Network pharmacology-based investigation of the therapeutic effects and molecular mechanisms of oxymatrine in psoriasis

Introduction Psoriasis is a common chronic inflammatory skin disease with complex pathogenesis, and current therapeutic agents have certain limitations. Oxymatrine (OMT), the primary active component of the traditional Chinese herb *Sophora flavescens*, possesses multiple pharmacological effects including anti-inflammation and anti-proliferation, but its molecular mechanism against psoriasis remains incompletely elucidated. This study systematically dissected the “component-target-pathway” regulatory network of OMT against psoriasis using a network pharmacology approach to predict its underlying mechanisms, which were further validated via clinical specimen analysis and in vitro cell experiments. Methods OMT targets were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and literature mining, while psoriasis-related targets were obtained from 5 databases including GeneCards. After target mapping, drug-core target and protein-protein interaction (PPI) networks were constructed, and core targets including EGFR, AKT1, JAK2, and BCL2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, molecular docking, and 100 ns molecular dynamics (MD) simulations were conducted. Clinical validation was carried out in patients receiving 8 weeks of OMT treatment. HaCaT keratinocytes were divided into control, M5 cytokine cocktail-induced model, methotrexate (MTX) positive control, and OMT intervention groups for in vitro experiments. Results Enrichment analyses revealed significant enrichment in inflammatory response regulation, apoptotic signaling, and multiple JAK/STAT-related pathways. OMT exhibited favorable binding affinities to core targets such as EGFR, JAK1, JAK2, and STAT3. Notably, OMT-JAK1 and OMT-STAT3 complexes demonstrated excellent thermodynamic stability as validated by MD simulations. Clinically, patients’ **Psoriasis Area and Severity Index (PASI)** scores were significantly reduced, lesion histopathology was markedly improved, and aberrant EGFR-JAK/STAT and apoptosis-related molecule expression was significantly reversed. In vitro, OMT significantly inhibited M5-induced EGFR-JAK/STAT phosphorylation and activation, and restored apoptotic balance. Discussion These findings suggest that OMT exerts therapeutic effects against psoriasis by inhibiting EGFR phosphorylation, upregulating SOCS1, thereby suppressing excessive JAK/STAT signaling activation, modulating apoptosis-related protein expression, and ultimately promoting keratinocyte apoptosis while inhibiting their proliferation and inflammatory responses. This study provides experimental evidence for the clinical application of OMT in psoriasis treatment.