Peptide from α’ chain of 7S soy globulin lowers plasma lipids through SREBP-2 and PCSK9 pathways in cholesterol-fed rats

Aim of the study was to evaluate the effect of NPDNDE, a synthetic peptide (position 314-319) of α’ chain 7S soy globulin, on cholesterol homeostasis both in HepG2 cells and in casein-cholesterol (HC diet) fed rats. In vitro experiment: Hep G2 cells were incubated (24 h) in MEM + 5% LPDS w/wo whole α’ subunit (3.5 μM), or synthetic peptide (0.1 µM), or simvastatin (1 μM). At the end of incubation, cells were processed for SREBP2, LDL-R and PCSK9 mRNAs by RT-PCR. Increased mRNA expression of SREBP2 (+1.5; 1.2 fold), LDL-R (+2.5; 2.5 fold) and PCSK9 (+3.5; +1.5 fold) were detected in cells exposed to NPDNDE and simvastatin, respectively vs control cells. In vivo experiment: HC diet fed rats were daily treated by gavage with synthetic peptide NPDNDE (5 mg/Kg b.w.) for 21 days; the results were compared with that obtained in rats treated either with whole α’ (20 mg/Kg b.w.) or clofibrate (200 mg/kg b.w.), as reference drug. The oral administration of peptide resulted in lower plasma lipid levels (C, cholesterol, -25%; TG, triglycerides, -28%) vs values recorded in rats fed casein-cholesterol diet alone. Four-fold amounts of α’ chain reduced C and TG by 27 and 32%, respectively. Similar results were obtained in clofibrate-treated rats. Moreover, synthetic peptide increased expression of mRNA LDL-R (+ 53%), thus restoring receptor activity suppressed by HC diet. This is the first in vivo evidence of potential activity of the NPDNDE synthetic peptide from α’chain 7S soy globulin on lipid homeostasis through SREBP-2 and PCSK9 pathways.