Insights into the potential mechanism of Beiqishen Jiangtang Granule in the treatment of type 2 diabetes nephropathy: A study based on network pharmacology, molecular docking, and biological validation

Beiqishen Jiangtang Granule, derived from Huangqi Liu Yi Tang and Shengmai Yin, plays a significant role for the therapy of type 2 diabetes mellitus (T2DM). However, the underlying molecular therapeutic mechanisms remain unclear. This study uses an integrated approach combining network pharmacology, molecular docking, and in vitro validation experiments to explore potential bioactive compounds, key targets, major signaling pathways, and underlying molecular mechanisms of Beiqishen Jiangtang Granule in the treatment of T2DM. In this study, network analysis was employed to screen metabolites and potential targets using the TCMSP database, followed by Gene Ontology, kyoto encyclopedia of genes and genomes enrichment analyses to predict the underlying mechanisms, and the protein encoded by the core target was docked with the active ingredient. Using a streptozotocin-induced approach, a T2DM rat model was established to evaluate the bioactivity of Beiqishen Jiangtang Granule on blood glucose levels, lipid profiles, inflammatory cytokines, gene expression, and gut microbiota composition. Network analysis identified 121 primary metabolites and 30 key targets in Beiqishen Jiangtang Granule. Integrated Gene Ontology and kyoto encyclopedia of genes and genomes analyses (27 items) predicted that Beiqishen Jiangtang Granule regulates serum contents of insulin, tumor necrosis factor-alpha, and interleukin-6, and modulates TP53, Akt, and PI3K protein expression to exert hypoglycemic effects. Animal studies confirmed Beiqishen Jiangtang Granule significant glucose-lowering action via these pathways and mRNA regulation. Additionally, Beiqishen Jiangtang Granule was shown to rebalance gut microbiota by enriching beneficial bacterial communities and suppressing the growth of harmful bacteria, aiding T2DM treatment. These findings demonstrate Beiqishen Jiangtang Granule's characterized by multiple components, targets, and pathways mechanisms in treating T2DM. Beiqishen Jiangtang Granule have a very significant therapeutic effect on T2DM by regulating the concentrations of insulin, tumor necrosis factor-alpha and interleukin-6 in serum and influencing the expressions of TP53, Akt and PI3K proteins and mRNA. In addition, Beiqishen Jiangtang Granule can also regulate the imbalance of intestinal flora related to T2DM in patients by promoting the proliferation of beneficial bacteria and inhibiting harmful bacteria, thereby assisting T2DM.