Cholesterol-lowering effects of phytosterol combined with phosphatidylcholine and their mechanism of action in hypercholesterolemic rats

The potential efficacy and underlying mechanisms of phosphatidylcholine (PC) combined with phytosterol (PS) for regulating hypercholesterolemia in rats fed a high cholesterol diet (HCD) were investigated. After 10 weeks of PS and/or PC intervention, compared with the HCD group, the serum total cholesterol and low-density lipoprotein cholesterol levels in low-, medium-, and high-dose PC and PS (LPC-PS, PC-PS, and HPC-PS, respectively) groups were significantly decreased. PC combined with PS can significantly reduce the liver cholesterol level, improve abnormal liver function, and lower the inflammatory level in rats with hypercholesterolemia. The combined intervention can improve the fluidity of the erythrocyte membrane and reduce serum and liver cholesterol levels by affecting erythrocyte composition and liver lipids in hypercholesterolemia rats. As per the lipidomics of erythrocytes, PC combined with PS can regulate the pathway closely related to hypercholesterolemia, such as sphingolipid, glycerophospholipid, and cholesterol metabolism. Lipidomic pathway analysis in liver tissues suggested that the protective effect of PC and PS may be related to the regulation of fat digestion and absorption, cholesterol metabolism, steroid biosynthesis and glycerophospholipid metabolism. In addition, the combined intervention of PC and PS could increase the expression of LDLR, LXRα, CYP7A1, ABCG5/8 genes and inhibit the expression of ACAT2, SREBP2, and HMGCR genes and thus improve lipid metabolism disorder in hypercholesterolemia rats. The combined use of PC and PS is a safe and effective strategy for preventing hypercholesterolemia.