Exploring the Mechanism of Baicalein in Treating Oral Lichen Planus: A Network Pharmacology and Single-cell RNA Sequencing Analysis

Background Oral lichen planus (OLP) is a prevalent chronic inflammatory oral mucosal disease with an uncertain pathogenesis and limited treatment options. Purpose: This study aimed to systematically explore the underlying therapeutic mechanisms of baicalein in the treatment of OLP using network pharmacology and single-cell RNA sequencing analysis. Materials and Methods Baicalein target genes were sourced from the Comparative Toxicogenomics Database, SwissTargetPrediction, PharmMapper Server, and TargetNet. OLP gene expression data were retrieved from the GSE52130 dataset. Differentially expressed genes (DEGs), gene set enrichment analysis, and weighted gene co-expression network analysis (WGCNA) were performed to identify OLP-related targets by comparing DEGs with significant WGCNA modules. PPI networks were constructed using STRING and Cytoscape, and MCODE subgroup genes were assessed via t -tests and receiver operating characteristic (ROC) analysis. Immune infiltration analysis explored the immunomodulatory mechanisms. Single-cell RNA-seq identified cell types in erosive oral lichen planus (EOLP) and non-erosive oral lichen planus (NEOLP) groups and potential baicalein-sensitive cells. Molecular docking validated the target interactions. Results We identified 192 candidate targets of baicalein and 502 DEGs in OLP, with 409 OLP-related target genes emerging from the intersection of DEGs and WGCNA’s pink and paleturquoise modules. PPI network and MCODE analysis refined these to 48 essential subgroup genes, which were further analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, ultimately revealing 30 hub genes validated by t -test and ROC analysis. Immune infiltration analysis demonstrated baicalein’s regulatory effects on CD8 + T cells and B cells, mitigating OLP-related immune dysregulation. Single-cell RNA sequencing highlighted divergent cell populations between EOLP and NEOLP groups, with monocytes emerging as key baicalein targets, supported by molecular docking confirming strong interactions with hub genes. Conclusion This study uncovered baicalein’s multi-target mechanism in OLP, spanning immune regulation, metabolic reprogramming, and monocyte modulation, offering a rationale for preclinical validation.