Abstract
Limited evidence suggests that the abundance of antioxidant polyphenols in dry red wine (DRW) may prevent cardiovascular diseases, a benefit likely attributed to abundant antioxidant polyphenols present in DRW. Here, we examined the anti-atherosclerotic effect of Cabernet Sauvignon DRW (CSDRW) in a mouse model of atherosclerosis (AS) using metabolomic profiling and molecular techniques. Oral administration of CSDRW reduced atherosclerotic lesion size in ApoE-/- mice, alleviated hyperlipidemia, ameliorated hepatic lipid accumulation mediated by AMPK activation, and promoted lipid metabolism via PPARγ-LXR-α-ABCA1 pathway regulation. CSDRW increased the relative abundance of beneficial gut microbiota, including Bacteroidetes, Verrucomicrobiota, and Akkermansiaceae. Metabolic analysis using liquid chromatography-tandem mass spectrometry revealed that CSDRW contained various polyphenols, including flavanol, phenolic acid, flavonol, and resveratrol, which possibly mediate the beneficial effects in AS by reducing inflammation, restoring normal endothelial function, regulating hepatic lipid metabolism, and modulating gut microbiota composition.