Palmatine as a topical candidate for psoriasis targeting LCK to inhibit NF-κB signaling with computational prediction of Wnt pathway involvement

Abstract

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 used to construct a drug-component-target-disease network, identifying palmatine as the principal anti-psoriatic constituent of P. chinense. An IL-17A-induced HaCaT cell model was established. Cell viability was measured to determine working concentrations, and psoriasis-associated markers were quantified by RT-qPCR. Transcriptomic profiling with bioinformatics analysis identified key signalling pathways. Molecular docking and 100-ns MD simulations prioritized core targets, and CETSA validated target engagement. NF-κB activation was assessed by Western blotting. Palmatine shared a substantial number of targets with psoriasis-related genes. In IL-17A-stimulated HaCaT cells, palmatine significantly reversed the upregulation of psoriasis-associated markers and inhibited NF-κB activation, with efficacy comparable to methotrexate. Transcriptomic analysis identified 736 differentially expressed genes enriched in the NF-κB and Wnt signalling pathways, with Wnt involvement computationally predicted. Molecular docking and MD simulations prioritised LCK as the core target, and CETSA further confirmed that palmatine preferentially engaged LCK over LYN in intact cells. Palmatine exhibits considerable anti‑psoriatic activity in the in vitro setting, potentially through targeting LCK and modulating the NF‑κB signalling pathway. This study provides a novel candidate compound and a precise molecular target for the research and development of anti‑psoriatic therapeutics.

The authors' abstract, as published at the source. Scientific Reports, 2026 · DOI ↗