The mechanism of Gei Herba against type 2 diabetes mellitus: an integration of gut microbiota and network pharmacology analysis

The present study aimed to dissect the underlying mechanism of the Gei Herba (LBZ) in the treatment of type 2 diabetes mellitus (T2DM) based on the gut microbiota and network pharmacology strategies. Thirty-one compounds from LBZ were screened and 187 corresponding targets were identified through the database and literature screening. Multiple disease-associated gene and target databases were used to screen and obtain 726 T2DM-related targets. The gutMGene v1.0 database was used for searching metabolites and targets of gut microbiota. 168 overlapping targets of LBZ, T2DM and the gut microbiota were matched and used to build a protein-protein interaction network and perform enrichment analysis. By bioinformatics analysis of microbiota-pathway-target-compound network, the PI3K-Akt signalling pathway was identified, and potential gut probiotics, such as Eubacterium limosum and Lactobacillus paracasei, were found. Subsequently, the core active compounds in LBZ bind to the core targets were verified by molecular docking, all of which exhibited good binding affinity. Finally, four compounds, eleutheroside A, gallic acid, kaempferol, and protocatechuic acid, were found to conform to Lipinski’s rule and be non-toxic, showing great potential in the treatment of T2DM. These findings suggest the potential mechanism of LBZ in the treatment of T2DM and the core compounds, such as eleutheroside A may be the promising candidates for T2DM treatment.