In vitro transcriptomics and molecular dynamics reveal palmatine as a topical candidate against psoriasis via targeting LCK to co-regulate NF-κB and Wnt signaling pathways

Psoriasis is a chronic inflammatory skin disorder characterised by immune dysregulation and aberrant keratinocyte hyperproliferation. Traditional Chinese medicine (TCM) formulae are widely used to alleviate psoriatic symptoms; however, their complex chemical compositions have long impeded the identification of core bioactive constituents. This study aimed to screen for anti‑psoriatic components from two representative TCM formulae using network pharmacology, and to further validate the therapeutic efficacy and molecular mechanism of palmatine—a major alkaloid derived from Phellodendron chinense—against psoriasis. Network pharmacology was employed to predict the potential targets of the primary constituents of P. chinense, which were then intersected with psoriasis‑associated genes retrieved from the OMIM (Online Mendelian Inheritance in Man) and GeneCards databases. An in vitro psoriasis‑like model was established by stimulating HaCaT cells with IL‑17A. Cell viability assay, cell cycle analysis, and Western blotting were performed to evaluate the pharmacological effects of palmatine. Transcriptomic profiling combined with bioinformatics analysis was used to identify key signalling pathways. Molecular docking and 100‑ns molecular dynamics (MD) simulations were conducted to screen and validate the core target proteins. Palmatine shared a substantial number of targets with psoriasis‑related genes and effectively reversed IL‑17A‑induced S‑phase arrest in HaCaT cells. A total of 736 differentially expressed genes were identified, with significant enrichment in the NF‑κB and Wnt signalling pathways. Molecular docking revealed that palmatine bound tightly to IKBKB, LYN, and LCK, and MD simulations further confirmed that the LCK–palmatine complex exhibited favourable structural stability throughout the 100‑ns trajectory. Palmatine exhibits considerable anti‑psoriatic activity in the in vitro setting, potentially through targeting LCK and modulating the NF‑κB and Wnt signalling pathway. This study provides a novel candidate compound and a precise molecular target for the research and development of anti‑psoriatic therapeutics.