Bioavailability and Activity of Natural Food Additive Triterpenoids as Influenced by Protein

Abstract

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.

Interaction between the anti-cancer drug diacetyl maslinic acid and bovine serum albumin: A biophysical study

“…Little alteration in the fluorescence lifetime of BSA was detected upon the addition of DMA. Similar findings have been reported in literature for several drugs associated with BSA [16,37].…”

“…Despite the ample literature, however, little firm knowledge is available on the binding between albumin and triterpenoids [14][15][16][17], especially on structure-affinity relationship of these compounds with albumin. Clearly, an understanding of the interaction of these pharmaceuticals with albumin is needed to gain insight into their therapeutic effectiveness.…”

A Synthetic Approach for the Rapid Preparation of BODIPY Conjugates and their use in Imaging of Cellular Drug Uptake and Distribution

“…The quantum yields of fluorescence of the conjugates are lower than those of BODIPY‐FL propanoic acid ( Φ =98 for 19 vs. Φ =0.14–0.30 for compounds 24 – 32 ). The diminished fluorescence is probably caused by the static quenching between BODIPY dye and triterpenes, which is consistent with recently published data …”

Energetics of albumin-disuccinylmaslinic acid binding determined by fluorescence spectroscopy

“…Although they were long considered biologically ineffective, recent evidence points to the beneficial effects both of naturally occurring triterpenoids as well as of synthetic derivatives against several types of human diseases, including certain cancers [7][8][9][10]. Naturally occurring triterpenoids such as oleanolic, betulinic, ursolic and maslinic acids have shown significant pharmacological activity, and recent studies suggest a promising potential of these products as anticancer agents [8][9][10][11][12]. Also, several studies examine their interaction with serum albumins [9,[13][14][15][16][17][18][19].…”

“…Naturally occurring triterpenoids such as oleanolic, betulinic, ursolic and maslinic acids have shown significant pharmacological activity, and recent studies suggest a promising potential of these products as anticancer agents [8][9][10][11][12]. Also, several studies examine their interaction with serum albumins [9,[13][14][15][16][17][18][19]. Moreover, it has recently been observed that small structural modifications in these natural substances can produce advantageous derivatives with favorable chemotherapeutic properties [12,16,20].…”