrinogen (FG)] were compared for their binding characteristics to quercetin, the main component of flavonoids in human diet, in the absence and presence of free Cu (an accelerator for flavonoids' instability) using multi-spectroscopic and computational methods. As a flexible open structure of proteins, both BSA and HSA were found to be the most promising carriers for quercetin and Cu with an affinity on the order of 10 M. HSA-diligand complex (i.e., HSA-quercetin-Cu) was successfully generated when both quercetin and Cu were added to the HSA solution. The stability and free radical scavenging activity of bioactive quercetin during incubation was promoted in the HSA-diligand complex relative to quercetin-Cu complex. Quercetin/Cu system could induce the formation of reactive oxygen species such as hydrogen peroxide (HO) and hydroxide radical (·OH), which were significantly suppressed upon HSA binding. Consistently, the cytotoxicity of the quercetin/Cu system to endothelial cells was reduced in the HSA-diligand complex. These results demonstrate the possibility of developing serum albumin-based carriers for the protection of bioactive flavonoids in their nutritional application.