Dual mechanisms of Vitisin A in managing alcoholic liver disease: Inhibition of lipogenesis and complement activation.

Pyranoanthocyanins in aged red wine show superior stability, pigmentation, antioxidative, anti-inflammatory, and hypocholesterolemic properties compared to unmodified anthocyanin precursors in vitro. However, evidence supporting their health benefits in vivo remains limited. This study evaluated the hepatoprotective effects of Vitisin A compared to Cyanidin-3-O-glucoside using Lieber-DeCarli mouse and AML12 cell models. Additionally, mulberry wine anthocyanins and their aged counterparts were evaluated in vivo. All anthocyanin treatments significantly alleviated ethanol-induced hepatic steatosis and improved alcohol metabolism. Notably, Vitisin A markedly reduced plasma AST and ALT levels (p < 0.05), a result not observed with C3G. RNA-seq analysis showed Vitisin A induced significant gene expression changes, especially in complement system and lipid metabolism pathways. It inhibited fatty acid synthesis by upregulating p-AMPK/AMPK and p-ACC/ACC ratios, suppressing FASN expression, and reduced complement activation by downregulating C3 and decreasing C3ar1 and Tnf-α expression, mitigating Kupffer cell-mediated inflammation. In contrast, C3G and ACNS had limited effects on these pathways, particularly in complement modulation. These findings highlight the dual actions of vitisin A in inhibiting de novo lipogenesis and complement activation, demonstrating its superior efficacy over C3G. This study underscores the therapeutic potential of vitisin A as a functional food component for managing alcoholic liver disease.