Exploring the Potential Role and Mechanism of Quercetin in the Treatment of Primary Sjögren's Syndrome Based on Network Pharmacology, Molecular Docking, and Experimental Validation

Objective This study investigates Quercetin’s effects on lymphocyte infiltration and salivary function in primary Sjögren’s Syndrome (pSS) mice and explores its mechanisms via network pharmacology, molecular docking, and experimental validation. Methods pSS model mice and controls were divided into four groups (control, model, Quercetin, hydroxychloroquine). After 12 weeks, saliva flow and submandibular gland histopathology were assessed. Network pharmacology identified Quercetin’s targets, followed by GO/KEGG analyses. Molecular docking and qPCR validated core targets. Results Quercetin reduced lymphocyte infiltration, improved saliva flow, and targeted 138 genes (TP53, TNF, JUN, AKT1, IL6 as core). GO/KEGG linked targets to lipopolysaccharide response, oxidative stress, TNF, and atherosclerosis pathways. Quercetin showed strong binding to core targets and downregulated Tp53/Jun mRNA. Conclusion Quercetin alleviates salivary gland damage in pSS by modulating inflammation/immunity pathways, highlighting its therapeutic potential. This study supports further exploration of Quercetin for pSS treatment.