Assessing the bioavailability of bioactive peptides from lupin seed protein by using differentiated human intestinal enterocytes

The majority of bioactive food compounds responsible for the positive effects on well-being are predominantly derived from the plant kingdom. Numerous investigations have shown that the consumption of lupin protein provides useful various health benefits, especially in the area of cholesterol reduction,1 as well as high blood pressure modulation,2 and hyperglycaemia prevention.3 Interestingly, tryptic and peptic peptides from lupin proteins modulate cholesterol metabolism in HepG2 cells and increase LDL-uptake, with a statin-like mechanism.4 There is now a great interest to discover bioactive peptides encrypted in food proteins that may be responsible for the observed activities, once they are released by digestion from the parental protein and absorbed at intestinal level. In order to evaluate the bioavailability and bioactivity of tryptic and peptic peptides derived from L. albus seed protein, a novel foodomic approach was developed. It comprises the in vitro trans-epithelial transport study, reproduced across differentiated human intestinal enterocytes (Caco-2 cells), and the identification of absorbed peptides using HPLC-Chip-MS/MS technique. Eleven tryptic and eight peptic peptides, deriving from the main lupin storage proteins, were identified in the basolateral samples of cellular bicameral system. Further, an in vitro assay showed that basolateral peptides maintain their capacity to inhibit 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. This is the first investigation providing evidence that lupin peptides with specific structures are potentially absorbed in human intestinal cells. These findings may help explaining the beneficial effects observed in vivo in animal and human studies.