A multidisciplinary investigation on the bioavailability and activity of peptides from lupin protein

There is currently a growing interest for discovering bioactive peptides encrypted in food proteins. Numerous investigations have shown that the lupin protein consumption provides useful health benefits, especially in the area of cholesterol reduction.1 Recently, we have demonstrated that tryptic and peptic peptides from lupin protein modulate cholesterol metabolism in human hepatocytes (HepG2 cells) and increase LDL-uptake, with a statin-like mechanism.2 In order to evaluate the bioavailability and bioactivity of these peptides, an in vitro trans-epithelial transport study across differentiated human intestinal enterocytes (Caco-2 cells) was performed. HPLC-Chip-MS/MS permitted the identification of eleven tryptic and eight peptic peptides transferred to the basolateral compartment (BL).3 An in vitro assay showed that BL peptides maintain their capacity to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) activity and in silico docking simulations permitted to hypothesize which peptides may bind more efficiently to the HMGCoAR catalytic site. Furthermore, a co-culture system, in which Caco-2 cells and HepG2 cells were combined, permitted to confirm the hypocholesterolemic activity of BL lupin peptides on HepG2 cells. The experiments showed that BL peptides not only maintained their bioactivity on HepG2 cells, but that this activity was improved by the crosstalk of the two cells systems in co-culture. In addition, lupin peptides showed a positive influence on cholesterol metabolism in Caco-2 cells and decreased the proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion. This is the first investigation providing evidence that specific lupin peptides are potentially absorbed in enterocytes. These findings may help explaining the beneficial effects observed in experimental models and in human studies.