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

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.

Pyruvic acid stress caused color attenuation by interfering with anthocyanins metabolism during alcoholic fermentation.

Anthocyanin accounts for wine color performance, while it is susceptive to saccharomyces cerevisiae, causing threatened stability. Considering pyranoanthocyanin performed better color and stability, converting anthocyanins to pyranoanthocyanins in advance during fermentation was an ideal way for color improvement. Thus, pyruvic acid (PA) as the precursor of vitisin A was applied to fermentation with cyanidin-3-O-glucoside (C3G). Results showed that PA-stress leads to a color loss associated with a decrease in C3G and cyanidin. However, the content of pyranoanthocyanins under PA stress is unvaried. LC-MS-based non-target metabolomics revealed that superfluous PA can disturb the process of glycolysis and tricarboxylic acid cycle. Importantly, 1291 molecular features were increased and 1122 were decreased under PA-stress, in which several anthocyanins derivatization and isomerization were changed, contributing to color performance. This study indicated that extra PA is unfriendly to anthocyanins during fermentation, playing an adverse effect on color, which should be avoided in wine production.