Smilax glabra Roxb. Alleviates Gout through Targeting FOS and CD40LG: Insights from Multi-Omics Integration

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Background Smilax glabra Roxb. (SGB) is traditionally used for gout treatment, but the underlying mechanisms remain unclear. We aimed to explore the effect of SGB on Gout. Methods Active compounds of SGB (oral bioavailability ≥ 30% and drug-likeness ≥ 0.18) were screened from the TCMSP database using network pharmacology, and their potential targets were predicted. Functional enrichment of the identified targets was performed with the clusterProfiler package. For transcriptomic validation, the bulk RNA-seq (GSE160170) and scRNA-seq (GSE211783) datasets from gout patients were used to identify differentially expressed genes. Immune infiltration was assessed by CIBERSORT, and pathway enrichment in classical monocytes was analyzed by gene set enrichment analysis (GSEA). Molecular docking was performed to verify compound-target interactions. Results Network pharmacology identified 13 bioactive compounds and 188 potential targets. Functional enrichment revealed that these targets were involved in inflammatory and immune pathways such as TNF, IL-17, and AGE-RAGE signaling. Intersecting the predicted targets with DEGs from gout patients identified FOS and CD40LG as key overlapping genes associated with gout pathogenesis. Immune infiltration analysis revealed increased monocytes and decreased resting NK cells during acute flares. FOS was positively correlated with monocyte abundance and CD40LG was correlated with resting NK cells. Molecular docking demonstrated stable binding between quercetin and CD40LG (binding energy: -6.58 kcal/mol). These findings were obtained based solely on computational predictions and require further experimental and clinical validation. Conclusion SGB may alleviate gout by regulating inflammatory signaling and immune cell infiltration, particularly monocyte activation, providing mechanistic insights into its anti-gout effect.