Integrative network pharmacology and genetic evidence identifies NFKB1 as a predicted target of Terpinen-4-ol in psoriasis

Terpinen-4-ol (T4OL), a tea tree oil component, has anti‑inflammatory effects, but its psoriasis mechanism is unclear. We predicted T4OL targets via SEA, SuperPred, and TargetNet, and identified DEGs from GSE41662. Overlapping targets were subjected to functional enrichment, and PPI network construction. Mendelian randomization assessed causal relationships between core targets and psoriasis. We identified 159 T4OL targets, of which 42 overlapped with psoriasis DEGs. Enrichment highlighted inflammation and steroid metabolism. PPI network revealed 13 hub genes, with NFKB1 as a psoriasis risk gene. Colocalization supported shared causal variants for NFKB1 expression and psoriasis susceptibility. GSEA showed that higher NFKB1 expression correlated with reduced interferon and IL6‑JAK‑STAT3 signaling. Molecular docking and MD simulation predicted stable binding between T4OL and NFKB1. Collectively, these computational analyzes support NFKB1 as a potential T4OL target in psoriasis, but the findings are hypothesis‑generating and require experimental validation.