Bioavailability and activity of natural food additive triterpenoids as influenced by protein

Triterpenoids were thought to be biologically ineffective for a very long time, but aggregating proof on their widely ranging pharmacological activities paired with a dubious toxicity portrait has motivated regenerated attraction for human health and disease. In the current contribution, our central goal was to integratively dissect the biointeraction of two typical triterpenoids, ursolic acid and oleanolic acid, by the most fundamental macromolecule bovine serum albumin (BSA) by employing molecular modeling, steady state and time-resolved fluorescence, and circular dichroism spectra at the molecular scale. Based on molecular modeling, subdomain IIA, which matches Sudlow's site I, was allocated to retain high affinity for triterpenoids, but the affinity of ursolic acid with subdomain IIA is somewhat inferior compared to that of oleanolic acid, probably because the affinity differentiation arises from the different positions of the methyl group on the E-ring in the two triterpenoids. This sustains the site-specific ligands, and hydrophobic 8-anilino-1-naphthalenesulfonic acid probe results in arranging the triterpenoids at the warfarin-azapropazone site. The data of steady state and time-resolved fluorescence indicated that the recognition of triterpenoids by BSA produced quenching by a static type, in other words, the ground state BSA-triterpenoid complex formation with the affinities of 1.507/1.734, 1.042/1.186, and 0.8395/0.9863 × 10(4) M(-1) at 298, 304, and 310 K for ursolic acid/oleanolic acid, respectively. Thermodynamic analyses show that the basic forces acting between BSA and triterpenoids are hydrogen bonds, van der Waals forces, and hydrophobic interactions; this occurrence provoked the alterations of the BSA spatial structure with a noticeable decline of α-helix evoking perturbation of the protein, as stemmed from circular dichroism, synchronous fluorescence, and three-dimensional fluorescence measurements. We anticipate that the complexation of plant triterpenoids with protein delineated here may be exploited as a biologically relevant model for evaluating the physiologically applicable noncovalent complexes in in vivo examination of triterpenoid properties such as accumulation, bioavailability, and distribution.