Lupin LILPKHSDAD (P5) peptide is a novel bi-functional inhibitor of PCSK9, a new target for the hypercholesterolemia treatment

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new target for hypercholesterolemia treatment.[1] Interestingly, we have observed that in mild hypercholesterolemic subjects, which had consumed lupin protein (30 g/day) for 4 weeks, the final circulating PCSK9 level had been reduced by 8.5% versus baseline value. In addition, we have also provided evidences related to the mechanism of action by which lupin peptides may modulate PCSK9 in HepG2 cells.[2] In this context, we have demonstrated that LILPKHSDAD (P5), a peptide deriving from peptic lupin protein hydrolysis and absorbable at intestinal level, is able to modulate the PCSK9 target with a dual mechanism of action. In particular, P5 peptide reduces PCSK9 production and secretion through a decrease of HNF1-alpha in HepG2 cells and an absorbed lupin peptide is able to inhibit the protein-protein interaction between PCSK9 and the LDL receptor with an IC50 value equal to 1.6\ub10.33 \u3bcM. All these evidences contribute to explain the beneficial hypocholesterolemic effects of lupin peptide, which were observed in clinical studies and opening a new area of investigation on plant proteins