Anti-Psoriatic Pharmacodynamic Material Basis of Dictamni Cortex Based on Transdermal Constituents Group.

Background: Psoriasis is a chronic inflammatory skin disorder for which topical medications are the preferred treatment option. However, current therapies are limited by adverse reactions, drug resistance, and economic burdens. Dictamni Cortex (DC; the root bark of Dictamnus dasycarpus Turcz.) has a long history in the treatment of psoriasis, with its transdermal bioactive constituents serving as the pharmacodynamic foundation for topical anti-psoriatic therapy. Methods: Building on the separation of DC's chemical constituents, this study integrated ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and network pharmacology, along with activity verification, to investigate the anti-psoriatic active components among the transdermal constituents of DC. Results: Forty-one chemical constituents were characterized in DC, including 26 transdermally permeable compounds, predominantly alkaloids and limonoids. Network pharmacological analysis revealed core targets, including MMP9 and TLR4, as well as multiple pathways related to inflammatory and immune responses. Molecular docking studies identified dictamnine, jangomolide, rutaevin, and other key transdermal constituents that exhibited high binding affinity to core targets. In vitro validation showed that these compounds significantly suppressed cellular proliferation (p < 0.05) and downregulated Ki67 mRNA expression (p < 0.05) in the psoriasis-like HaCaT cell model. Concurrently, they significantly reduced secretion of key pro-inflammatory cytokines, including IL-17A, IL-22, IL-1β, IL-6, and IL-8 (p < 0.05). Comprehensive comparative analyses confirmed that dictamnine exhibited ideal anti-psoriatic efficacy. Conclusions: These results provide a pharmacological substance basis for the development of external preparations of DC for treating psoriasis and provide novel research concepts for investigating the pharmacodynamic material basis of Traditional Chinese Medicine topical drugs.