Food-derived peptides with hypocholesterolemic activity: Production, transepithelial transport and cellular mechanisms

In recent years, food-derived peptides have gained much attention for their potential health benefits. Some short and medium-sized peptides released from food proteins after their enzymatic hydrolysis may exhibit hypocholesterolemic activity. Hypocholesterolemic peptides act either by targeting exogenous cholesterol in the gastrointestinal (GI) tract or by modulating endogenous cholesterol levels via cholesterol metabolism pathways in the liver after being absorbed. This paper provides a comprehensive review of current pieces of evidence regarding the production, transepithelial transport, and cellular mechanisms underlying the hypocholesterolemic activities of food-derived peptides. The molecular mechanisms of hypocholesterolemic peptides involve bile acid binding, inhibition of cholesterol micellar solubility, statin-like effects through the modulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCoAR), as well as the targeting of interactions between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR), sterol regulatory element-binding protein 2 (SREBP-2), and hepatocyte nuclear factor 1α (HNF-1α) pathways. Furthermore, some peptides exhibit multiple biological activities, such as anti-inflammatory and antioxidant activities, besides cholesterol-lowering properties, thereby safeguarding cellular components against high levels of cholesterol-induced damage. However, since only a few studies have evaluated the in vivo effects of hypocholesterolemic peptides, further studies carried out in animal models or human are necessary to exploit these ingredients in the prevention and management of hypercholesterolemia. •Some peptides exert their activity through the modulation of HMGCoAR.•Some peptides inhibit the interactions between PCSK9 and LDL receptor.•They may be used in the prevention of hypercholesterolemia.