Generation of a Bovine Serum Albumin–Diligand Complex for the Protection of Bioactive Quercetin and Suppression of Heme Toxicity

Abstract

As an abundant protein in milk and blood serum, bovine serum albumin (BSA) contains various sites to bind a lot of bioactive components, generating BSA− monoligand complex. Demonstration of the interaction between BSA and bioactive components (such as heme, flavonoids) is important to develop effective carrier for the protection of bioactive ligands and to reduce cytotoxicity of heme. Herein, the bindings of BSA to quercetin and/or heme were investigated by multispectroscopic and molecular docking methods. The fluorescence of protein was significantly quenched by both quercetin and heme in a static mode (i.e., generation of BSA−ligand complex). Although quercetin had lower affinity to protein than heme, the interactions of both compounds with protein did locate in site I (i.e., subdomain IIA). BSA−diligand complex was successfully generated after the coaddition of quercetin and heme. The cytotoxicity of free heme to endothelial cells was reduced in the BSA−diligand complex relative to that of heme or BSA− monoligand complex, while the stability of bioactive quercetin was promoted in the complex relative to free flavonoid. The complex provided a better inhibition on the cytotoxicity of heme than BSA−monoligand complex, in which the copresence of quercetin played a vital role.

Bovine Serum Albumin as a Potential Carrier for the Protection of Bioactive Quercetin and Inhibition of Cu(II) Toxicity

“…Ions and water molecules were removed from the original X-ray structure of BSA. Quercetin and/or free Cu­(II) were docked to the crystal structure of the protein by AutoDock 4.0 software, as described previously. ,,, The best docked model with the lowest docking energy was chosen to represent the most favorable binding modes.…”

“…The absorption at 374 nm was a characteristic peak of bioactive quercetin and could represent the stability of this flavonoid. ,,,, In order to investigate the stability of this component, the absorbance of free quercetin, quercetin with BSA, and quercetin with the BSA–Cu­(II) complex was measured at 374 nm, at different time intervals.…”

“…It is of great interest to develop effective carriers that can simultaneously encapsulate and protect several bioactive components. ,,,, Our previous study has demonstrated the generation of the BSA–diligand complex with carbon nanotubes and quercetin for the protection of bioactive components and inhibition of nanotubes’ cytotoxicity . Although the generation of the BSA–monoligand complex is widely reported, ,− the formation of a BSA–multiligand complex with bioactive flavonoids and free Cu­(II) is still scarcely investigated.…”

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

“…Serum albumins are known to function as a carrier for many bioactive ligands in a 1:1 stoichiometry, eg, lipids, but also binding heme and thereby contributing to reducing heme-cytotoxicity, and, by binding flavonoids like quercetin, enhancing its stability. 78 A monomeric and dimeric variant are depicted in Fig. 2.…”

The affinity of histamine to serum albumin: Capillary electrophoresis‐frontal analysis and in‐silico molecular docking approaches

“…Since bovine serum albumin (BSA) is the closest molecule to human serum albumin and can be obtained economically in experimental studies, it is used as a model in drug-albumin affinity studies. The affinity between BSA and many drug molecules such as antipsychotic drugs [6], anti-tumour drugs [7], and small drug molecules such as ibuprofen, warfarin, phenytoin, and sulfanilamide [8], as well as many natural bioactive substances or food additives [9][10][11], has been studied.…”