Explore the mechanism of mulberry leaf combined with gut microbiota to improve hyperlipidemia based on network pharmacology

To elucidate the underlying mechanisms by which mulberry leaves, in conjunction with gut microbiota, ameliorate hyperlipidemia and identify key gut microbial taxa involved, a mulberry leaf/gut microbiota-active components-metabolites-target-pathway network was constructed. Information on active constituents of mulberry leaves, metabolites generated by gut microbiota, and target proteins associated with hyperlipidemia were retrieved from multiple databases. Employing bioinformatics tools, relevant pathways and targets involved in the synergistic effect of mulberry leaves and gut microbiota on hyperlipidemia improvement were systematically analyzed. Through multi-level data analysis and integration of existing knowledge on the interplay between mulberry leaves, gut microbiota, and hyperlipidemia, the atherosclerosis signaling pathway was identified as the central pathway, with AKT1 as the core target protein. Based on metabolites produced by gut microbiota that act on AKT1, 29 specific gut microbial strains were found to exhibit synergistic action within the context of mulberry leaf-mediated hyperlipidemia alleviation. This culminated in the establishment of a comprehensive mulberry leaf/gut microbiota-active components-metabolites-target-pathway network. Moreover, molecular docking and visualization analyses demonstrated stable interactions between the selected gut microbiota-derived metabolites and the central target AKT1. These findings provide a robust scientific basis for the application of mulberry leaf-based formulations combined with probiotics in the development of specialized medical foods targeting hyperlipidemia, grounded in the elucidated molecular mechanisms and identified key gut microbial players.