ABSTRACT
The interaction of curcumin (Cur) with human angiogenin (hAng), a potent blood vessel inducer responsible for angiogenesis is found to change following encapsulation within the ß-cyclodextrin (ßCD) cavity. The enhanced bioavailability and increase in the binding stoichiometry of hAng:Cur-ßCD (1:2) leads to increased affinity, hence an increase in the association constant. The altered mode of hAng inhibition of Cur from a non-competitive (KI = 23.7 ± 2.2 µM) to a mixed type (KI = 19.8 ± 1.4 µM), after encapsulation provides an insight into interaction patterns. Isothermal titration calorimetry (ITC) experiments indicate the formation of multiple favorable non-covalent interactions (also confirmed by docking studies), which implies negative enthalpy changes (-ΔHo) and restriction in the dynamic mobility of the free protein molecule resulting in a very less positive entropy change (TΔSo). This leads to a medium magnitude for the spontaneous free energy change associated with the interaction/binding process. The spontaneity of binding indicates a more favorable value for the Cur-ßCD (ΔGo = -7.75 kcal/mol) compared to Cur (ΔGo = -7.49 kcal/mol). In vivo studies also demonstrate the anti-angiogenic effect of Cur/Cur-ßCD confirmed by the significant decrease in blood vessel density and branching index.
