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Alpha-2-macroglobulin (α₂M) is large glycoprotein present in the body fluids of vertebrates. It is an antiproteinase that inhibits a broad spectrum of proteases without the direct blockage of the protease active site. Curcumin, a yellow spice commonly used in India and several Asian countries, is reported to have anti-tumor and anti-inflammatory effects because of its antioxidant properties. In the present study, we have explored the interaction of curcumin with α₂M using various technique such as antiproteinase activity assay, spectroscopy. Changes in the secondary structure of α₂M following interaction with curcumin was investigated by CD and FT-IR spectroscopy. Thermodynamics of curcumin-α₂M binding were also analyzed by isothermal titration calorimetry to identify the number of binding sites, changes in enthalpy, entropy and Gibbs free energy changes for this interaction. Thermodynamics parameters reveal …