Development of dietary supplements to eliminate the atherogenicity of low-density lipoprotein

Abstract

This review systematizes current data on the role of desialylation of lowdensity lipoproteins (LDL) as a key initiating mechanism of atherogenesis that precedes oxidative modification. The structural and functional significance of sialic acid in apolipoproteinB100 is considered, and the enzymes of the sialidase (neuraminidase) family responsible for its cleavage are characterized. The pathogenic role of increased sialidase activity in atherosclerosis, type 2 diabetes mellitus, and other diseases is discussed. Since desialylation occurs at an early stage of LDL modification, preserving the native sialylation pattern may prevent subsequent lipoprotein retention, macrophage uptake, and foam cell formation. This approach has the potential to complement conventional lipid lowering therapy by targeting residual cardiovascular risk through mechanisms independent of plasma LDL cholesterol reduction. The advantages of using dietary supplements based on natural sialidase inhibitors for long-term prevention compared with synthetic drugs are shown. Examples of already existing dietary supplements with antiatherosclerotic effects are described. A separate section is devoted to computer-based approaches, including molecular docking, for the identification of potential sialidase inhibitors among flavonoids. Previously published virtual screening data are discussed, with particular attention to gallated catechins as potential candidates for further experimental investigation. The feasibility of further experimental and clinical studies to create effective and safe nutraceuticals that affect the early stages of atherogenesis is substantiated.
Keywords: Atherosclerosis, lowdensity lipoproteins, sialic acid, desialylation, sialidase, flavonoids, dietary supplements, molecular docking