Interaction of Curcumin with β-Lactoglobulin—Stability, Spectroscopic Analysis, and Molecular Modeling of the Complex

Abstract

Curcumin (diferuloyl methane) is the physiologically and pharmacologically active component of turmeric (Curcuma longa L.). Solubility and stability of curcumin are the limiting factors for realizing its therapeutic potential. β-Lactoglobulin (βLG), the major whey protein, can solubilize and bind many small hydrophobic molecules. The stability of curcumin bound to βLG in solution is enhanced 6.7 times, in comparison to curcumin alone (in aqueous solution). The complex formation of curcumin with βLG has been investigated employing spectroscopic techniques. βLG interacts with curcumin at pH 7.0 with an association constant of 1.04 ± 0.1 × 10(5) M(-1) to form a 1:1 complex at 25 °C. Entropy and free energy changes for the interaction derived from the van't Hoff plot are 18.7 cal mol(-1) K(-1) and -6.8 kcal mol(-1) at 25 °C, respectively; the interaction is hydrophobic in nature. The interaction of βLG with curcumin does not affect either the conformation or the state of association of βLG. Competitive ligand binding measurements, binding studies with denatured βLG, effect of pH on the curcumin-βLG interaction, Förster energy transfer measurements, and molecular docking studies suggest that curcumin binds to the central calyx of βLG. These binding studies have prompted the preparation and encapsulation of curcumin in βLG nanoparticles. Nanoparticles of βLG prepared by desolvation are found to encapsulate curcumin with >96% efficiency. The solubility of curcumin in βLG nanoparticle is significantly enhanced to ∼625 μM in comparison with its aqueous solubility (30 nM). Nanoparticles of βLG, by virtue of their ability to enhance solubility and stability of curcumin, may fit the choice as a carrier molecule.

Curcumin Prevents Aggregation in α-Synuclein by Increasing Reconfiguration Rate

“…By measuring binding at various temperatures, we determined the enthalpy (⌬H ϭ Ϫ7.9 kcal/mol) and entropy (⌬S ϭ Ϫ0.0081 kcal/mol/K) of binding, indicating that binding is enthalpically driven and suggesting that it is due to non-hydrophobic interactions. These observations are similar to previous reports of binding of curcumin to proteins such as ␣-1-casein (14), ␤-lactoglobulin (15), and FtsZ (16). The binding profiles for the two loops investigated here were the same, indicating that the Trp and Cys mutations do not significantly affect curcumin binding.…”

Comparison of the colloidal stability, bioaccessibility and antioxidant activity of corn protein hydrolysate and sodium caseinate stabilized curcumin nanoparticles

“…Additionally, the average particle size of Cur NPs stabilized by other native proteins (e.g. zein, b-lactoglobulin) was *100 nm or higher (Patel et al 2010;Sneharani et al 2010). Therefore, the size of Cur NPs in CPH is obviously smaller than the native protein-based Cur NPs.…”

“…This notion could be strongly supported by a large number of related investigations (Chen . 2015a, b;Pan et al 2013;Prasad et al 2014;Sneharani et al 2010), where Cur all exhibited good chemical stability after the NPs fabrication. The chemical stability of Cur at a high temperature (75°C) was also investigated (Fig.…”

Bionanomaterials from Plant Sources

“…Another nanotechnologic approach targeting the therapeutic potential of curcumin, which is not realized due to its poor stability and low water solubility, was to bind it to β-lactoglobulin, a whey protein known for binding small hydrophobic molecules [ 12 ]. Hybrid nanoparticles, prepared by desolvation, encapsulated curcumin with >96 % effi ciency and increased the stability of curcumin 6.7 times.…”