Flaxseed-derived peptide, IPPF, inhibits intestinal cholesterol absorption in Caco-2 cells and hepatic cholesterol synthesis in HepG2 cells

Flaxseed peptides reduced serum cholesterol levels in Sprague-Dawley rats fed with a high-cholesterol diet. However, the mechanism of this action remains unclear. Flaxseed-hydrolyzed proteins were separated through ultrafiltration. The fifth fraction (FP5, <= 1 kDa) had the highest cholesterol micelle solubility inhibition rate (CMSR) of 72.39% among the other fractions. Eleven peptides were identified from FP5. Ile-Pro-Pro-Phe (IPPF), which had the highest CMSR of 93.47%, was selected for further analyses. IPPF substantially reduced the cholesterol transported content in Caco-2 cells and the total cholesterol content in HepG2 cells. Moreover, IPPF modulated the protein levels of NCP1L1 and ABCG5/8 (cholesterol transporters) in Caco-2 cells and reduced the mRNA levels of Srebp-2 and Hmgcr (cholesterol synthesis enzymes) in HepG2 cells. IPPF inhibits cholesterol intestinal absorption by modulating the cholesterol transporters expression and reduces hepatic cholesterol synthesis by inhibiting the SREBP2-regulated mevalonate pathway. IPPF is a new food-derived cholesterol-lowering nutritional supplement. Practical applications We isolated active peptides with cholesterol-lowering properties from flaxseed protein, a by-product of industrial oil production, which greatly improved the economic and medicinal value of flaxseed protein. According to our research, IPPF can be used as a new food-derived type of cholesterol intestinal absorption inhibitor to reduce dietary cholesterol absorption and cholesterol synthesis inhibitor (same pharmacological mechanism as statins). IPPF provide a nutritional therapy component for hypercholesterolemia and prevent atherosclerosis. Our research provides theoretical basis for development and utilization of new nutritional supplements and plant proteins.

Automated summary

The study isolated IPPF from flaxseed protein, which effectively reduces serum cholesterol levels, modulates cholesterol metabolism, and has potential nutritional therapeutic value.