Unveiling the Mechanism Underlying Diyu Shengbai Tablet in Remediating Leukopenia Based on Network Pharmacology, Metabonomics, and Fecal Transcriptomics.

Abstract

We aimed to integrate network pharmacology, metabonomics, and fecal transcriptomics to elucidate the mechanism of action of Diyu Shengbai Tablets (DST) in leukopenia treatment. Key bioactive components and core targets of DST in leukopenia were identified using network pharmacology. Spleen metabonomics, fecal transcriptomics, and MetOrigin analysis were employed to investigate potential mechanisms. Molecular docking, molecular dynamics simulations, and enzyme-linked immunosorbent assay were performed to validate findings. Network pharmacology predicted Hypericin and Quercetin-3-galactoside-7-glucoside as major active constituents of DST. metabonomic analysis identified alterations in 133 differential metabolites in the spleen, with linoleic acid metabolism as the primary affected pathway. 16S rRNA sequencing indicated normalization of Lactobacillus abundance. Molecular docking and dynamics simulations showed low binding free energies between active compounds (e.g., Hypericin) and targets such as PIK3CA and SRC. Serum levels of Mouse interleukin-6 and Granulocyte colony-stimulating factor were elevated following DST intervention. DST modulates spleen metabolic profiles in leukopenic mice, restores gut microbial composition, and exerts therapeutic effects by regulating linoleic acid metabolism and influencing the PI3K-Akt signaling pathway. These findings provide a foundation for further exploration of multi-target mechanisms in traditional Chinese medicine for leukopenia management.