Two Peptides from Soy β-Conglycinin Induce a Hypocholesterolemic Effect in HepG2 Cells by a Statin-Like Mechanism: Comparative in Vitro and in Silico Modeling Studies

Two peptides from soybean beta-conglycinin, i.e., YVVNPDNDEN (peptide 2) and YVVNPDNNEN (peptide 3), are known to be absorbed by human enterocytes. The former is a fragment of LRVPAGTTFYVVNPDNDENLRMIA (peptide 1), previously shown to increase the low-density lipoprotein (LDL) uptake and degradation in hepatocytes. Research carried out in silico on their interactions with the catalytic site of 3-hydroxy-3-methylglutaryl CoA reductase. (HMGCoAR) demonstrated that they behave as competitive inhibitors of HMGCoAR activity with a statin-like mechanism, confirmed by direct inhibition experiments. Research in HepG2 cells aimed at investigating the effects of these peptides on cholesterol metabolism showed that compared to mock treatment peptide 2 at 350 mu M up-regulates the mature SREBP2 protein level by 134.0 +/- 10.5%, increases the LDLR protein level by 152.0 +/- 20.0%, and enhances the HMGCoAR protein production by 171 +/- 29.9%, whereas peptide 3 upregulates the mature SREBP2 protein level by 158.0 +/- 9.2%, increases the LDL level 164.0 +/- 17.9%, and induces a HMGCoAR protein increase by 170 +/- 50.0%.