Objective: To investigate the mechanism of Gandou Fumu Decoction in the treatment of hepatolenticular degeneration (HLD, also known as Wilson’s disease) using network pharmacology and molecular docking techniques.

Methods: The chemical constituents of Gandou Fumu Decoction and their corresponding targets were retrieved and screened using databases including TCMSP and UniProt. The intersection between the drug-related targets and disease targets was identified using R (v4.4.0) to determine the potential targets through which Gandou Fumu Decoction may exert therapeutic effects on Wilson’s disease, and the VennDiagram package was employed to visualize the overlapping targets via a Venn diagram. All node information from the network was imported into Cytoscape (v3.9.1) to construct a “traditional Chinese medicine-compound-target-disease” network. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the “clusterProfiler” and “org. Hs. eg. db” packages. Molecular docking simulations were then conducted between the core compounds and key targets to provide preliminary verification of the network pharmacology findings.

Results: Gandou Fumu Decoction may exert its therapeutic effects on Wilson’s disesase through active constituents such as quercetin, β -sitosterol, kaempferol, stigmasterol, and naringin, acting on key targets including B-cell lymphoma 2 (BCL2), RELA proto-oncogene NF- κB subunit (RELA), protein kinase C alpha (PRKCA), and prostaglandin-endoperoxide synthase 2 (PTGS2). The major enriched pathways include lipid metabolism and atherosclerosis, the tumor necrosis factor (TNF) signaling pathway, the PI3K-Akt signaling pathway, hepatitis B, hepatitis C, the interleukin (IL) -17 signaling pathway, the hypoxiainducible factor (HIF)-1 signaling pathway, alcoholic fatty liver disease, and hepatocellular carcinoma. Molecular docking analysis indicates strong binding affinities between the key components and their corresponding targets.

Conclusion: The therapeutic mechanism of Gandou Fumu Decoction in treating Wilson’s disease is characterized by multiple active components, multiple targets, and multiple pathways.