Differences in the molecular structure of curcumin and its breakdown products affect their inhibitory effect on pepsin: Kinetic and protein spatial conformation study

Curcumin, a natural phenolic compound with various bioactivities, is easily decomposed into stability ferulic acid and vanillin molecules. Whether the functional equivalence of decomposition products can match that of curcumin is a matter worth attention. In this work, the inhibition and interaction of curcumin and its decomposition products on pepsin were studied. The inhibition by curcumin and ferulic acid belonged to competitive inhibition, the quenching types were static quenching with spontaneous process. Binding energies of curcumin, ferulic acid and vanillin were −8.33 ± 0.14, −7.88 ± 0.09 and −6.12 ± 0.08 kcal/mol, respectively, through H-bonds and hydrophobic interactions. All molecules significantly changed the secondary structure of pepsin and reduced the deformation temperature about 15 °C. The results show that better inhibition on pepsin from curcumin than ferulic acid, whereas vanillin did not show inhibition. The results provided the experimental basis for curcumin as potential inhibitors of pepsin in special diets. • Curcumin shows the best inhibitory effect on pepsin than its decomposition products. • Inhibition of pepsin by curcumin and ferulic acid is based on competitive inhibition. • Curcumin improves stability and inhibition through more binding sites. • Vanillin does not exhibit pepsin inhibition due to the absence of a "-CH 2 COOH" structure.