Soy peptides with hypocholesterolemic activity: absorption and metabolism study across Caco-2 cell monolayers

Plant proteins are useful in the prevention of cardiovascular disease and diabetes. In particular, some studies have demonstrated that soybean proteins, among the main bioactive components of this bean, are able to reduce total and low-density lipoprotein (LDL) cholesterol levels in highly and mildly hypercholesterolemic subjects [1,2], through a positive effect on LDL receptors (LDLR). Furthermore, recently, it has been proved that IAVPGEVA, IAVPTGVA, and LPYP, three peptides deriving from glycinin, a main fraction of soy globulins, induce a hypocholesterolemic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl CoA reductase, thus modulating the cholesterol metabolism in HepG2 cells [3]. In addition, recent observations have suggested that the same peptides exert hypoglycemic activity modulating the glucose metabolism at the HepG2 cells through the activation of Akt and AMPK pathway [4]. All of them are also able to interfere with dipeptidyl peptidase IV (DPP-IV), a new molecular target correlated with the development of type 2 diabetes [5]. On this basis, the scarce information about their ability to be absorbed at intestinal level led us to elucidate their absorption and metabolic degradation across Caco-2 cells. In details, quantitative based-mass spectrometric assays, such as LC-MRM, were developed in order to obtain quantitative information about the degree of absorption of IAVPGEVA, IAVPTGVA, and LPYP across Caco-2 cells, as well as to get a structural characterization of their metabolites generated during incubation. Quantitative data revealed that soy peptides are absorbed by the intestinal epithelium and are extensively metabolized by brush border peptidases including DPP-IV, for which they are good inhibitors and substrates, as supported by molecular modeling.