Behavior of three hypocholesterolemic peptides from soy protein in an intestinal model based on differentiated Caco-2 cell. (June 2018)

• Record Type: Journal Article
• Authors: Aiello, Gilda; Ferruzza, Simonetta; Ranaldi, Giulia; Sambuy, Yula; Arnoldi, Anna; Vistoli, Giulio; Lammi, Carmen
• Is Part Of: Journal of functional foods. Volume 45(2018)
• Page Start: 363
• Page End: 370
• Publication Date: 2018-06
• Subjects: Hypocholesterolemic peptides -- Caco-2 cells -- DPP-IV -- HMGCoAR -- In silico docking -- Intestinal absorption -- LC-MRM -- Mass spectrometry -- Soy protein; ACN acetonitrile -- AP apical -- BL basolateral -- CV coefficient of variance -- DMEM Dulbecco's Modified Eagle Medium -- EDTA ethylenediamine tetraacetic acid -- FBS Fetal Bovine Serum -- H-Gly-Pro-AMC H-Gly-Pro-aminomethylcoumarin -- HMGCoAR 3-hydroxy-3-methylglutaryl coenzyme A reductase -- IS internal standard -- LC liquid chromatography -- LDL low density lipoprotein, LDLR, LDL receptor -- LOD limit of detection -- LOQ limit of quantification -- MRM multiple reaction monitoring -- R2 correlation coefficient -- SD standard deviation -- SREBP-2 sterol regulatory element binding proteins 2 -- TEER trans-epithelial electrical resistance -- tR ritention time; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2018.04.023
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: IAVPGEVA, IAVPTGVA, and LPYP, 3 soy peptides, are absorbed by Caco-2 cells. A specific LC-MRM method was developed for their quantification. The peptides are in part hydrolyzed to fragments by brush border peptidases. IAVPGEVA, IAVPTGVA, and LPY are substrates of DPP-IV. Abstract: IAVPGEVA, IAVPTGVA, and LPYP, three peptides deriving from soy protein hydrolysis, inhibit the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) and modulate cholesterol metabolism in HepG2 cells. In order to assess whether these hypocholesterolemic peptides can be absorbed across the epithelium barrier, experiments were performed using human intestinal Caco-2 cell monolayers grown in two-compartments systems. Each peptide (500 µM) was incubated in the apical compartment for a time spanning from 15 to 120 min and quantified in the basolateral compartment using a highly sensitive LC-MRM method. The peptides were partially absorbed across the Caco-2 monolayers, but they were also hydrolyzed to shorter fragments by brush border peptidases. Possibly dipeptidyl peptidase IV, the main protease expressed on differentiated cells, had not a main role in this metabolism, since these peptides act as competitive inhibitors of this enzyme. In silico docking simulations suggested that some metabolites may retain a hypocholesterolemic activity.