Cholesterol-Lowering Activity of Vitisin A Is Mediated by Inhibiting Cholesterol Biosynthesis and Enhancing LDL Uptake in HepG2 Cells

Abstract

Pyranoanthocyanins have been reported to possess better chemical stability and bioactivities than monomeric anthocyanins in some aspects. The hypocholesterolemic activity of pyranoanthocyanins is unclear. In view of this, this study was conducted to compare the cholesterol-lowering activities of Vitisin A with the anthocyanin counterpart Cyanidin-3-O-glucoside(C3G) in HepG2 cells and to investigate the interaction of Vitisin A with the expression of genes and proteins associated with cholesterol metabolism. HepG2 cells were incubated with 40 μM cholesterol and 4 μM 25-hydroxycholeterol with various concentrations of Vitisin A or C3G for 24 h. It was found that Vitisin A decreased the cholesterol levels at the concentrations of 100 μM and 200 μM with a dose–response relationship, while C3G exhibited no significant effect on cellular cholesterol. Furthermore, Vitisin A could down-regulate 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) to inhibit cholesterol biosynthesis through a sterol regulatory element-binding protein 2 (SREBP2)-dependent mechanism, and up-regulate low-density lipoprotein receptor (LDLR) and blunt the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein to promote intracellular LDL uptake without LDLR degradation. In conclusion, Vitisin A demonstrated hypocholesterolemic activity, by inhibiting cholesterol biosynthesis and enhancing LDL uptake in HepG2 cells.

Lactobacillus plantarum J26 postbiotics alleviate high‐fat and high‐cholesterol diet‐induced hypercholesterolemia via regulating the LXRα‐CYP7A1‐bile acid‐excretion pathway

“…The J26P intervention increased the relative expression of LDLR in the liver compared with HCD controls, suggesting that J26P may reduce serum and liver LDL‐C levels by increasing LDLR expression. It was shown that Pyranoanthocyanins can promote intracellular LDL uptake by upregulating the expression level of LDLR in HepG2 cells, showing hypocholesterolemia activity, which is consistent with the results of the present study (Yuan et al., 2023). SREBP‐2 regulates the expression of HMGCR, the rate‐limiting enzyme in cholesterol synthesis, and LDLR‐mediated cholesterol absorption (Y. Li et al., 2017).…”

“…Accordingly, we further explored the effect of J26P on the expression of key proteins of liver cholesterol metabolism. HMGCR is the rate‐limiting enzyme for the de novo synthesis of cholesterol in vivo (Yuan et al., 2023). In addition, J26P does not affect the expression of liver HMGCR in mice.…”

“…In addition, J26P does not affect the expression of liver HMGCR in mice. LDLR plays an important role in maintaining normal blood cholesterol levels in the body by taking up cholesterol from LDL‐C in the serum into the cells for steroid hormones, cell proliferation, and bile salt synthesis (Yuan et al., 2023). The J26P intervention increased the relative expression of LDLR in the liver compared with HCD controls, suggesting that J26P may reduce serum and liver LDL‐C levels by increasing LDLR expression.…”

Regulation of cholesterol metabolism: New players for an old physiological process

“…[97][98][99][100] Several studies have highlighted the role of long-chain polyunsaturated fatty acids in regulating the levels and/or expression of proteins involved in cholesterol synthesis, uptake, and transport in peripheral tissues as well as in the brain. [101][102][103][104][105][106] Preclinical studies have also noted that many flavonoids (e.g., anthocyanidins, flavanols, and flavone subclasses) influence cholesterol metabolism by regulating cellular cholesterol synthesis, 107,108 efflux, 109,110 and by inhibiting intestinal absorption. 111,112 Furthermore, in clinical studies dietary intake of flavonoids has been associated with beneficial changes in serum biomarkers related to cholesterol metabolism.…”

The promising stability of carboxylpyranocyanidin‐3‐O‐glucoside during food processing and simulated digestion and its bioavailability research

“…In our previous study, carboxylpyranocyanidin-3-O-glucoside (carboxyl-pycy-3-gluc) was successfully generated by employing the black soybean peel extracts and pyruvic acids through a 15-day reaction in a water bath. 12 The high purity of carboxyl-pycy-3-gluc was then achieved using preparative medium-pressure liquid chromatography, for which the purity is over 96%. We also demonstrated that carboxyl-pycy-3-gluc demonstrated an absence of cytotoxicity and a more effective hypocholesterolemia activity compared to Cy-3-gluc, as well as an excellent immunomodulatory effect.…”