Potential Molecular Mechanism of Rubi Fructus in the Treatment of T2DM Based on Multidimensional Biological Network

Objective: To explore the potential targets and underlying mechanism of Rubi Fructus in the treatment of type 2 diabetes mellitus. Methods: Potential active components of Rubi Fructus were proposed by literature search and as well followed the Lipinski’s Rule of Five . The therapeutic targets of potential active components and T2DM-related genes were selected through Swiss target prediction and Gene Cards. The network of potential active components and T2DM-related targets were constructed by Cytoscape 3.7.2, and STRING analysis was performed to reveal the interaction among target proteins and to build the network of protein-protein interaction. Both Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of core targets were performed using David database. Results: Totally, 68 potential active components of Rubi Fructus and 196 T2DM-related targets were found. Among them, 39 key targets were obtained by network analysis, which were primarily enriched on PI3K-Akt, HIF-1, TNF, Toll-like receptor, and Focal adhesion signaling pathways. Conclusion: For the treatment of T2DM, the active compounts of Rubi Fructus can regulate the expression of proinflammatory and oxidative stress mediators and improving insulin resistance through multiple components, targets, and pathways, which offers a scientific support to further Rubi Fructus studies and to the research on T2DM treatment.