The synergistic lipogenesis inhibition and molecular mechanism of polyphenols and polysaccharides from mulberry leaf

The present study investigated the lipogenesis inhibition effect of mulberry leaf polyphenols (MLPP), polysaccharides (MLPS), polyphenols-polysaccharides complex (PPPS, with a total content portion of 1:2), and the mechanism of polyphenols and polysaccharides synergistic interaction. fatty liver human hepatocellular carcinomas (HepG2) and human colorectal adenocarcinoma (Caco-2)/HepG2 cells co-culture model were established to evaluate the lipogenesis inhibition, while real-time quantitative PCR (RT-qPCR) and non-targeted metabolomics were applied for molecular mechanism elucidation. The results demonstrated that the lipid droplet and total glyceride (TG) inhibition effect of PPPS after in vitro digestion and colon fermentation was better than that of MLPP and MLPS groups, indicating synergistic interaction of polyphenols and polysaccharides. Besides, The PPPS achieved synergism regulation on lipid metabolism through 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR)/Acetyl CoA carboxylas (ACC) signaling pathways. In addition, glycerophospholipids, gamma-aminobutyric acid-betaxanthin and luteolin were the key differential metabolites for synergistic lipogenesis in PPPS group. Furthermore, the differential signaling pathways mainly involved mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB), which might be potential targets for the synergistic interaction as verified by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.