Integrated InPETM drug analysis and transcriptomics to explore potential mechanisms and key active components of multiple traditional Chinese medicine prescriptions for psoriasis.
BACKGROUND Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by epidermal hyperproliferation, skin barrier dysfunction, and immune dysregulation, with a complex pathogenesis. This study aimed to investigate the potential molecular mechanisms underlying the therapeutic effects of traditional Chinese medicine (TCM) compound prescriptions for psoriasis. METHODS The psoriasis transcriptomic dataset GSE14905 was downloaded from the Gene Expression Omnibus (GEO) database. Psoriasis-related genes and TCM compound prescriptions for psoriasis were collected. Differentially expressed gene (DEG) analysis and functional enrichment analysis, Integrated Pharmacology and Efficacy Testing Model (InPETM) drug analysis, drug-likeness evaluation, key gene screening, Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, molecular docking, and molecular dynamics simulations were performed. RESULTS A total of 1969 DEGs were identified and enriched in psoriasis-related pathways, including the TNF signaling pathway. Four core herbs (Bai Zhu, Gan Cao, Huang Qi, Ku Shen) and four key active compounds (Succinic Acid, Quercetin, Linoleic Acid, Kaempferol) were screened. Key genes (IL6, IL1B, MMP9, JUN) targeted by these compounds were jointly enriched in immune-related signaling pathways, such as T-cell receptor signaling pathway, and correlated with differentially infiltrated immune cell subsets, including activated CD4⁺ memory T cells and M1 macrophages. Molecular docking and molecular dynamics simulations suggested favorable and relatively stable binding interactions between Quercetin/Kaempferol and proteins encoded by MMP9, IL6, and IL1B. CONCLUSION Core herbs and their key active compounds, especially Quercetin and Kaempferol, may be associated with potential anti-psoriatic effects through interactions with IL6, IL1B, MMP9, and JUN, and their involvement in immune, inflammatory, and epidermal proliferation-related pathways.