Network Pharmacology and Bioinformatics Analysis to Reveal the Mechanism of Chinese Herbal Formula in the Treatment of Sjögren’s Syndrome

Introduction: Qi-Ju-Di-Huang-Wan (QJDHW), a traditional herbal remedy frequently utilized, has been used in managing Sjögren’s syndrome (SS) in China. However, the pharmacological mechanism remains unclear. Here, we aimed to investigate the therapeutic mechanisms of QJDHW in the treatment of SS through performing a network pharmacology analysis. Materials and Methods: The bioactive components and corresponding targets of QJDHW were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while SS-related genes were obtained from the DisGeNET and GeneCards platforms. Overlapping targets between QJDHW and SS were used to construct a Protein-Protein Interaction (PPI) network with the help of Cytoscape and the BisoGenet plugin. To further elucidate the underlying mechanisms, functional enrichment was conducted using Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, molecular docking was performed to evaluate the binding affinity between selected active ingredients and target proteins. Results: QJDHW comprises eight medicinal herbs containing 82 bioactive compounds and 142 predicted targets. Among these, 29 targets overlapped with SS-associated genes and were considered potential therapeutic targets. Protein–Protein Interaction (PPI) network analysis identified 221 core genes. Functional enrichment analysis yielded 2,036 Gene Ontology (GO) terms and 121 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, with significant enrichment (adjusted p < 0.05) in pathways including MAPK signaling, apoptosis, and viral infection–related pathways. Molecular docking revealed strong binding affinities between representative compounds (e.g., luteolin, quercetin) and core targets (e.g., ESR1, NTRK1), with binding energies all ≤ –7.0 kcal/mol, confirming potential molecular interactions underlying QJDHW’s therapeutic effects. Discussion: The therapeutic action of QJDHW may involve modulation of pathways related to immune responses, antiviral defenses, and apoptosis regulation. Notably enriched path-ways included MAPK signaling, apoptosis, and those associated with viral infections such as human T-cell leukemia virus type 1, hepatitis C, and Epstein-Barr virus. Molecular dock-ing supported the interaction between key compounds and selected targets. Conclusion: This network pharmacology study indicates that QJDHW may exert therapeu-tic effects in SS by targeting multiple bioactive compounds, genes, and biological pathways, particularly those involved in antiviral activity, immune modulation, and inhibition of apop-tosis.