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±0.33 μM. 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.